The Official Patient's Sourcebook on Melanoma: A Revised and Updated Directory for the Internet Age

THE OFFICIAL PATIENT’S SOURCEBOOK on ELANOMA J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS ii...

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THE OFFICIAL PATIENT’S SOURCEBOOK

on

ELANOMA

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The Official Patient’s Sourcebook on Melanoma: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83477-6 1. Melanoma-Popular works. I. Title.

iii

Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of melanoma.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to melanoma. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to melanoma, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Merkel Cell Carcinoma

·

The Official Patient's Sourcebook on Skin Cancer

To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 4

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON MELANOMA: GUIDELINES .............. 9

Overview............................................................................................................... 9 What Is Melanoma?............................................................................................ 11 Stage Information ............................................................................................... 12 How Is Melanoma Treated? ............................................................................... 13 Treatment by Stage............................................................................................. 15 To Learn More .................................................................................................... 17 About PDQ......................................................................................................... 18 More Guideline Sources ..................................................................................... 19 Vocabulary Builder............................................................................................. 33

CHAPTER 2. SEEKING GUIDANCE ....................................................... 37

Overview............................................................................................................. 37 Associations and Melanoma ............................................................................... 37 Finding More Associations................................................................................. 42 Cancer Support Groups...................................................................................... 44 The Cancer Information Service ......................................................................... 46 Finding Cancer Resources in Your Community................................................ 48 Finding Doctors Who Specialize in Cancer Care ............................................... 52 Selecting Your Doctor ........................................................................................ 54 Working with Your Doctor ................................................................................ 56 Finding a Cancer Treatment Facility ................................................................. 57 Additional Cancer Support Information ............................................................ 59 Vocabulary Builder............................................................................................. 59

CHAPTER 3. CLINICAL TRIALS AND MELANOMA .............................. 61

Overview............................................................................................................. 61 Recent Trials on Melanoma................................................................................ 64 Benefits and Risks............................................................................................... 94 Clinical Trials and Insurance Coverage ............................................................. 97 Clinical Trials and Medicare Coverage ............................................................ 100 Increasing the Likelihood of Insurance Coverage for Trials ............................. 101 If Your Insurance Claim Is Denied after the Trial Has Begun ........................ 103 Government Initiatives to Expand Insurance Coverage for Trials .................. 106 Keeping Current on Clinical Trials.................................................................. 107 General References............................................................................................ 108

viii Contents

Vocabulary Builder........................................................................................... 109

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL................................................ 113 CHAPTER 4. STUDIES ON MELANOMA .............................................. 115

Overview........................................................................................................... 115 The Combined Health Information Database ................................................... 115 Federally Funded Research on Melanoma........................................................ 125 The National Library of Medicine: PubMed .................................................... 140 Vocabulary Builder........................................................................................... 159

CHAPTER 5. PATENTS ON MELANOMA ............................................ 167

Overview........................................................................................................... 167 Patents on Melanoma ....................................................................................... 168 Patent Applications on Melanoma ................................................................... 183 Keeping Current ............................................................................................... 197 Vocabulary Builder........................................................................................... 197

CHAPTER 6. BOOKS ON MELANOMA ................................................ 201

Overview........................................................................................................... 201 Book Summaries: Federal Agencies .................................................................. 201 The National Library of Medicine Book Index ................................................. 204 Chapters on Melanoma..................................................................................... 206 General Home References ................................................................................. 216 Vocabulary Builder........................................................................................... 217

CHAPTER 7. MULTIMEDIA ON MELANOMA ..................................... 219

Overview........................................................................................................... 219 Video Recordings .............................................................................................. 219 Bibliography: Multimedia on Melanoma ......................................................... 221 Vocabulary Builder........................................................................................... 224

CHAPTER 8. PERIODICALS AND NEWS ON MELANOMA .................. 225

Overview........................................................................................................... 225 News Services & Press Releases ....................................................................... 225 Newsletter Articles ........................................................................................... 236 Academic Periodicals Covering Melanoma ...................................................... 238 Vocabulary Builder........................................................................................... 240

CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 243

Overview........................................................................................................... 243 NIH Guidelines................................................................................................. 243 What Is Melanoma?.......................................................................................... 244 Cellular Classification ...................................................................................... 245 Stage Information ............................................................................................. 246 Clark’s Classification (Level of Invasion) ......................................................... 247 TNM Definitions.............................................................................................. 247 Clinical Staging ................................................................................................ 248

Contents

ix

Pathologic Staging............................................................................................ 250 Treatment Option Overview ............................................................................ 251 NIH Databases.................................................................................................. 276 Other Commercial Databases ........................................................................... 289 The Genome Project and Melanoma................................................................. 290 Specialized References....................................................................................... 294 Vocabulary Builder........................................................................................... 295

CHAPTER 10. DISSERTATIONS ON MELANOMA................................ 299

Overview........................................................................................................... 299 Dissertations on Melanoma.............................................................................. 299 Keeping Current ............................................................................................... 301 Vocabulary Builder........................................................................................... 301

PART III. APPENDICES .................................................. 303 APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 305

Overview........................................................................................................... 305 Your Medications: The Basics .......................................................................... 306 Learning More about Your Medications .......................................................... 307 Commercial Databases...................................................................................... 310 Drug Development and Approval .................................................................... 311 Understanding the Approval Process for New Cancer Drugs......................... 312 The Role of the Federal Drug Administration (FDA)...................................... 313 Getting Drugs to Patients Who Need Them .................................................... 316 Contraindications and Interactions (Hidden Dangers) ................................... 318 A Final Warning .............................................................................................. 319 General References............................................................................................ 320 Vocabulary Builder........................................................................................... 321

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 323

Overview........................................................................................................... 323 What Is CAM? ................................................................................................. 324 What Are the Domains of Alternative Medicine?............................................ 325 Finding CAM References on Melanoma .......................................................... 330 Additional Web Resources................................................................................ 340 General References............................................................................................ 348 Vocabulary Builder........................................................................................... 350

APPENDIX C. RESEARCHING NUTRITION ......................................... 353

Overview........................................................................................................... 353 Food and Nutrition: General Principles........................................................... 354 Finding Studies on Melanoma ......................................................................... 358 Federal Resources on Nutrition........................................................................ 362 Additional Web Resources................................................................................ 363 Vocabulary Builder........................................................................................... 364

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 367

Overview........................................................................................................... 367

x

Contents

Preparation ....................................................................................................... 367 Finding a Local Medical Library ...................................................................... 368 Medical Libraries Open to the Public............................................................... 368

APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 375

Overview........................................................................................................... 375 Your Rights as a Patient................................................................................... 375 Patient Responsibilities .................................................................................... 379 Choosing an Insurance Plan............................................................................. 380 Medicare and Medicaid .................................................................................... 382 Financial Assistance for Cancer Care............................................................... 385 NORD’s Medication Assistance Programs ..................................................... 388 Additional Resources ........................................................................................ 389 Vocabulary Builder........................................................................................... 390

ONLINE GLOSSARIES.................................................... 391 Online Dictionary Directories.......................................................................... 396

MELANOMA GLOSSARY .............................................. 397 General Dictionaries and Glossaries ................................................................ 420

INDEX................................................................................... 422

Introduction

1

INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 Adapted from the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

2

Melanoma

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The Official Patient’s Sourcebook on Melanoma has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to melanoma, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on melanoma. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on melanoma should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate

Introduction

3

options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching melanoma (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to melanoma. It also gives you sources of information that can help you find a doctor in your local area specializing in treating melanoma. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with melanoma. Part II moves on to advanced research dedicated to melanoma. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on melanoma. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with melanoma or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with melanoma. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with melanoma.

Scope While this sourcebook covers melanoma, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that melanoma is often considered a synonym or a condition closely related to the following: ·

Malignant Melanoma

·

Melanoblastoma

·

Melanocarcinoma

4

Melanoma

·

Melanoepithelioma

·

Melanoma

·

Melanosarcoma

·

Melanoscirrhus

·

Melanotic Carcinoma

·

Nevus Pigmentosa

·

Skin Cancer- Melanoma

In addition to synonyms and related conditions, physicians may refer to melanoma using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for melanoma:4 ·

172.9 melanoma of skin, site unspecified

·

172.9 melanoma of the skin, site unspecified

For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to melanoma. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful.

This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

4

Introduction

5

As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with melanoma will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with melanoma is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of melanoma, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

7

PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on melanoma. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of melanoma to you or even given you a pamphlet or brochure describing melanoma. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

CHAPTER 1. GUIDELINES

THE

ESSENTIALS

ON

9

MELANOMA:

Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines on melanoma. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on melanoma can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on melanoma. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

5

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Melanoma

There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with melanoma and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Cancer Institute (NCI); guidelines available at http://cancernet.nci.nih.gov/pdq/pdq_treatment.shtml

Among the above, the National Cancer Institute (NCI) is particularly noteworthy. The NCI coordinates the National Cancer Program, which conducts and supports research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.6 Specifically, the Institute: ·

Supports and coordinates research projects conducted by universities, hospitals, research foundations, and businesses throughout this country and abroad through research grants and cooperative agreements.

·

Conducts research in its own laboratories and clinics.

·

Supports education and training in fundamental sciences and clinical disciplines for participation in basic and clinical research programs and treatment programs relating to cancer through career awards, training grants, and fellowships.

·

Supports research projects in cancer control.

·

Supports a national network of cancer centers.

·

Collaborates with voluntary organizations and other national and foreign institutions engaged in cancer research and training activities.

·

Encourages and coordinates cancer research by industrial concerns where such concerns evidence a particular capability for programmatic research.

·

Collects and disseminates information on cancer.

This paragraph has been adapted from the NCI: http://www.nci.nih.gov/. “Adapted” signifies that a passage has been reproduced exactly or slightly edited for this book.

6

Guidelines 11

·

Supports construction of laboratories, clinics, and related facilities necessary for cancer research through the award of construction grants.

The NCI, established under the National Cancer Act of 1937, is the Federal Government’s principal agency for cancer research and training. The National Cancer Act of 1971 broadened the scope and responsibilities of the NCI and created the National Cancer Program. Over the years, legislative amendments have maintained the NCI authorities and responsibilities and added new information dissemination mandates as well as a requirement to assess the incorporation of state-of-the-art cancer treatments into clinical practice. Information dissemination is made possible through the NCI Online at www.cancer.gov. Cancer.gov offers to the public and physicians up-to-date information on the latest cancer research, current and upcoming clinical trials, statistics, research programs, and research funding. The following patient guideline was recently published by the NCI on melanoma.

What Is Melanoma?7 Melanoma is a disease of the skin in which cancer (malignant) cells are found in the cells that color the skin (melanocytes). Melanoma usually occurs in adults, but it may occasionally be found in children and adolescents. The skin protects the body against heat, light, infection, and injury. It is made up of two main layers: the epidermis (the top layer) and dermis (the inner layer). Melanocytes are found in the epidermis and they contain melanin, which gives the skin its color. Melanoma is sometimes called cutaneous melanoma or malignant melanoma. Melanoma is a more serious type of cancer than the more common skin cancers, basal cell cancer or squamous cell cancer, which begin in the basal or squamous cells of the epidermis. Melanoma can spread (metastasize) quickly to other parts of the body through the lymph system or through the blood. (Lymph nodes are small, bean-shaped structures that are found throughout the body; they produce and store infection-fighting cells.) A doctor should be seen if a person has any of the following warning signs of melanoma: change in the size, shape, or color of a mole; oozing or bleeding from a mole; or a mole that feels itchy, The following guidelines appeared on the NCI Web site on Aug. 26, 2002. The text was last modified in August 2002. The text has been adapted for this sourcebook.

7

12 Melanoma

hard, lumpy, swollen, or tender to the touch. Melanoma can also appear on the body as a new mole. Men most often get melanoma on the trunk (the area of the body between the shoulders and hips) or on the head or neck; women most often get melanoma on the arms and legs. If there are signs of skin cancer, the doctor will examine the skin carefully. If a mole or pigmented area doesn’t look normal, the doctor will cut it out (called local excision) and look at it under the microscope to see if it contains cancer. This is usually done in a doctor’s office. It is important that this biopsy is done correctly.

Stage Information Once melanoma is found, more tests will be done to find out if cancer cells have spread to other parts of the body. This is called staging. A doctor needs to know the stage of the disease to plan treatment. The following stages are used for melanoma: Stage 0 In stage 0 melanoma, the abnormal cells are found only in the outer layer of skin cells and do not invade deeper tissues.

Stage I Cancer is found in the outer layer of the skin (epidermis) and/or the upper part of the inner layer of skin (dermis), but it has not spread to nearby lymph nodes. The tumor is less than 1.5 millimeters (1/16 of an inch) thick. Stage II The tumor is 1.5 millimeters to 4 millimeters (less than 1/6 of an inch) thick. It has spread to the lower part of the inner layer of skin (dermis), but not into the tissue below the skin or into nearby lymph nodes.

Guidelines 13

Stage III The tumor may be larger or smaller than 4 millimeters thick, may have spread to lower layers of the skin, may have additional tumor growths within 1 inch of the original tumor (satellite tumors), may have spread to surrounding lymph nodes, and may be actively spreading to nearby areas of the body. Stage IV The tumor has spread to other organs or to lymph nodes far away from the original tumor.

Recurrent Recurrent disease means that the cancer has come back (recurred) after it has been treated. It may come back in the original site or in another part of the body.

How Is Melanoma Treated? There are treatments for all patients with melanoma. Four kinds of treatments are used: ·

Surgery (taking out the cancer in an operation)

·

Chemotherapy (using drugs to kill cancer cells)

·

Radiation therapy (using high-dose x-rays or other high-energy rays to kill cancer cells)

·

Biological therapy (using the body’s immune system to fight cancer)

Surgery Surgery is the primary treatment of all stages of melanoma. The doctor may take out the melanoma using one of the following operations: ·

Conservative re-excision is an operation to take out any cancer that remains following biopsy, along with a small amount of skin around it (usually less than one-half of an inch).

14 Melanoma

·

Wide surgical excision takes out the cancer and some of the skin around the tumor.

·

Skin may have to be taken from another area of the body and put on the place where the cancer has been taken out. This is called grafting. Chemotherapy

Chemotherapy uses drugs to kill cancer cells. Chemotherapy may be taken by pill, or it may be put into the body by a needle in the vein or muscle. Chemotherapy is called a systemic treatment because the drugs enter the bloodstream, travel through the body, and can kill cancer cells throughout the body. If the melanoma occurs on an arm or leg, chemotherapy may be given with a technique called isolated arterial perfusion. In this method, chemotherapy drugs are put directly into the bloodstream of the arm or leg where the melanoma is found. This allows most of the drug to reach the tumor directly. However, chemotherapy alone has not been shown to be effective in treating melanoma. Clinical trials are being done to find chemotherapy drugs that are effective. If a doctor removes all the cancer that can be seen at the time of the operation, a patient may be given chemotherapy after surgery to kill any cancer cells that are left. Chemotherapy given after an operation to a person who has no cancer cells that can be found is called adjuvant chemotherapy. Adjuvant therapy has been shown to be effective for patients whose disease has spread to their lymph nodes. Clinical trials are being done to find adjuvant chemotherapy drugs that are effective. Radiation Therapy Radiation therapy uses high-energy x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external radiation therapy) or from putting materials that produce radiation (radioisotopes) through thin plastic tubes in the area where the cancer cells are found (internal radiation therapy). Biological Therapy Biological therapy tries to get the body to fight cancer. It uses materials made by the body or made in a laboratory to boost, direct, or restore the body’s natural defenses against disease. Biological treatment is sometimes called

Guidelines 15

biological response modifier (BRM) therapy or immunotherapy. Clinical trials are being done to find biological therapies that are effective.

Treatment by Stage Treatment of melanoma depends on the type of the disease, the stage of disease, and the patient’s age and general health. Standard treatment may be considered because of its effectiveness in patients in past studies, or participation in a clinical trial may be considered. Surgery is currently the only standard treatment of melanoma. Clinical trials are designed to find better ways to treat cancer patients. Clinical trials are ongoing in most parts of the country for most stages of melanoma. To learn more about clinical trials, call the Cancer Information Service at 1-800-4CANCER (1-800-422-6237); TTY at 1-800-332-8615.

Stage 0 Melanoma Treatment may be the following: ·

Minor surgery to remove all of the tumor and some of the surrounding tissue.

Stage I Melanoma Treatment may be one of the following: ·

Surgery to remove all of the tumor, including as much as 2 centimeters of the surrounding tissue. Skin grafting may be done to cover the wound. Stage II Melanoma

Treatment may be one of the following: ·

Surgery to remove all of the tumor, including as much as 3 centimeters of the surrounding tissue. Skin grafting may be done to cover the wound. Removal of nearby lymph nodes may also be performed.

·

A clinical trial of surgery to remove all of the tumor, including as much as 3 centimeters of the surrounding tissue followed by biological therapy.

16 Melanoma

·

A clinical trial of surgery including removal of regional lymph nodes followed by adjuvant chemotherapy, adjuvant biological therapy, or immunological therapy.

Stage III Melanoma Treatment may be one of the following: ·

Surgery to remove all of the tumor, including as much as 3 centimeters of the surrounding tissue. Skin grafting may be done to cover the wound. Removal of nearby lymph nodes may also be performed.

·

A clinical trial of surgery to remove all of the tumor, including as much as 3 centimeters of the surrounding tissue followed by biological therapy.

·

A clinical trial of surgery including removal of regional lymph nodes followed by adjuvant chemotherapy, adjuvant biological therapy, or immunological therapy.

Stage IV Melanoma Treatment may be one of the following: ·

Surgery to remove lymph nodes that contain cancer or tumors that have spread (metastasized) to other areas of the body.

·

Radiation therapy to relieve symptoms caused by the cancer.

·

A clinical trial of systemic chemotherapy and/or biological therapy.

·

A clinical trial of radiation therapy to relieve symptoms caused by the cancer.

·

A clinical trial of surgery to remove all of the cancer.

Recurrent Melanoma Treatment depends on many factors, such as the treatment the patient received before, and where the cancer came back. Treatment may be one of the following: ·

Surgery to remove the tumor.

·

Radiation therapy to relieve symptoms caused by the cancer.

Guidelines 17

·

A clinical trial of biological therapy or chemotherapy to relieve symptoms caused by the cancer.

·

Biological therapy to relieve symptoms caused by the cancer.

·

Heated chemotherapy drugs injected directly into the cancer.

To Learn More Call For more information, U.S. residents may call the National Cancer Institute’s (NCI’s) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-4226237), Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-ofhearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.

Web Sites and Organizations The NCI’s Cancer.gov Web site (http://cancer.gov) provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. There are also many other places where people can get materials and information about cancer treatment and services. Local hospitals may have information on local and regional agencies that offer information about finances, getting to and from treatment, receiving care at home, and dealing with problems associated with cancer treatment. Publications The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator (https://cissecure.nci.nih.gov/ncipubs). These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-8004-CANCER (1-800-422-6237), TTY at 1-800-332-8615.

18 Melanoma

LiveHelp The NCI’s LiveHelp service, a program available on several of the Institute’s Web sites, provides Internet users with the ability to chat online with an Information Specialist. The service is available from Monday - Friday 9:00 AM - 10:00 PM Eastern Time. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer. Write For more information from the NCI, please write to this address: National Cancer Institute Office of Communications 31 Center Drive, MSC 2580 Bethesda, MD 20892-2580

About PDQ PDQ Is a Comprehensive Cancer Database Available on Cancer.gov PDQ is the National Cancer Institute’s (NCI’s) comprehensive cancer information database. Most of the information contained in PDQ is available online at Cancer.gov (http://cancer.gov), the NCI’s Web site. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government’s focal point for biomedical research. PDQ Contains Cancer Information Summaries The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries are available in two versions. The health professional versions provide detailed information written in technical language. The patient versions are written in easy-tounderstand, non-technical language. Both versions provide current and accurate cancer information. The PDQ cancer information summaries are developed by cancer experts and reviewed regularly. Editorial Boards made up of experts in oncology and related specialties are responsible for writing and maintaining the cancer

Guidelines 19

information summaries. The summaries are reviewed regularly and changes are made as new information becomes available. The date on each summary (“Date Last Modified”) indicates the time of the most recent change.

PDQ Contains Information on Clinical Trials Before starting treatment, patients may want to think about taking part in a clinical trial. A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about new treatments, the risks involved, and how well they do or do not work. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become “standard.” Listings of clinical trials are included in PDQ and are available online at Cancer.gov (http://cancer.gov/clinical_trials). Descriptions of the trials are available in health professional and patient versions. Many cancer doctors who take part in clinical trials are also listed in PDQ. For more information, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237); TTY at 1-800-332-8615.

More Guideline Sources The guideline above on melanoma is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to melanoma. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with melanoma. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patient-

20 Melanoma

oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following as being relevant to melanoma: ·

Guides On Melanoma Malignant melanoma http://www.nlm.nih.gov/medlineplus/ency/article/001442.htm Melanoma http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm

Within the health topic page dedicated to melanoma, the following was recently recommended to patients: ·

General/Overviews Malignant Melanoma Source: American Academy of Dermatology http://www.aad.org/pamphlets/malmel.html Melanoma http://www.nlm.nih.gov/medlineplus/tutorials/melanomaloader.ht ml

·

Diagnosis/Symptoms ABCDs of Melanoma Detection Source: American Academy of Dermatology http://www.aad.org/SkinCancerNews/WhatIsSkinCancer/ABCDM el.html How is Melanoma Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_me lanoma_diagnosed_50.asp How is Melanoma Staged? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_me lanoma_staged_50.asp

Guidelines 21

·

Treatment How Is Melanoma Skin Cancer Treated? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_2_4x_how_is_me lanoma_skin_cancer_treated_50.asp Intraocular (Eye) Melanoma (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancer_information/doc_pdq.aspx?version= patient&viewid=49d0b28a-ea54-4cd3-b017-64e34a2145ae Melanoma (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancer_information/doc_pdq.aspx?version= patient&viewid=7763f63a-fc70-4792-a33f-bf1855968725

·

Coping Coping With Melanoma Source: Skin Cancer Foundation http://www.skincancer.org/melanoma/coping.html

·

Specific Conditions/Aspects "Hidden" Melanomas Source: American Academy of Dermatology http://www.skincarephysicians.com/melanomanet/MelanomaRisk_ november.htm About Choroidal Melanoma Source: Johns Hopkins University http://www.jhu.edu/wctb/coms/booklet/book2.htm Atypical Nevus Source: American Academy of Dermatology http://www.aad.org/pamphlets/anevus.html What You Need to Know about Moles and Dysplastic Nevi Source: National Cancer Institute http://www.cancer.gov/cancer_information/doc_wyntk.aspx?viewi d=c3508072-3797-40c7-848b-7bbbe9ce16d4

22 Melanoma

·

From the National Institutes of Health What You Need to Know about Melanoma Source: National Cancer Institute http://www.cancer.gov/cancer_information/doc_wyntk.aspx?viewi d=8f3e1c39-1ba0-4a7e-9088-e03c592c5395

·

Latest News Computer Images Provide Better Melanoma Detection Source: 11/21/2002, Reuters Health http://www.nlm.nih.gov/medlineplus/news/fullstory_10537.html Immune System Cells May Help Prevent Tumor Growth Source: 11/11/2002, Reuters Health http://www.nlm.nih.gov/medlineplus/news/fullstory_10305.html New Approach to Replacing Immune Cells Shrinks Tumors in Patients with Melanoma Source: 09/19/2002, National Cancer Institute http://www.nih.gov/news/pr/sep2002/nci-19.htm

·

Organizations American Academy of Dermatology http://www.aad.org/ American Cancer Society http://www.cancer.org/ National Cancer Institute http://www.cancer.gov/ Skin Cancer Foundation http://www.skincancer.org/

·

Pictures/Diagrams Skin Lesions Source: American Academy of Dermatology http://www.skincarephysicians.com/melanomanet/skin_lesions.ht m

Guidelines 23

·

Prevention/Screening Can Melanoma Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_can_melan oma_be_prevented_50.asp Melanoma Cancer Questionnaire Source: Harvard Center for Cancer Prevention http://www.yourcancerrisk.harvard.edu/hccpquiz.pl?func=d_start& cancer_list=Melanoma Self-Examination for Melanoma Source: American Academy of Dermatology http://www.skincarephysicians.com/melanomanet/self_exam.htm What Are The Risk Factors for Melanoma? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_what_are_t he_risk_factors_for_melanoma_50.asp

·

Research Cancer Research: Killing Tumor Cells With Anthrax-based Immunotoxin Source: National Institute of Dental and Craniofacial Research http://www.nidcr.nih.gov/news/inside_scoop_cancer_rsch.asp Do We Know What Causes Melanoma? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_2x_do_we_kn ow_what_causes_melanoma_50.asp Individuals' Risk of Melanoma Increases With Time Outdoors, Especially in High-Sunlight Areas Source: National Cancer Institute http://newscenter.cancer.gov/pressreleases/individualmelanoma.ht ml New Approach to Replacing Immune Cells Shrinks Tumors in Patients with Melanoma Source: National Cancer Institute http://www.nih.gov/news/pr/sep2002/nci-19.htm What's New in Melanoma Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new _in_melanoma_research_and_treatment_50.asp

24 Melanoma

·

Statistics SEER Cancer Statistics Review 1973-1999: Melanomas of Skin Source: img src='/medlineplus/images/linkpdf.gif' width='100' height='17' border=0 alt='Links to PDF File'> (National Cancer Institute http://seer.cancer.gov/csr/1973_1999/melanoma.pdf What Are The Key Statistics for Melanoma Skin Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_t he_key_statistics_for_melanoma_50.asp

If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.

The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on melanoma and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

Guide to Skin Cancers and Precancers, A Source: New York, NY: Skin Cancer Foundation. 2002. 18 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. Website: www.skincancer.org. Price: Contact for current pricing; bulk orders available. Item No. BR-19.

Guidelines 25

Summary: This booklet provides the general public with information on skin precancers and cancers. Actinic keratosis (AK), or solar keratosis, is the most common type of precancerous skin lesion. AKs most often appear on skin surfaces that have been frequently exposed to the sun or to artificial sources of ultraviolet light. They range in size from 1 millimeter to 1 inch in diameter. AKs usually appear as small crusty, scaly, or crumbly bumps or horns that are dry and rough to the touch. Untreated AKs may develop into squamous cell carcinoma (SCC). Treatment options for AKs include cryosurgery; curettage and desiccation; topical medications such as 5-fluorouracil cream or solution, hyaluronic acid/diclofenac, and imiquimod cream; chemical peeling; laser surgery; and photodynamic therapy. The most common skin cancers are basal cell carcinoma (BCC) and SCC. Both are mainly caused by long term sun exposure, so they typically occur in areas that are exposed to the sun. Although BCCs rarely spread to vital organs, they can lead to disfigurement. SCCs have a greater chance of spreading and becoming life threatening if untreated. Treatment options for BCCs and SCCs include curettage and electrodesiccation, excisional surgery, radiation, and Mohs micrographic surgery. In addition, cryosurgery, laser surgery, and photodynamic therapy can be used to treat BCCs and SCCs. The deadliest form of skin cancer is melanoma. It is most often caused by intense, intermittent exposure to the sun, especially before age 18. Melanoma is treatable in its earliest stage, but if left untreated, it will spread to vital organs. People should check their skin every month for lesions that are asymmetrical and have border irregularity, color variability, and a diameter larger than a pencil eraser. Treatment options for melanoma discovered at an early stage include excisional surgery, Mohs micrographic surgery, and regional lymph node dissection. Approaches for treating melanoma that has spread include radiation, chemotherapy, and immunotherapy. Skin cancers can be prevented by taking appropriate sun safety measures. 18 figures. ·

Malignant Melanoma Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2001. 8 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail: [email protected]. Website: www.aad.org. Price: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have melanoma with information on its causes, symptoms, and treatment. Melanoma is a cancer of the pigment producing cells in

26 Melanoma

the skin. Although it is uncertain how all cases of melanoma develop, it is clear that excessive sun exposure, especially blistering sunburns during childhood, can promote melanoma development. Ultraviolet radiation used in indoor tanning equipment may also cause melanoma. Although anyone can get melanoma, fair skinned people who tan poorly or burn easily are at greater risk. Other risk factors include a history of sunburns, many moles, atypical moles, and close relatives who had melanoma. Melanoma usually begins on the surface of the skin where it is easily treated. Left untreated, it can grow down into the skin, ultimately reaching the blood and lymphatic vessels and spreading around the body. Melanoma is usually brown or black in color, but may be red, skin colored, or white. Melanomas slowly get larger. Diagnosis is based on a biopsy of the lesion for examination under the microscope. Treatment begins with surgical removal of the melanoma and some normal appearing skin around the growth. The depth of invasion of the growth into the skin guides further treatment. Preventive efforts include avoiding sun exposure during times of the day when the sun is the strongest, wearing a broad spectrum sunscreen and protective clothing, and performing a monthly self examination. The pamphlet includes the asymmetry, border irregularity, color, and diameter (ABCD) rules to determine if a spot on the skin is suspicious. 5 figures. ·

What Everyone Should Know About Skin Cancer Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1999. 16 p. Contact: Available from Channing L. Bete Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. E-mail: [email protected]. Price: Contact company for pricing information; available in bulk. Order Number 37259C-6-96. Summary: This illustrated booklet provides the general public with information on skin cancer. This most common form of all cancers results from the uncontrolled growth of abnormal skin cells. It is usually preventable and curable. Types of skin cancer include basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Overexposure to the sun causes most cases of skin cancer. Although anyone can get skin cancer, people with certain physical traits and lifestyles are at greater risk. Being alert to changes in the skin's color, texture, and sensation and performing a monthly skin examination are important early detection measures. Treatment methods include excisional surgery, cryosurgery, radiation therapy, topical treatments, electrosurgery, chemotherapy, Mohs surgery, and reconstructive surgery. The booklet provides tips on preventing skin cancer, answers questions about the disease, and presents sources of additional information.

Guidelines 27

·

Dysplastic Nevi and Malignant Melanoma: A Patient's Guide Source: New York, NY: Skin Cancer Foundation. 1997. 12 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. Price: Single copy free; bulk orders available at cost. Summary: This brochure provides people who have dysplastic nevi and malignant melanoma with information on recognizing the features of these skin disorders. Dysplastic nevi are unusual moles that are markers for an increased risk of melanoma, which is a form of skin cancer that often looks like an irregular, enlarging, or inflamed mole. The brochure compares the features of normal moles with those of dysplastic nevi and explains what happens if moles become malignant melanoma. The brochure also offers guidelines for people who have an increased risk of developing melanoma or a diagnosis of dysplastic nevus, including performing a monthly skin self-examination, having an annual medical examination, and avoiding or decreasing exposure to the sun. 13 figures.

·

Skin Cancer: An Undeclared Epidemic Source: Schaumburg, IL: American Academy of Dermatology. 1994. 8 p. Contact: Available from American Academy of Dermatology. P.O. Box 681069, Schaumburg, IL 60168-1069. (888) 462-3376 or (847) 330-0230. http://www.aad.org/index.html. Price: Single copy free; bulk prices available. Summary: This brochure for the general public provides information on skin cancer. It states that overexposure to sunlight is almost universally accepted by medical experts as the main cause of skin cancer and that guarding the skin against the known causes is the best prevention. The brochure suggests a method of self-examination to detect any skin changes that will ensure that all areas of the body are examined. It describes the features of actinic keratosis, a precancerous condition, as well as basal and squamous cell carcinoma and malignant melanoma. In addition, the brochure comments on various skin cancer treatments. 2 figures. 3 photographs.

·

Types and Descriptions of Skin Cancers Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. Price: Single copy free; bulk orders available at cost.

28 Melanoma

Summary: This pamphlet uses photographs and descriptive text to provide the general public with information about the features of basal and squamous cell carcinoma and malignant melanoma. Basal cell carcinomas, which are raised, translucent, pearly nodules that may crust, ulcerate, and sometimes bleed, usually occur on the face and other exposed areas of the body. Squamous cell carcinomas, which are usually raised, pink, opaque nodules or patches that frequently ulcerate in the center, most often appear on exposed areas of the body. Malignant melanomas, which are usually small brown-black or larger multicolored patches, plaques, or nodules with irregular borders, may arise in preexisting moles. In addition, the pamphlet provides examples of various precancers, including actinic keratoses, leukoplakia, and radiodermatitis. 9 figures. ·

What You Need To Know About Skin Cancer Source: New York, NY: Skin Cancer Foundation. 199x. 8 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. Website: www.skincancer.org. Price: Contact for current pricing; bulk orders available. Item No. BR-16. Summary: This pamphlet provides the general public with information on skin cancer. This form of cancer is the most common throughout the world and is almost always caused by exposure to the ultraviolet rays of the sun. Actinic keratosis is a form of precancer. Basal and squamous cell carcinomas are the two most common forms of skin cancers, and malignant melanoma is the most life threatening. The warning signs of skin cancer include a skin growth the increases in size and is pearly, translucent, tan, brown, black, pink, or multicolored; a mole that changes in color or in texture, becomes irregular, or is bigger than a pencil eraser; a spot or growth that itches, hurts, crusts, scabs, erodes, or bleeds; an open sore that lasts for more than 4 weeks; and a scaly or crusty bump that is horny, dry, and rough. The pamphlet presents examples of skin cancers and offers sun protection tips. 3 figures.

·

ABCDs of Moles and Melanomas, The Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. Website: www.skincancer.org. Price: Contact for current pricing; bulk orders available. Item No. BR-4.

Guidelines 29

Summary: This pamphlet provides the general public with information on the detection of malignant melanoma. A change in a mole or other spot on the skin may be the first sign of an early malignant melanoma or other form of skin cancer. Malignant melanoma arises in moles or in the tanning cells of the skin. People at high risk of developing malignant melanoma are those who have a family history of the disease, a previous melanoma, unusual moles on the skin, fair skin, light hair and eye color, a record of painful or blistering sunburns, and indoor occupations and outdoor recreational habits. Regular self examination is the best way to detect a malignant melanoma. Some forms of early malignant melanoma are asymmetrical, have uneven borders, are multicolored, and are larger than a pencil eraser. The pamphlet provides examples of these features. 12 figures. ·

It's Never Too Early To Stop Skin Cancer Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. Website: www.skincancer.org. Price: Contact for current pricing; bulk orders available. Item No. BR-2. Summary: This pamphlet uses a question and answer format to provide the general public with information on skin cancer. The three main types of skin cancer are basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Exposure to the ultraviolet rays of the sun is the most frequent cause of skin cancer. People at risk of developing skin cancer are those who have fair skin and those who allow themselves considerable exposure to the sun. Skin cancer in its earliest stages may appear as a discoloration of the skin. People should pay attention to any changes in the size, color, shape, or thickness of preexisting moles or other growths. A biopsy of a suspicious lesion helps a doctor determine whether the lesion is benign, precancerous, or cancerous. Common treatment methods are electrosurgery, excisional surgery, chemosurgery, cryosurgery, radiation therapy, and chemotherapy. Protective measures include avoiding unnecessary exposure to the sun; wearing tightly woven protective clothing such as sun hats, long sleeved shirts, pants, and gloves; avoiding midday exposure; and using sunscreen with a sun protection factor (SPF) of 15 or higher. The pamphlet explains what the SPF is and how to select and use sunscreen.

·

Many Faces of Malignant Melanoma, The Source: New York, NY: Skin Cancer Foundation. 199x. 6 p.

30 Melanoma

Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. Website: www.skincancer.org. Price: Contact for current pricing; bulk orders available. Item No. BR-5. Summary: This pamphlet provides health professionals and the general public with 24 examples of malignant melanoma, which were selected to represent thin, intermediate, and thick melanomas. Tumor thickness is a key indicator in predicting which malignant melanomas are curable and which are not. Malignant melanomas that are removed when they are less than three fourths of a millimeter thick are cured in almost all cases; however, progressively thicker malignant melanomas have correspondingly poorer prognoses. The first eight photographs show examples of thin, early malignant melanomas. The second eight photographs depict examples of melanomas of intermediate thickness. The final eight photographs show examples of the thickest melanomas. The pamphlet also includes a list of the risk factors for and warning signs of malignant melanoma. 24 figures.

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “melanoma” or synonyms. The following was recently posted: ·

Guidelines of care for primary cutaneous melanoma. Source: American Academy of Dermatology.; 2001 March; 8 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1967&sSearch_string=melanoma

·

Systemic adjuvant therapy for patients at high risk for recurrent melanoma. Source: Cancer Care Ontario Practice Guidelines Initiative.; 1998 May 27 (updated 2000 Sep); Various pagings http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2036&sSearch_string=melanoma

Guidelines 31

Healthfinder™ Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·

ABCD’s of Skin Cancer Summary: A general overview of three types of skin cancer-- basal cell carcinoma, squamous cell carcinoma, and melanoma are illustrated. Explains self-exam for skin cancer. Source: American Academy of Dermatology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5777

·

Congenital Nevi or Moles Summary: This information is intended to provide basic information only. It provides a general description for nevi and discusses the risk of skin cancer/melanoma associated with them. Source: Nevus Network http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2357

·

Intraocular (Eye) Melanoma (PDQ®): Treatment Summary: Treatment information for patients based on information in the PDQ summary for health professionals on the cancer type -intraocular melanoma. Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5068

32 Melanoma

·

MelanomaNet Summary: Basic facts about melanoma and its risks, prevention, and treatment. Self-examination information is provided as well as a glossary. Source: American Academy of Dermatology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6397

·

Skincarephysicians.com Summary: An index to Web pages on psoriasis, eczema, aging skin, acne, melanoma, and actinic keratoses. Source: American Academy of Dermatology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=6380

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to melanoma. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

Guidelines 33

Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

·

drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

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Family Village: http://www.familyvillage.wisc.edu/specific.htm

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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

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WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Anthrax: An infectious bacterial zoonotic disease usually acquired by ingestion of Bacillus anthracis or its spores from infected pastures by herbivores or indirectly from infected carcasses by carnivores. It is transmitted to humans usually by contact with infected animals or their discharges (agricultural a.) or with contaminated animal products (industrial a.). Anthrax is classified by primary routes of inoculation as : cutaneous, gastrointestinal, and inhalational. Called also charbon, milzbrand and splenic fever. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other

34 Melanoma

parts of the body. [NIH] Biopsy: The removal of cells or tissues for examination under a microscope. When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When an entire tumor or lesion is removed, the procedure is called an excisional biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle biopsy or fineneedle aspiration. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Cryosurgery: Treatment performed with an instrument that freezes and destroys abnormal tissues. This procedure is a form of cryotherapy. [NIH] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents, characterized in the acute stage by erythema, edema associated with a serous exudate between the cells of the epidermis (spongiosis) and an inflammatory infiltrate in the dermis, oozing and vesiculation, and crusting and scaling; and in the more chronic stages by lichenification or thickening or both, signs of excoriations, and hyperpigmentation or hypopigmentation or both. Atopic dermatitis is the most common type of dermatitis. Called also eczematous dermatitis. [EU] Electrodesiccation: The drying of tissue by a high-frequency electric current applied with a needle-shaped electrode. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other health-related event occurring in such outbreaks. [EU] Epidermis: The upper or outer layer of the two main layers of tissue that make up the skin. [NIH] Fluorouracil: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Immunotherapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also called biological

Guidelines 35

therapy or biological response modifier (BRM) therapy. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Keratosis: Any horny growth such as a wart or callus. [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Cells in the skin that produce and contain the pigment called melanin. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Oncology: The study of cancer. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Psoriasis: A chronic disease of the skin marked by red patches covered with white scales. [NIH] Radiodermatitis: A cutaneous inflammatory reaction occurring as a result of exposure to ionizing radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial

36 Melanoma

s.) or the complete range of manifestations of a disease. [EU] SPF: Sun protection factor, scale for rating the level of sunburn protection in sunscreen products. The higher the SPF, the more sunburn protection it provides. Sunscreens with an SPF value of 2 through 11 provide minimal protection against sunburns. Sunscreens with an SPF of 12 through 29 provide moderate protection, which is adequate for most people. Those with an SPF of 30 or higher provide high protection against sunburn and are sometimes recommended for people who are highly sensitive to the sun. [NIH] Squamous: Scaly, or platelike. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Sunscreen: A substance that helps protect the skin from the sun's harmful rays. Sunscreens reflect, absorb, and scatter both UVA and UVB radiation. Using lotions, creams, or gels that contain sunscreens can help protect the skin from premature aging and damage that may lead to skin cancer. [NIH] Systemic: Affecting the entire body. [NIH] Topical: On the surface of the body. [NIH]

Seeking Guidance 37

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with melanoma. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.8 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with melanoma. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Melanoma As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.9 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 9 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 8

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influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·

American Skin Association Address: American Skin Association 150 East 58th Street, 33rd Floor, New York, NY 10155-0002 Telephone: (212) 753-8260 Toll-free: (800) 499-7546 Fax: (212) 688-6547 Email: [email protected] Web Site: None Background: The American Skin Association (ASA) is a national nonprofit organization dedicated to building a network of lay people to achieve more effective prevention, treatment, and cure of skin disorders. ASA programs include generating support for skin research and providing information and education to the public regarding the skin and its disorders. ASA's mission is to identify, promote, and support research in biology of the skin, stimulate the transfer of advances in the field to clinical care of dermatology patients, and educate the community regarding diseases, symptoms, and care of the skin. To meet this goal, the Association engages in fundraising to support research and develops local chapters throughout the country. Information on a wide spectrum of skin disorders is available including 'Your Newborn's Skin and the Sun,' 'Ultraviolet Index: What You Need To Know,' 'Outdoor Sports and Your Skin,' and 'Proper Skin Care Can Make Gardening a Bed of Roses.' Founded in 1987, ASA also publishes 'SkinFacts,' a quarterly newsletter. Relevant area(s) of interest: Melanoma, Skin Cancer

·

CancerOnline Address: Telephone: (212) 753-8260 Toll-free: (800) 499-7546 Email: [email protected]

Seeking Guidance 39

Web Site: http://www.canceronline.org Background: CancerOnline is a nonprofit site on the Internet dedicated to providing individuals with cancer easy access to clinical information and offering extensive practical support and encouragement. CancerOnline collaborates with many different cancer care centers and organizations and provides original material contributed by cancer patients, caregivers, and cancer care specialists in private practice and a variety of cancer centers. CancerOnline's content is overseen by three advisory panels made up of oncologists, radiologists, and clinical care providers who want to help cancer patients become students of their disease; other cancer care specialists and providers of psychosocial support who want to encourage patients to participate actively in their treatment; and patients, survivors, and caregivers who want to help patients live with vitality and hope even in the face of a life-challenging illness. CancerOnline offers several major areas within its site including 'About CancerOnline,' 'Support and Encouragement,' 'Getting Information,' 'Participating in This Community,' and 'Special Features.' The site offers several sources of clinical information that can be accessed through a network of subject areas; practical advice before, during, and after treatment; stories from individuals who have triumphed over cancer; opportunities for affected individuals and families to contribute personal stories, creative expressions, commentaries, and questions; hints on how to obtain additional information on and off the Internet; dynamic linkage to additional web sites that provide information and support to those with particular types of cancer; and more. CancerOnline provides information and support to individuals with any type of cancer including Bladder Cancer, Breast Cancer, Colon and Rectal Cancer, Liver Cancer, Lymphoma, Ovarian Cancer, Prostate Cancer, Stomach Cancer, Uterine Cancer, Pediatric Cancers, Brain Tumors, Head and Neck Cancer, Leukemia, Lung Cancer, Melanoma, Pancreatic Cancer, Skin Cancer, Thyroid Cancer, and Rare Adult Cancers. Relevant area(s) of interest: Melanoma ·

International Cancer Alliance for Research and Education Address: International Cancer Alliance for Research and Education 4853 Cordell Avenue, Suite 11, Bethesda, MD 20814 Telephone: (301) 654-7933 Toll-free: (800) 422-7361 Fax: (301) 654-8684 Email: [email protected] Web Site: http://icare.org

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Background: The International Cancer Alliance for Research and Education (ICARE) is a nonprofit organization that provides focused information to individuals affected by cancer and their physicians on an ongoing, person-to-person basis. Cancer is a general term referring to a group of diseases characterized by uncontrolled cellular growth that may invade surrounding tissues and spread (metastasize) to other bodily tissues or organs. The different cancers may be classified based upon the organ and cell type involved, the nature of the malignancy, and the disease's clinical course. ICARE has developed several patient-centered programs through a process of collection, evaluation, and dissemination of information, bringing affected individuals into contact with physicians and scientists from around the world. The Alliance is operated by a network of scientists, clinicians, staff members, and lay volunteers, many of whom are affected by cancer themselves. The Alliance maintains the ICARE Registry, a confidential membership listing that permits ongoing dialogue between ICARE and its network members. Registry members receive a 'cancer therapy review' including a description of the specific form of cancer in question, information concerning detection and staging procedures, an overview of current treatments, a bibliography for more in-depth research, and listings of diagnostic tests, ongoing clinical trials, and second opinion centers. Registry members also receive medical, research, clinical trial, and Food and Drug Administration (FDA) updates relating to the specific form of cancer or cancer in general; regular newsletters; and access to all ICARE programs. Such programs include ICARE patient education partner centers, which provide affected individuals with access to an electronic library of cancer information and online hook-ups at the community level; private electronic support groups for individuals dealing with common types of cancer or common issues; a clinical trial matching program; and other services. ICARE provides information concerning its mission, objectives, services, and programs on its web site on the Internet. Relevant area(s) of interest: Melanoma ·

March of Dimes Birth Defects Foundation Address: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue, White Plains, NY 10605 Telephone: (914) 428-7100 Toll-free: (888) 663-4637 Fax: (914) 997-4763 Email: [email protected] Web Site: http://www.modimes.org

Seeking Guidance 41

Background: The March of Dimes Birth Defects Foundation is a national not-for- profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. Through the Campaign for Healthier Babies, the March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it produces a wide variety of printed informational materials and videos. The March of Dimes public health educational materials provide information encouraging health- enhancing behaviors that lead to a healthy pregnancy and a healthy baby. ·

Nevus Outreach, Inc Address: Nevus Outreach, Inc. 1616 Alpha Street, Lansing, MI 48910 Telephone: (517) 487-2306 Fax: (517) 374-7610 Email: [email protected] Web Site: http://www.nevus.org Background: Nevus Outreach, Inc. (NOI) is a voluntary health organization formed in 1997 by a group of parents dedicated to improving medical knowledge and treatment for individuals with giant congenital nevi and related disorders such as neurocutaneous melanosis. Giant congenital nevi are large, darkly pigmented moles or birthmarks (nevi) that are present at birth (congenital). Although such nevi may vary in size and shape and may cover any area of the body, they are often present on the chest, the shoulders, the upper back, the area covered by bathing trunks, the lower arms and legs, and/or various areas on the face and/or scalp. Individuals with giant nevi have an abnormally increased risk of developing malignant melanoma, a form of skin cancer. In addition, the nevus cells that appear on the skin may form in the central nervous system (neurocutaneous melanosis), which may cause neurological abnormalities and potentially life-threatening complications. The Nevus Outreach is committed to providing information, assistance, and support to affected individuals and family members; promoting additional research; and increasing awareness of these conditions among dermatologists and other health care professionals. NOI provides understandable information on these disorders; publishes a biannual newsletter entitled 'Nevus News'; provides periodic updates on important events and announcements; and sponsors an annual conference to enable affected individuals and family members to network with one another and to interact with medical specialists in the field. The

42 Melanoma

Nevus Outreach also acts as an advocate for affected families, helps make travel assistance arrangements for treatment, and provides referrals to other relevant organizations. In addition, the NOI has a Web site on the Internet that provides information on nevi disorders, online networking opportunities, and dynamic links to other helpful sources of information and support. ·

Skin Cancer Foundation Address: Skin Cancer Foundation 245 Fifth Avenue, Suite 1403, New York, NY 10016 Telephone: (212) 725-5176 Toll-free: (800) 754-6490 Fax: (212) 725-5751 Email: [email protected] Background: The Skin Cancer Foundation is a not-for-profit international educational health organization dedicated to providing information on detection and prevention of and support to individuals with skin cancer. The Foundation seeks to educate the public about the different forms of skin cancer and promotes and supports ongoing medical research into the causes and treatment of these diseases. Established in 1977, the Skin Cancer Foundation has a growing membership of over 130 leading physicians. The Foundation provides support for medical research and training; functions as a major resource center for the media; and works to educate the public. Programs include screening clinics, health fairs, and corporate and community wellness programs. Educational materials produced by the organization include a wide variety of brochures, posters, books, newsletters, and audio-visual materials. Relevant area(s) of interest: Melanoma, Skin Cancer

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.

The National Cancer Institute (NCI) The National Cancer Institute (NCI) has complied a list of national organizations that offer services to people with cancer and their families. To

Seeking Guidance 43

view the list, see the NCI fact sheet online at the following Web address: http://cis.nci.nih.gov/fact/8_1.htm. The name of each organization is accompanied by its contact information and a brief explanation of its services.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about melanoma. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “melanoma” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “melanoma”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “melanoma” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with melanoma. You should check back periodically with this database since it is updated every 3 months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “melanoma” (or a synonym) in the search box.

Cancer Support Groups10 People diagnosed with cancer and their families face many challenges that may leave them feeling overwhelmed, afraid, and alone. It can be difficult to cope with these challenges or to talk to even the most supportive family members and friends. Often, support groups can help people affected by cancer feel less alone and can improve their ability to deal with the uncertainties and challenges that cancer brings. Support groups give people who are affected by similar diseases an opportunity to meet and discuss ways to cope with the illness. How Can Support Groups Help? People who have been diagnosed with cancer sometimes find they need assistance coping with the emotional as well as the practical aspects of their disease. In fact, attention to the emotional burden of cancer is sometimes part of a patient’s treatment plan. Cancer support groups are designed to provide a confidential atmosphere where cancer patients or cancer survivors can discuss the challenges that accompany the illness with others who may have experienced the same challenges. For example, people gather to discuss the emotional needs created by cancer, to exchange information about their disease—including practical problems such as managing side effects or returning to work after treatment—and to share their feelings. Support groups have helped thousands of people cope with these and similar situations.

10

This section has been adapted from the NCI: http://cis.nci.nih.gov/fact/8_8.htm.

Seeking Guidance 45

Can Family Members and Friends Participate in Support Groups? Family and friends are affected when cancer touches someone they love, and they may need help in dealing with stresses such as family disruptions, financial worries, and changing roles within relationships. To help meet these needs, some support groups are designed just for family members of people diagnosed with cancer; other groups encourage families and friends to participate along with the cancer patient or cancer survivor. How Can People Find Support Groups? Many organizations offer support groups for people diagnosed with cancer and their family members or friends. The NCI fact sheet National Organizations That Offer Services to People with Cancer and Their Families lists many cancer-concerned organizations that can provide information about support groups. This fact sheet is available at http://cis.nci.nih.gov/fact/8_1.htm on the Internet, or can be ordered from the Cancer Information Service at 1–800–4–CANCER (1–800–422–6237). Some of these organizations provide information on their Web sites about contacting support groups. Doctors, nurses, or hospital social workers who work with cancer patients may also have information about support groups, such as their location, size, type, and how often they meet. Most hospitals have social services departments that provide information about cancer support programs. Additionally, many newspapers carry a special health supplement containing information about where to find support groups.

What Types of Support Groups Are Available? Several kinds of support groups are available to meet the individual needs of people at all stages of cancer treatment, from diagnosis through follow-up care. Some groups are general cancer support groups, while more specialized groups may be for teens or young adults, for family members, or for people affected by a particular disease. Support groups may be led by a professional, such as a psychiatrist, psychologist, or social worker, or by cancer patients or survivors. In addition, support groups can vary in approach, size, and how often they meet. Many groups are free, but some require a fee (people can contact their health insurance company to find out whether their plan will cover the cost). It is important for people to find an atmosphere that is comfortable and meets their individual needs.

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Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.

The Cancer Information Service11 The Cancer Information Service (CIS) is a program of the National Cancer Institute (NCI), the Nation’s lead agency for cancer research. As a resource for information and education about cancer, the CIS is a leader in helping people become active participants in their own health care by providing the latest information on cancer in understandable language. Through its network of regional offices, the CIS serves the United States, Puerto Rico, the U.S. Virgin Islands, and the Pacific Islands. For 25 years, the Cancer Information Service has provided the latest and most accurate cancer information to patients and families, the public, and health professionals by: ·

Interacting with people one-on-one through its Information Service,

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Working with organizations through its Partnership Program,

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Participating in research efforts to find the best ways to help people adopt healthier behaviors,

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Providing access to NCI information over the Internet. How Does the CIS Assist the Public?

Through the CIS toll-free telephone service (1–800–4–CANCER), callers speak with knowledgeable, caring staff who are experienced at explaining medical information in easy-to-understand terms. CIS information specialists answer calls in English and Spanish. They also provide cancer information to deaf and hard of hearing callers through the toll-free TTY number (1–800– 11

This section has been adapted from the NCI: http://cis.nci.nih.gov/fact/2_5.htm.

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332–8615). CIS staff have access to comprehensive, accurate information from the NCI on a range of cancer topics, including the most recent advances in cancer treatment. They take as much time as each caller needs, provide thorough and personalized attention, and keep all calls confidential. The CIS also provides live, online assistance to users of NCI Web sites through LiveHelp, an instant messaging service that is available from 9:00 a.m. to 7:30 p.m. Eastern time, Monday through Friday. Through LiveHelp, information specialists provide answers to questions about cancer and help in navigating Cancer.gov, the NCI’s Web site. Through the telephone numbers or LiveHelp service, CIS users receive: ·

Answers to their questions about cancer, including ways to prevent cancer, symptoms and risks, diagnosis, current treatments, and research studies;

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Written materials from the NCI;

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Referrals to clinical trials and cancer-related services, such as treatment centers, mammography facilities, or other cancer organizations;

·

Assistance in quitting smoking from information specialists trained in smoking cessation counseling. What Kind of Assistance Does the CIS Partnership Program Offer?

Through its Partnership Program, the CIS collaborates with established national, state, and regional organizations to reach minority and medically underserved audiences with cancer information. Partnership Program staff provide assistance to organizations developing programs that focus on breast and cervical cancer, clinical trials, tobacco control, and cancer awareness for special populations. To reach those in need, the CIS: ·

Helps bring cancer information to people who do not traditionally seek health information or who may have difficulties doing so because of educational, financial, cultural, or language barriers;

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Provides expertise to organizations to help strengthen their ability to inform people they serve about cancer; and

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Links organizations with similar goals and helps them plan and evaluate programs, develop coalitions, conduct training on cancer-related topics, and use NCI resources.

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How Do CIS Research Efforts Assist the Public? The CIS plays an important role in research by studying the most effective ways to communicate with people about healthy lifestyles; health risks; and options for preventing, diagnosing, and treating cancer. The ability to conduct health communications research is a unique aspect of the CIS. Results from these research studies can be applied to improving the way the CIS communicates about cancer and can help other programs communicate more effectively. How Do People Reach the Cancer Information Service? ·

To speak with a CIS information specialist call 1–800–4–CANCER (1–800– 422–6237), 9:00 a.m. to 4:30 p.m. local time, Monday through Friday. Deaf or hard of hearing callers with TTY equipment may call 1–800–332–8615.

·

To obtain online assistance visit the NCI’s Cancer Information Web site at http://cancer.gov/cancer_information and click on the LiveHelp link between 9:00 a.m. and 7:30 p.m. Eastern time, Monday through Friday.

·

For information 24 hours a day, 7 days a week call 1–800–4–CANCER and select option 4 to hear recorded information at any time.

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Visit NCI’s Web site at http://cancer.gov on the Internet.

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Visit the CIS Web site at http://cancer.gov/cis on the Internet.

Finding Cancer Resources in Your Community12 If you have cancer or are undergoing cancer treatment, there are places in your community to turn to for help. There are many local organizations throughout the country that offer a variety of practical and support services to people with cancer. However, people often don’t know about these services or are unable to find them. National cancer organizations can assist you in finding these resources, and there are a number of things you can do for yourself. Whether you are looking for a support group, counseling, advice, financial assistance, transportation to and from treatment, or information about cancer, most neighborhood organizations, local health care providers, or area hospitals are a good place to start. Often, the hardest part of looking for help is knowing the right questions to ask. 12

Adapted from the NCI: http://cis.nci.nih.gov/fact/8_9.htm.

Seeking Guidance 49

What Kind of Help Can I Get? Until now, you probably never thought about the many issues and difficulties that arise with a diagnosis of cancer. There are support services to help you deal with almost any type of problem that might occur. The first step in finding the help you need is knowing what types of services are available. The following pages describe some of these services and how to find them. ·

Information on Cancer. Most national cancer organizations provide a range of information services, including materials on different types of cancer, treatments, and treatment-related issues.

·

Counseling. While some people are reluctant to seek counseling, studies show that having someone to talk to reduces stress and helps people both mentally and physically. Counseling can also provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, self-help (sometimes called peer counseling), bereavement, patient-to-patient, and sexuality.

·

Medical Treatment Decisions. Often, people with cancer need to make complicated medical decisions. Many organizations provide hospital and physician referrals for second opinions and information on clinical trials (research studies with people), which may expand treatment options.

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Prevention and Early Detection. While cancer prevention may never be 100 percent effective, many things (such as quitting smoking and eating healthy foods) can greatly reduce a person’s risk for developing cancer. Prevention services usually focus on smoking cessation and nutrition. Early detection services, which are designed to detect cancer when a person has no symptoms of disease, can include referrals for screening mammograms, Pap tests, or prostate exams.

·

Home Health Care. Home health care assists patients who no longer need to stay in a hospital or nursing home, but still require professional medical help. Skilled nursing care, physical therapy, social work services, and nutrition counseling are all available at home.

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Hospice Care. Hospice is care focused on the special needs of terminally ill cancer patients. Sometimes called palliative care, it centers around providing comfort, controlling physical symptoms, and giving emotional support to patients who can no longer benefit from curative treatment. Hospice programs provide services in various settings, including the patient’s home, hospice centers, hospitals, or skilled nursing facilities. Your doctor or social worker can provide a referral for these services.

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·

Rehabilitation. Rehabilitation services help people adjust to the effects of cancer and its treatment. Physical rehabilitation focuses on recovery from the physical effects of surgery or the side effects associated with chemotherapy. Occupational or vocational therapy helps people readjust to everyday routines, get back to work, or find employment.

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Advocacy. Advocacy is a general term that refers to promoting or protecting the rights and interests of a certain group, such as cancer patients. Advocacy groups may offer services to assist with legal, ethical, medical, employment, legislative, or insurance issues, among others. For instance, if you feel your insurance company has not handled your claim fairly, you may want to advocate for a review of its decision.

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Financial. Having cancer can be a tremendous financial burden to cancer patients and their families. There are programs sponsored by the government and nonprofit organizations to help cancer patients with problems related to medical billing, insurance coverage, and reimbursement issues. There are also sources for financial assistance, and ways to get help collecting entitlements from Medicaid, Medicare, and the Social Security Administration.

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Housing/Lodging. Some organizations provide lodging for the family of a patient undergoing treatment, especially if it is a child who is ill and the parents are required to accompany the child to treatment.

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Children’s Services. A number of organizations provide services for children with cancer, including summer camps, make-a-wish programs, and help for parents seeking child care. How to Find These Services

Often, the services that people with cancer are looking for are right in their own neighborhood or city. The following is a list of places where you can begin your search for help. ·

The hospital, clinic, or medical center where you see your doctor, received your diagnosis, or where you undergo treatment should be able to give you information. Your doctor or nurse may be able to tell you about your specific medical condition, pain management, rehabilitation services, home nursing, or hospice care.

·

Most hospitals also have a social work, home care, or discharge planning department. This department may be able to help you find a support group, a nonprofit agency that helps people who have cancer, or the government agencies that oversee Social Security, Medicare, and

Seeking Guidance 51

Medicaid. While you are undergoing treatment, be sure to ask the hospital about transportation, practical assistance, or even temporary child care. Talk to a hospital financial counselor in the business office about developing a monthly payment plan if you need help with hospital expenses. ·

The public library is an excellent source of information, as are patient libraries at many cancer centers. A librarian can help you find books and articles through a literature search.

·

A local church, synagogue, YMCA or YWCA, or fraternal order may provide financial assistance, or may have volunteers who can help with transportation and home care. Catholic Charities, the United Way, or the American Red Cross may also operate local offices. Some of these organizations may provide home care, and the United Way’s information and referral service can refer you to an agency that provides financial help. To find the United Way serving your community, visit their online directory at http://www.unitedway.org on the Internet or look in the White Pages of your local telephone book.

·

Local or county government agencies may offer low-cost transportation (sometimes called para-transit) to individuals unable to use public transportation. Most states also have an Area Agency on Aging that offers low-cost services to people over 60. Your hospital or community social worker can direct you to government agencies for entitlements, including Social Security, state disability, Medicaid, income maintenance, and food stamps. (Keep in mind that most applications to entitlement programs take some time to process.) The Federal government also runs the Hill-Burton program (1–800–638–0742), which funds certain medical facilities and hospitals to provide cancer patients with free or low-cost care if they are in financial need. Getting the Most From a Service: What To Ask

No matter what type of help you are looking for, the only way to find resources to fit your needs is to ask the right questions. When you are calling an organization for information, it is important to think about what questions you are going to ask before you call. Many people find it helpful to write out their questions in advance, and to take notes during the call. Another good tip is to ask the name of the person with whom you are speaking in case you have follow-up questions. Below are some of the questions you may want to consider if you are calling or visiting a new agency and want to learn about how they can help:

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·

How do I apply [for this service]?

·

Are there eligibility requirements? What are they?

·

Is there an application process? How long will it take? What information will I need to complete the application process? Will I need anything else to get the service?

·

Do you have any other suggestions or ideas about where I can find help?

The most important thing to remember is that you will rarely receive help unless you ask for it. In fact, asking can be the hardest part of getting help. Don’t be afraid or ashamed to ask for assistance. Cancer is a very difficult disease, but there are people and services that can ease your burdens and help you focus on your treatment and recovery.

Finding Doctors Who Specialize in Cancer Care13 One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with melanoma must go through the process of selecting a physician. A common way to find a doctor who specializes in cancer care is to ask for a referral from your primary care physician. Sometimes, you may know a specialist yourself, or through the experience of a family member, coworker, or friend. The following resources may also be able to provide you with names of doctors who specialize in treating specific diseases or conditions. However, these resources may not have information about the quality of care that the doctors provide. ·

Your local hospital or its patient referral service may be able to provide you with a list of specialists who practice at that hospital.

·

Your nearest National Cancer Institute (NCI)-designated cancer center can provide information about doctors who practice at that center. The NCI fact sheet The National Cancer Institute Cancer Centers Program describes and gives contact information, including Web sites, for NCIdesignated cancer treatment centers around the country. Many of the cancer centers’ Web sites have searchable directories of physicians who practice at each facility. The NCI’s fact sheet is available at http://cis.nci.nih.gov/fact/1_2.htm on the Internet, or by calling the Cancer Information Service (CIS) at 1–800–4–CANCER (1–800–422–6237).

13

Adapted from the NCI: http://cis.nci.nih.gov/fact/7_47.htm.

Seeking Guidance 53

·

The American Board of Medical Specialties (ABMS) publishes a list of board-certified physicians. The Official ABMS Directory of Board Certified Medical Specialists lists doctors’ names along with their specialty and their educational background. This resource is available in most public libraries. The ABMS also has a Web site that can be used to verify whether a specific physician is board-certified. This free service is located at http://www.abms.org/newsearch.asp on the Internet. Verification of a physician’s board certification can also be obtained by calling the ABMS at 1–866–275–2267 (1–866–ASK–ABMS).

·

The American Medical Association (AMA) provides an online service called AMA Physician Select that offers basic professional information on virtually every licensed physician in the United States and its possessions. The database can be searched by doctor’s name or by medical specialty. The AMA Physician Select service is located at http://www.ama-assn.org/aps/amahg.htm on the Internet.

·

The American Society of Clinical Oncologists (ASCO) provides an online list of doctors who are members of ASCO. The member database has the names and affiliations of over 15,000 oncologists worldwide. It can be searched by doctor’s name, institution’s name, location, and/or type of board certification. This service is located at http://www.asco.org/people/db/html/m_db.htm on the Internet.

·

The American College of Surgeons (ACOS) Fellowship Database is an online list of surgeons who are Fellows of the ACOS. The list can be searched by doctor’s name, geographic location, or medical specialty. This service is located at http://web.facs.org/acsdir/default.htm on the Internet. The ACOS can be contacted at 633 North Saint Clair Street, Chicago, IL 60611–3211; or by telephone at 312–202–5000.

·

Local medical societies may maintain lists of doctors in each specialty.

·

Public and medical libraries may have print directories of doctors’ names, listed geographically by specialty.

·

Your local Yellow Pages may have doctors listed by specialty under “Physicians.”

The Agency for Healthcare Research and Quality (AHRQ) offers Your Guide to Choosing Quality Health Care, which has information for consumers on choosing a health plan, a doctor, a hospital, or a long-term care provider. The Guide includes suggestions and checklists that you can use to determine which doctor or hospital is best for you. This resource is available at http://www.ahrq.gov/consumer/qntool.htm on the Internet. You can also

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order the Guide by calling the AHRQ Publications Clearinghouse at 1–800– 358–9295. If you are a member of a health insurance plan, your choice may be limited to doctors who participate in your plan. Your insurance company can provide you with a list of participating primary care doctors and specialists. It is important to ask your insurance company if the doctor you choose is accepting new patients through your health plan. You also have the option of seeing a doctor outside your health plan and paying the costs yourself. If you have a choice of health insurance plans, you may first wish to consider which doctor or doctors you would like to use, then choose a plan that includes your chosen physician(s). The National Comprehensive Cancer Network (NCCN) Physician Directory lists specialists who practice in the NCCN’s 19 member institutions across the U.S. To access the directory, go to http://www.nccn.org/ and click on “Physician Directory“. To use this service, you will be required to scroll to the bottom of the page and select “I agree.” Enter your search criteria and select “Find” at the bottom of the page. To obtain more information on a physician or institution, contact the institution’s Physician Referral Department or the NCCN Patient Information and Referral Service at 1-888909-NCCN or [email protected]. If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

Selecting Your Doctor14 There are many factors to consider when choosing a doctor. To make the most informed decision, you may wish to speak with several doctors before choosing one. When you meet with each doctor, you might want to consider the following: ·

Does the doctor have the education and training to meet my needs?

·

Does the doctor use the hospital that I have chosen?

14 This

section has been adapted from the AHRQ: http://www.ahrq.gov/consumer/qntascii/qntdr.htm

Seeking Guidance 55

·

Does the doctor listen to me and treat me with respect?

·

Does the doctor explain things clearly and encourage me to ask questions?

·

What are the doctor’s office hours?

·

Who covers for the doctor when he or she is unavailable? Will that person have access to my medical records?

·

How long does it take to get an appointment with the doctor?

If you are choosing a surgeon, you may wish to ask additional questions about the surgeon’s background and experience with specific procedures. These questions may include: ·

Is the surgeon board-certified?15

·

Has the surgeon been evaluated by a national professional association of surgeons, such as the American College of Surgeons (ACOS)?

·

At which treatment facility or facilities does the surgeon practice?

·

How often does the surgeon perform the type of surgery I need?

·

How many of these procedures has the surgeon performed? What was the success rate?

It is important for you to feel comfortable with the specialist that you choose, because you will be working closely with that person to make decisions about your cancer treatment. Trust your own observations and feelings when deciding on a doctor for your medical care. Other health professionals and support services may also be important during cancer treatment. The National Cancer Institute fact sheet Your Health Care Team: Your Doctor Is Only the Beginning has information about these providers and services, and how to locate them. This fact sheet is located at http://cis.nci.nih.gov/fact/8_10.htm on the Internet, or can be obtained by calling the CIS at 1–800–4–CANCER (1–800–422–6237).

While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified.

15

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Working with Your Doctor16 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

·

It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

·

Bring a “health history” list with you (and keep it up to date).

·

Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

·

Tell your doctor about any natural or alternative medicines you are taking.

·

Bring other medical information, such as x-ray films, test results, and medical records.

·

Ask questions. If you don’t, your doctor will assume that you understood everything that was said.

·

Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

·

Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

·

Ask your doctor to draw pictures if you think that this would help you understand.

·

Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

·

Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

·

Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

16

Seeking Guidance 57

·

After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.

Finding a Cancer Treatment Facility17 Choosing a treatment facility is another important consideration for getting the best medical care possible. Although you may not be able to choose which hospital treats you in an emergency, you can choose a facility for scheduled and ongoing care. If you have already found a doctor for your cancer treatment, you may need to choose a facility based on where your doctor practices. Your doctor may be able to recommend a facility that provides quality care to meet your needs. You may wish to ask the following questions when considering a treatment facility: ·

Has the facility had experience and success in treating my condition?

·

Has the facility been rated by state, consumer, or other groups for its quality of care?

·

How does the facility check and work to improve its quality of care?

·

Has the facility been approved by a nationally recognized accrediting body, such as the American College of Surgeons (ACOS) and/or the Joint Commission on Accredited Healthcare Organizations (JCAHO)?

·

Does the facility explain patients’ rights and responsibilities? Are copies of this information available to patients?

·

Does the treatment facility offer support services, such as social workers and resources to help me find financial assistance if I need it?

·

Is the facility conveniently located?

If you are a member of a health insurance plan, your choice of treatment facilities may be limited to those that participate in your plan. Your Adapted from the NCI: http://cis.nci.nih.gov/fact/7_47.htm. At this Web site, information on how to find treatment facilities is also available for patients living outside the U.S.

17

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insurance company can provide you with a list of approved facilities. Although the costs of cancer treatment can be very high, you have the option of paying out-of-pocket if you want to use a treatment facility that is not covered by your insurance plan. If you are considering paying for treatment yourself, you may wish to discuss the potential costs with your doctor beforehand. You may also want to speak with the person who does the billing for the treatment facility. In some instances, nurses and social workers can provide you with more information about coverage, eligibility, and insurance issues. The following resources may help you find a hospital or treatment facility for your care: ·

The NCI fact sheet The National Cancer Institute Cancer Centers Program describes and gives contact information for NCI-designated cancer treatment centers around the country.

·

The ACOS accredits cancer programs at hospitals and other treatment facilities. More than 1,400 programs in the United States have been designated by the ACOS as Approved Cancer Programs. The ACOS Web site offers a searchable database of these programs at http://web.facs.org/cpm/default.htm on the Internet. The ACOS can be contacted at 633 North Saint Clair Street, Chicago, IL 60611–3211; or by telephone at 312–202–5000.

·

The JCAHO is an independent, not-for-profit organization that evaluates and accredits health care organizations and programs in the United States. It also offers information for the general public about choosing a treatment facility. The JCAHO Web site is located at http://www.jcaho.org on the Internet. The JCAHO is located at One Renaissance Boulevard, Oakbrook Terrace, IL 60181–4294. The telephone number is 630–792–5800.

·

The JCAHO offers an online Quality Check service that patients can use to determine whether a specific facility has been accredited by the JCAHO and view the organization’s performance reports. This service is located at http://www.jcaho.org/qualitycheck/directry/directry.asp on the Internet.

·

The AHRQ publication Your Guide To Choosing Quality Health Care has suggestions and checklists for choosing the treatment facility that is right for you.

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Additional Cancer Support Information In addition to the references above, the NCI has set up guidance Web sites that offers information on issues relating to cancer. These include: ·

Facing Forward - A Guide for Cancer Survivors: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=cc93a 843-6fc0-409e-8798-5c65afc172fe

·

Taking Time: Support for People With Cancer and the People Who Care About Them: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=21a4 6445-a5c8-4fee-95a3-d9d0d665077a

·

When Cancer Recurs: Meeting the Challenge: http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=9e13 d0d2-b7de-4bd6-87da-5750300a0dab

·

Your Health Care Team: Your Doctor Is Only the Beginning: http://cis.nci.nih.gov/fact/8_10.htm

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Bladder: The organ that stores urine. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Charities: Social welfare organizations with programs designed to assist individuals in times of need. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH]

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Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lymphoma: Cancer that arises in cells of the lymphatic system. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammogram: An x-ray of the breast. [NIH] Mammography: The use of x-rays to create a picture of the breast. [NIH] Melanosis: A disorder caused by a disturbance in melanin pigmentation; melanism. [EU] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Palliative: 1. affording relief, but not cure. 2. an alleviating medicine. [EU] Pancreatic: Having to do with the pancreas. [NIH] Pap test: The collection of cells from the cervix for examination under a microscope. It is used to detect changes that may be cancer or may lead to cancer, and can show noncancerous conditions, such as infection or inflammation. Also called a Pap smear. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Stomach: An organ that is part of the digestive system. It helps in the digestion of food by mixing it with digestive juices and churning it into a thin liquid. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH]

Clinical Trials 61

CHAPTER 3. CLINICAL TRIALS AND MELANOMA Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning melanoma.

What Is a Clinical Trial?18 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for melanoma is to try it on patients in a clinical trial.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

18

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What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on melanoma.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for melanoma compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?

Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on melanoma carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on melanoma. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This

Clinical Trials 63

treatment, like a placebo, has no effect on melanoma and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how melanoma develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for melanoma. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial’s investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo

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surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Melanoma The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to melanoma.19 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

Antineoplaston Therapy in Treating Patients With Stage IV Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: Rationale: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. Purpose: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with progressive or recurrent stage IV melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): Texas; Burzynski Research Institute, Houston, Texas, 77055, United States; Recruiting; Stanislaw R. Burzynski 713-335-5697. Study chairs or principal investigators: Stanislaw R. Burzynski, Study Chair; Burzynski Research Institute

19

These are listed at www.ClinicalTrials.gov.

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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003509;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

BCG With or Without Melanoma Vaccine in Treating Patients After Surgery to Remove Stage IV Melanoma Condition(s): stage IV melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); John Wayne Cancer Institute Purpose - Excerpt: Rationale: Vaccines may make the body build an immune response that will kill tumor cells. It is not yet known whether BCG plus melanoma vaccine is more effective than BCG alone after surgery to remove stage IV melanoma. Purpose: Randomized phase III trial to compare the effectiveness of BCG with or without melanoma vaccine in treating patients who have undergone surgery to remove stage IV melanoma. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003722;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

·

BCG With or Without Vaccine Therapy in Treating Patients With Stage III Melanoma That Has Been Surgically Removed Condition(s): stage III melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): John Wayne Cancer Institute Purpose - Excerpt: Rationale: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known if BCG plus vaccine therapy is more effective than BCG alone in treating patients who have melanoma that has been surgically removed. Purpose: Randomized double-blinded phase III trial to study the effectiveness of BCG with or without melanoma vaccine in treating patients who have stage III melanoma that has been surgically removed. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004130;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Bevacizumab With or Without Interferon alfa in Treating Patients With Metastatic Malignant Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Arthur G. James Cancer Hospital & Richard J. Solove Research Institute Purpose - Excerpt: Rationale: Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumorkilling substances to them without harming normal cells. Interferon alfa may interfere with the growth of the cancer cells and slow the growth of the tumor. Combining bevacizumab with interferon alfa may kill more tumor cells. Purpose: Randomized phase II trial to compare the effectiveness of bevacizumab with or without interferon alfa in treating patients who have metastatic malignant melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): Ohio; Arthur G. James Cancer Hospital - Ohio State University, Columbus, Ohio, 43210-1240, United States; Recruiting; William Edgar Carson, III 614-292-5819; Cincinnati HematologyOncology, Inc., Cincinnati, Ohio, 45209, United States; Recruiting; Philip D. Leming 513-585-1777. Study chairs or principal investigators: William Edgar Carson, III, Study Chair; Arthur G. James Cancer Hospital & Richard J. Solove Research Institute Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00026221;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

·

Biological Therapy and Temozolomide in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): St. Luke's Medical Center Purpose - Excerpt: Rationale: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Drugs used in chemotherapy use different ways to stop tumor cells from

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dividing so they stop growing or die. Combining biological therapy with chemotherapy may kill more tumor cells. Purpose: Phase I trial to study the effectiveness of biological therapy combined with temozolomide in treating patients who have metastatic melanoma. Phase(s): Phase I Study Type: Treatment Contact(s): Wisconsin; St. Luke's Medical Center, Milwaukee, Wisconsin, 53215, United States; Recruiting; John P. Hanson, Jr. 414-385-3086. Study chairs or principal investigators: John P. Hanson, Jr., Study Chair; St. Luke's Medical Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00016055;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Biological Therapy in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: Rationale: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Purpose: Phase I/II trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): Washington; Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109-1024, United States; Recruiting; Cassian Yee 206-667-6287. Study chairs or principal investigators: Cassian Yee, Study Chair; Fred Hutchinson Cancer Research Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002786;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Chemotherapy Followed by Biological Therapy in Treating Patients With Stage IV Melanoma That Cannot be Treated With Surgery Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): St. Francis Hospital

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Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies such as interleukin-2 and interferon alfa stimulate a person's white blood cells to kill cancer cells or may interfere with the growth of cancer cells. Combining chemotherapy with biological therapies may kill more tumor cells. Purpose: Phase II trial to study the effectiveness of temozolomide followed by sargramostim, interleukin-2, and interferon alfa in treating patients who have stage IV melanoma that cannot be treated with surgery. Phase(s): Phase II Study Type: Treatment Contact(s): California; John Wayne Cancer Institute, Santa Monica, California, 90404, United States; Recruiting; Steven O'Day 310-998-3961; St. Francis Hospital, San Francisco, California, 94109, United States; Recruiting; Lynn E. Spitler 415-435-9861; Colorado; University of Colorado Cancer Center, Denver, Colorado, 80010, United States; Recruiting; Rene Gonzalez 720-848-0581. Study chairs or principal investigators: Lynn E. Spitler, Study Chair; St. Francis Hospital Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00014092;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma Condition(s): stage III melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group; Cancer and Leukemia Group B; Southwest Oncology Group Purpose - Excerpt: Rationale: Interferon alfa may interfere with the growth of cancer cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa is more effective with or without combination chemotherapy and interleukin-2 for melanoma. Purpose: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy consisting of cisplatin, vinblastine, and dacarbazine, plus interleukin-2 in treating patients who have melanoma. Phase(s): Phase III

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Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006237;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Melanoma or Metastatic Kidney Cancer Condition(s): stage IV melanoma; stage IV renal cell cancer; recurrent renal cell cancer; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Chicago Cancer Research Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. Purpose: Phase II trial to study the effectiveness of chemotherapy plus peripheral stem cell transplantation in treating patients who have metastatic kidney cancer or melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): Illinois; University of Chicago Cancer Research Center, Chicago, Illinois, 60637-1470, United States; Recruiting; Todd M. Zimmerman 773-702-4159. Study chairs or principal investigators: Todd M. Zimmerman, Study Chair; University of Chicago Cancer Research Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004135;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Combination Chemotherapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage III melanoma; stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center

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Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Purpose: Phase I/II trial to study the effectiveness of combination chemotherapy consisting of acetaminophen plus carmustine in treating patients who have stage III or stage IV melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Paul B. Chapman 212639-5015. Study chairs or principal investigators: Paul B. Chapman, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003346;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Combination Chemotherapy Plus Biological Therapy in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma; stage III melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Chicago Cancer Research Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies use different ways to stimulate the immune system and stop cancer cell from growing. Combining more than one drug with different types of biological therapies may kill more tumor cells. Purpose: Phase II trial to study the effectiveness of combination chemotherapy plus biological therapy in treating patients who have metastatic melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): Illinois; University of Chicago Cancer Research Center, Chicago, Illinois, 60637-1470, United States; Recruiting; Thomas F. Gajewski 773-702-4601. Study chairs or principal investigators: Thomas F. Gajewski, Study Chair; University of Chicago Cancer Research Center

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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004141;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Combination Chemotherapy With or Without Interleukin-2 and Interferon alfa in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Southwest Oncology Group; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. Interferon alfa may interfere with the growth of tumor cells. It is not yet known whether combination chemotherapy plus interleukin-2 and interferon alfa is more effective than combination chemotherapy alone for metastatic melanoma. Purpose: Randomized phase III trial to compare combination chemotherapy with or without interleukin-2 and interferon alfa in treating patients who have metastatic melanoma that cannot be treated by surgery. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003027;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Combination Chemotherapy, Interferon alfa, and Interleukin-2 in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of the cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known which treatment regimen is more effective in treating melanoma. Purpose: Randomized phase II trial to compare the effectiveness of two regimens of combination chemotherapy plus

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interferon alfa and interleukin-2 in treating patients who have metastatic melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002669;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Combination Chemotherapy, Total-Body Irradiation, Peripheral Stem Cell Transplantation, and Lymphocyte Infusion in Treating Patients With Stage IV Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells can reject the body's normal tissues. Donor lymphocytes that have been treated in the laboratory may prevent this. Purpose: Phase II trial to study the effectiveness of combination chemotherapy, total-body irradiation, peripheral stem cell transplantation, and lymphocyte infusion in treating patients who have stage IV melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): Washington; Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109-1024, United States; Recruiting; John A. Thompson 206-288-2041. Study chairs or principal investigators: John A. Thompson, Study Chair; Fred Hutchinson Cancer Research Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006233;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Dacarbazine With or Without Bcl-2 Antisense Oligodeoxynucleotide G3139 in Treating Patients With Advanced Malignant Melanoma Condition(s): stage IV melanoma; stage III melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Genta Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bcl-2 antisense oligodeoxynucleotide G3139 may help dacarbazine kill more cancer cells by making tumor cells more sensitive to the drug. It is not yet known if dacarbazine is more effective with or without bcl-2 antisense oligodeoxynucleotide G3139. Purpose: Randomized phase III trial to compare the effectiveness of dacarbazine with or without bcl-2 antisense oligodeoxynucleotide G3139 in treating patients who have advanced malignant melanoma. Phase(s): Phase III Study Type: Treatment Contact(s): New Jersey; Genta Incorporated, Berkeley Heights, New Jersey, 07922, United States; Recruiting; Patient Inquiries Genta Incorporated 908-286-9800. Study chairs or principal investigators: Stanley R. Frankel, Study Chair; Genta Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00016263;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Detection of Melanoma Markers in Lymph Nodes or Peripheral Blood of Patients With Melanoma Condition(s): stage IV melanoma; stage I melanoma; stage II melanoma; stage III melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Chicago Cancer Research Center Purpose - Excerpt: Rationale: Diagnostic procedures may improve the ability to detect the presence or recurrence of disease. Purpose: Diagnostic trial to detect melanoma markers in the lymph nodes or peripheral blood of patients who have melanoma. Study Type: Diagnostic Contact(s): Illinois; University of Chicago Cancer Research Center, Chicago, Illinois, 60637-1470, United States; Recruiting; Mitchell C.

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Posner 773-834-0156. Study chairs or principal investigators: Thomas F. Gajewski, Study Chair; University of Chicago Cancer Research Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004153;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Flavopiridol in Treating Patients With Metastatic Malignant Melanoma Condition(s): stage IV melanoma Study Status: This study is currently recruiting patients. Sponsor(s): NCIC-Clinical Trials Group Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Purpose: Phase II trial to study the effectiveness of flavopiridol in treating patients who have metastatic malignant melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005971;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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High-Dose Interferon alfa in Treating Patients With Stage II or Stage III Melanoma Condition(s): stage II melanoma; stage III melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group Purpose - Excerpt: Rationale: Interferon alfa may interfere with the growth of cancer cells. It is not yet known whether treatment with interferon alfa is more effective than observation alone for stage II or stage III melanoma that has been completely removed surgically. Purpose: Randomized phase III trial to determine the effectiveness of high-dose interferon alfa in treating patients who have stage II or stage III melanoma that has been completely removed surgically. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003641;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Immunotherapy After Surgery in Treating Patients With Breast Cancer, Colon Cancer, or Melanoma Condition(s): stage II melanoma; recurrent colon cancer; stage II breast cancer; stage I colon cancer; recurrent melanoma; stage III colon cancer; stage I melanoma; recurrent breast cancer; stage III melanoma; stage I breast cancer; stage IIIA breast cancer; stage II colon cancer Study Status: This study is currently recruiting patients. Sponsor(s): Centro Oncologico de Excelencia Purpose - Excerpt: Rationale: Immunotherapy uses different ways to stimulate the immune system and stop cancer cells from growing. Immunotherapy biological extracts may be useful as adjuvant therapy in treating patients who have had surgery for breast cancer, colon cancer, or melanoma. Purpose: Phase III trial to study the effectiveness of Corynebacterium granulosum extract as maintenance immunotherapy following surgery in treating patients with breast cancer, colon cancer, or melanoma. Phase(s): Phase III Study Type: Treatment Contact(s): Argentina, Buenos Aires; Centro Oncologico de Excelencia, Gonnet, Buenos Aires, 1987 MB, Argentina; Recruiting; Hugo Omar De Carli 021-84-3119. Study chairs or principal investigators: Hugo Omar De Carli, Study Chair; Centro Oncologico de Excelencia Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002455;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Interferon alfa Following Surgery in Treating Patients With Stage III Melanoma Condition(s): stage III melanoma Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: Rationale: Interferon alfa may interfere with the growth of the cancer cells. It is not yet known if this treatment is more effective than observation following surgery for stage III melanoma. Purpose: Randomized phase III trial to determine the effectiveness of

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interferon alfa in treating patients who have undergone surgery for stage III melanoma. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006249;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Interferon alfa With or Without Combination Chemotherapy Plus Interleukin-2 in Treating Patients With Melanoma Condition(s): stage III melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); M.D. Anderson Cancer Center Purpose - Excerpt: Rationale: Interferon alfa may interfere with the growth of cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa plus combination chemotherapy and interleukin-2 is more effective than interferon alfa alone in treating patients with melanoma. Purpose: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy plus interleukin-2 in treating patients with melanoma. Phase(s): Phase III Study Type: Treatment Contact(s): Texas; University of Texas - MD Anderson Cancer Center, Houston, Texas, 77030-4009, United States; Recruiting; Agop Y. Bedikian 713-792-2921. Study chairs or principal investigators: Agop Y. Bedikian, Study Chair; M.D. Anderson Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002882;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Interferon alfa-2b in Treating Patients With Melanoma and Early Lymph Node Metastasis Condition(s): stage I melanoma; stage II melanoma; stage III melanoma Study Status: This study is currently recruiting patients.

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Sponsor(s): National Cancer Institute (NCI); UAB Comprehensive Cancer Center Purpose - Excerpt: Rationale: Interferon alfa-2b may interfere with the growth of cancer cells. Purpose: Randomized phase III trial to study the effectiveness of interferon alfa-2b in treating patients who have melanoma with early lymph node metastasis. Phase(s): Phase III Study Type: Treatment, Diagnostic Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004196;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Interleukin-12 and Interferon alfa in Treating Patients With Metastatic Kidney Cancer or Malignant Melanoma Condition(s): stage IV melanoma; stage IV renal cell cancer; recurrent renal cell cancer; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Cleveland Clinic Cancer Center Purpose - Excerpt: Rationale: Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Interferon alfa may interfere with the growth of cancer cells. Combining interleukin-12 and interferon alfa may kill more cancer cells. Purpose: Phase I trial to study the effectiveness of interleukin-12 and interferon alfa in treating patients who have metastatic kidney cancer or malignant melanoma. Phase(s): Phase I Study Type: Treatment Contact(s): Ohio; Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio, 44195, United States; Recruiting; Ronald M. Bukowski 216-4446825. Study chairs or principal investigators: Ronald M. Bukowski, Study Chair; Cleveland Clinic Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004244;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Interleukin-2 Plus Bryostatin 1 in Treating Patients With Melanoma or Kidney Cancer Condition(s): stage IV melanoma; stage III renal cell cancer; stage IV renal cell cancer; stage III melanoma; recurrent renal cell cancer; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Massey Cancer Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining bryostatin 1 with interleukin-2 may kill more tumor cells. Purpose: Randomized phase I trial to study the effectiveness of interleukin-2 plus bryostatin 1 in treating patients who have melanoma or kidney cancer that cannot be removed during surgery. Phase(s): Phase I Study Type: Treatment Contact(s): New Hampshire; Norris Cotton Cancer Center, Lebanon, New Hampshire, 03756-0002, United States; Recruiting; Marc Stuart Ernstoff 603-650-5534; Virginia; Massey Cancer Center, Richmond, Virginia, 23298-0037, United States; Recruiting; John D. Roberts 804-6281940. Study chairs or principal investigators: John D. Roberts, Study Chair; Massey Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006022;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Interleukin-2 With or Without Histamine Dihydrochloride in Treating Patients With Stage IV Melanoma Metastatic to the Liver Condition(s): stage IV melanoma; liver metastases; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Maxim Pharmaceuticals Purpose - Excerpt: Rationale: Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Histamine dihydrochloride may help interleukin-2 kill more tumor cells by making tumor cells more sensitive to the drug. It is not yet known if interleukin-2 is more effective with or without histamine dihydrochloride in treating stage IV melanoma that is metastatic to the liver. Purpose: Randomized phase III trial to compare the effectiveness of interleukin-2 with or without histamine

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dihydrochloride in treating patients who have stage IV melanoma that is metastatic to the liver. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00039234;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Isolated Limb Infusion of Chemotherapy in Treating Patients With Melanoma or Soft Tissue Sarcoma of the Arm or Leg That Cannot Be Removed By Surgery Condition(s): stage IVB adult soft tissue sarcoma; stage IV melanoma; recurrent adult soft tissue sarcoma; stage III melanoma; recurrent melanoma; stage IVA adult soft tissue sarcoma; stage III adult soft tissue sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Infusing chemotherapy to the tumor area only may kill more tumor cells and cause less damage to healthy tissues. Purpose: Phase II trial to study the effectiveness of isolated limb infusion of chemotherapy in treating patients who have melanoma or soft tissue sarcoma of the arm or leg that cannot be removed by surgery. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Mary Susan Brady 212639-8347. Study chairs or principal investigators: Mary Susan Brady, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004250;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Melanoma Vaccine With or Without Sargramostim in Treating Patients With Stage IV Malignant Melanoma Condition(s): stage IV melanoma; recurrent melanoma

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Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Mayo Clinic Cancer Center Purpose - Excerpt: Rationale: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Purpose: Randomized phase I trial to compare the effectiveness of melanoma vaccine with or without sargramostim in treating patients who have stage IV malignant melanoma. Phase(s): Phase I Study Type: Treatment Contact(s): Arizona; Mayo Clinic Scottsdale, Scottsdale, Arizona, 85259, United States; Recruiting; Michael K. Gornet 480-301-8000; Florida; Mayo Clinic, Jacksonville, Florida, 32224, United States; Recruiting; William J. Maples 904-953-7292; Minnesota; Mayo Clinic Cancer Center, Rochester, Minnesota, 55905, United States; Recruiting; Svetomir Markovic 507-2843903. Study chairs or principal investigators: Svetomir Markovic, Study Chair; Mayo Clinic Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006243;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Melphalan With or Without Tumor Necrosis Factor in Treating Patients With Advanced Melanoma of the Arm or Leg Condition(s): stage III melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); American College of Surgeons Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Heating melphalan to several degrees above body temperature and infusing it only to the area around the tumor may kill more tumor cells. It is not yet known whether melphalan plus tumor necrosis factor is more effective than melphalan alone in treating melanoma. Purpose: Randomized phase III trial to compare the effectiveness of a hyperthermic perfusion of melphalan with or without tumor necrosis factor in treating patients who have advanced melanoma of the arm or leg. Phase(s): Phase III

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Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003789;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

O6-benzylguanine and Carmustine in Treating Patients Unresectable Locally Recurrent or Metastatic Melanoma

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Condition(s): stage IV melanoma; stage III melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Chicago Cancer Research Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than once chemotherapy drug may kill more tumor cells. Purpose: Phase II trial to study the effectiveness of O6benzylguanine and carmustine in treating patients who have unresectable locally recurrent or metastatic melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005961;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Peripheral Stem Cell Transplantation Plus Monoclonal Antibody Therapy in Treating Patients With High-Risk Hematologic Cancer, Refractory Breast or Kidney Cancer, or Melanoma Condition(s): leukemia; renal cell cancer; melanoma; breast cancer; kidney tumor Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Duke Comprehensive Cancer Center Purpose - Excerpt: Rationale: Peripheral stem cell transplantation replaces immune cells that were destroyed by chemotherapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment of the cells with a

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monoclonal antibody may prevent this from happening. Purpose: Phase II trial to study the effectiveness of peripheral stem cell transplantation plus monoclonal antibody therapy in treating patients who have highrisk hematologic cancer, refractory breast or kidney cancer, or melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): North Carolina; Duke Comprehensive Cancer Center, Durham, North Carolina, 27710, United States; Recruiting; David A. Rizzieri 919-668-1040. Study chairs or principal investigators: David A. Rizzieri, Study Chair; Duke Comprehensive Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004143;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Phase I Study of gp75 Vaccine in Patients with Stage III and IV Melanoma Condition(s): Malignant Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): ImClone Systems; MSKCC Memorial Hospital, New York, NY Purpose - Excerpt: Up to 24 patients with stage III or stage IV melanoma who are currently disease-free but at high risk for relapse will be enrolled. Patients will receive vaccinations of gp75 at assigned dose levels. Patients who exhibit serologic and stable/clinical response are elible to receive booster vaccinations. Patients will be evaluated for safety and efficacy throughout the duration of the study. In this study, the optimal biologically effective dose is defined as the lowest dose of gp75 that results in the production of anti-gp75 antibodies. Phase(s): Phase I Study Type: Interventional Contact(s): New York; MSKCC Memorial Hospital, New York, New York, 10021, United States; Recruiting; Jedd Wolchok, MD 212-639-6570; Jedd Wolchok, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00034554;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Pyrazoloacridine in Treating Patients With Metastatic Skin or Eye Melanoma Condition(s): ciliary body and choroid melanoma, medium/large size; stage IV melanoma; extraocular extension melanoma; recurrent intraocular melanoma; iris melanoma; recurrent melanoma; ciliary body and choroid melanoma, small size Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Sidney Kimmel Cancer Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Purpose: Phase II trial to study the effectiveness of pyrazoloacridine in treating patients who have metastatic skin or eye melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): Maryland; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, 21231-2410, United States; Recruiting; William Howard Sharfman 410-583-2970. Study chairs or principal investigators: William Howard Sharfman, Study Chair; Sidney Kimmel Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003802;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Radiation Therapy in Treating Patients With Newly Diagnosed Brain Metastases From Kidney Cancer, Melanoma, or Sarcoma Condition(s): brain metastases; stage IVB adult soft tissue sarcoma; stage IV uterine sarcoma; stage IV melanoma; metastatic tumors of the Ewing's family; stage IV renal cell cancer; chondrosarcoma; metastatic osteosarcoma; ovarian sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group Purpose - Excerpt: Rationale: Radiation therapy uses high-energy x-rays to damage tumor cells. Purpose: Phase II trial to study the effectiveness of radiation therapy in treating patients with newly diagnosed brain metastases from kidney cancer, melanoma, or sarcoma. Phase(s): Phase II Study Type: Treatment

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003308;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

SU5416 in Treating Patients With Metastatic Melanoma That Has Been Previously Treated Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Chicago Cancer Research Center Purpose - Excerpt: Rationale: SU5416 may stop the growth of malignant melanoma by stopping blood flow to the tumor. Purpose: Phase II trial to study the effectiveness of SU5416 in treating patients who have metastatic melanoma that has been previously treated. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006003;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Surgery in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group; Southwest Oncology Group Purpose - Excerpt: Rationale: Surgery may be effective therapy in treating patients with metastatic melanoma. Purpose: Phase II trial to study the effectiveness of surgery in treating patients with metastatic melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00002860;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Temozolomide and Interferon alfa in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage IV melanoma; extraocular extension melanoma; recurrent intraocular melanoma; stage III melanoma; iris melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of cancer cells. Combining chemotherapy with interferon alfa may kill more tumor cells. Purpose: Phase II trial to study the effectiveness of combining temozolomide and interferon alfa in treating patients who have stage III or stage IV melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Wen-Jen Hwu 212-6395096. Study chairs or principal investigators: Wen-Jen Hwu, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00027742;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Temozolomide and Thalidomide in Treating Patients With Stage III or Stage IV Melanoma Condition(s): ciliary body and choroid melanoma, medium/large size; stage IV melanoma; extraocular extension melanoma; recurrent intraocular melanoma; stage III melanoma; iris melanoma; recurrent melanoma; ciliary body and choroid melanoma, small size Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: Rationale: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of melanoma by stopping blood flow to the tumor. Combining chemotherapy with thalidomide may kill more tumor cells. Purpose: Phase I/II trial to study the effectiveness

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temozolomide plus thalidomide in treating patients who have stage III or stage IV melanoma that cannot be removed during surgery. Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): New York; Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting; Paul B. Chapman 212639-5015. Study chairs or principal investigators: Wen-Jen Hwu, Study Chair; Memorial Sloan-Kettering Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005815;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Vaccine Plus Interleukin-2 in Treating Patients With Advanced Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Cancer and Leukemia Group B Purpose - Excerpt: Rationale: Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Melanoma vaccine plus interleukin-2 may kill more cancer cells. Purpose: Phase II trial to study the effectiveness of vaccine therapy plus interleukin-2 in treating patients who have advanced melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005949;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Vaccine Therapy and Interleukin-12 With Either Alum Sargramostim After Surgery in Treating Patients With Melanoma

or

Condition(s): ciliary body and choroid melanoma, medium/large size; stage IV melanoma; extraocular extension melanoma; recurrent intraocular melanoma; stage II melanoma; stage III melanoma; iris melanoma; recurrent melanoma; ciliary body and choroid melanoma, small size

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Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Southern California Purpose - Excerpt: Rationale: Vaccines made from peptides may make the body build an immune response. Combining vaccine therapy with interleukin-12 and either alum or sargramostim may kill more tumor cells. Purpose: Randomized phase II trial to compare the effectiveness of combining vaccine therapy with interleukin-12 and either alum or sargramostim in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): California; USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles, California, 90033-0804, United States; Recruiting; Jeffrey S. Weber 323-865-0712. Study chairs or principal investigators: Jeffrey S. Weber, Study Chair; University of Southern California Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00031733;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Vaccine Therapy and/or Sargramostim in Treating Patients With Locally or Advanced Metastatic Melanoma Condition(s): ciliary body and choroid melanoma, medium/large size; stage IV melanoma; extraocular extension melanoma; recurrent intraocular melanoma; stage III melanoma; iris melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group Purpose - Excerpt: Rationale: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. It is not yet known which treatment regimen is more effective for metastatic melanoma. Purpose: Randomized phase III trial to determine the effectiveness of peptide vaccine therapy and/or sargramostim in treating patients who have locally advanced or metastatic melanoma. Phase(s): Phase III Study Type: Treatment

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005034;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Vaccine Therapy Followed by Biological Therapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage IV melanoma; stage III melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Southern California Purpose - Excerpt: Rationale: Vaccines made from melanoma cells may make the body build an immune response to kill tumor cells. Biological therapies such as interferon gamma and interleukin-2 use different ways to stimulate the immune system and stop cancer cells from growing. Combining vaccine therapy with biological therapy may kill more tumor cells. Purpose: Phase II trial to study the effectiveness of vaccine therapy, interferon gamma, and interleukin-2 in treating patients who have stage III or stage IV melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): California; USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles, California, 90033-0804, United States; Recruiting; Jeffrey S. Weber 323-865-0712. Study chairs or principal investigators: Jeffrey S. Weber, Study Chair; University of Southern California Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006113;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Vaccine Therapy in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Baylor University Purpose - Excerpt: Rationale: Vaccines made from a patient's white blood cells mixed with tumor antigens may make the body build an immune response to kill tumor cells. Purpose: Phase I trial to study the effectiveness of vaccine therapy in treating patients who have metastatic melanoma.

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Phase(s): Phase I Study Type: Treatment Contact(s): Texas; Baylor University Medical Center, Dallas, Texas, 75246, United States; Recruiting; Joseph Wayne Fay 214-370-1500. Study chairs or principal investigators: Joseph Wayne Fay, Study Chair; Baylor University Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00017355;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Vaccine Therapy in Treating Patients With Primary Stage II Melanoma Condition(s): stage II melanoma Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: Rationale: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether vaccine therapy is more effective than observation alone for melanoma. Purpose: Randomized phase III trial to determine the effectiveness of vaccine therapy in treating patients who have primary stage II melanoma. Phase(s): Phase III Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005052;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Vaccine Therapy in Treating Patients With Stage IV or Recurrent Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Hoag Memorial Hospital Presbyterian Purpose - Excerpt: Rationale: Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells. Purpose: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV or recurrent melanoma. Phase(s): Phase I; Phase II Study Type: Treatment

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Contact(s): California; Hoag Memorial Hospital Presbyterian, Newport Beach, California, 92658, United States; Recruiting; Robert O. Dillman 949-760-2091. Study chairs or principal investigators: Robert O. Dillman, Study Chair; Hoag Memorial Hospital Presbyterian Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00012064;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Vaccine Therapy in Treating Patients With Stage IV or Relapsed Malignant Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Jonsson Comprehensive Cancer Center Purpose - Excerpt: Rationale: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Purpose: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV, or relapsed malignant melanoma . Phase(s): Phase I; Phase II Study Type: Treatment Contact(s): California; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, 90095-1781, United States; Recruiting; John A. Glaspy 310-794-1274. Study chairs or principal investigators: James S. Economou, Study Chair; Jonsson Comprehensive Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005617;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Vaccine Therapy With High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Illinois Purpose - Excerpt: Rationale: Vaccines may make the body build an immune response that will kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. Purpose: Randomized phase II trial to study the effectiveness of vaccine therapy with interleukin-2 in treating patients with metastatic melanoma.

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Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00003568;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Vaccine Therapy With or Without Biological Therapy in Treating Patients With Metastatic Melanoma Condition(s): stage IV melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group Purpose - Excerpt: Rationale: Vaccines may make the body build an immune response to kill tumor cells. Biological therapies such as sargramostim and interferon alfa use different ways to stimulate the immune system and stop cancer cells from growing. It is not yet known if vaccine therapy if more effective with or without biological therapy for melanoma. Purpose: Randomized phase II trial to compare the effectiveness of vaccine therapy with or without biological therapy in treating patients who have metastatic melanoma. Phase(s): Phase II Study Type: Treatment Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006385;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Vaccine Therapy With or Without Sargramostim in Treating Patients With High-Risk or Metastatic Melanoma Condition(s): stage IV melanoma; stage III melanoma; recurrent melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Comprehensive Cancer Center

Institute

(NCI);

Herbert

Irving

Purpose - Excerpt: Rationale: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells

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found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may kill more tumor cells. Purpose: Randomized phase I trial to study the effectiveness of vaccine therapy with or without sargramostim in treating patients who have metastatic melanoma. Phase(s): Phase I Study Type: Treatment Contact(s): New York; Herbert Irving Comprehensive Cancer Center, New York, New York, 10032, United States; Recruiting; Kyriakos P. Papadopoulos 212-305-8615. Study chairs or principal investigators: Kyriakos P. Papadopoulos, Study Chair; Herbert Irving Comprehensive Cancer Center Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00037037;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9 ·

Phase I Trial in Patients with Metastatic Melanoma of Immunization with a Recombinant Fowlpox Virus Encoding the gp100 Melanoma Antigen Condition(s): Melanoma; Neoplasm Metastasis Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Vaccination with and without Biological Response Modifier Therapy. Vaccination with recombinant fowlpox virus encoding the gp100 melanoma antigen, FPV-gp100, NSC-673927; with and without Interleukin-2 (Chiron), IL-2, NSC-373364. Phase(s): Phase I Study Type: Interventional Contact(s): Maryland; National Cancer Institute (NCI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001510;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

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Flt3L and CD40L to Treat Metastatic Melanoma and Kidney Cancer Condition(s): Melanoma; Renal Cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI)

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Purpose - Excerpt: The purpose of this study is to find the largest dose of CD40 L that can be given safely with Flt3L in patients with kidney cancer or metastatic melanoma (melanoma that has spread beyond the original site). Each drug alone has been used safely, but the two have not been used in combination before this study. Flt3L increases the number of a type of immune cell called dendritic cells, which are known to enhance the immune response. CD40L works to activate the response of these cells. Patients 16 years of age and older with metastatic melanoma or kidney cancer that cannot be cured with conventional treatments such as surgery, radiation therapy and chemotherapy may be eligible for this study. Candidates will be screened with a physical examination, blood and urine tests, chest X-ray, electrocardiogram, and X-rays and scans to evaluate disease status. Participants will have an injection of Flt3L under the skin every day for 14 days. (Patients or a caregiver will be taught how to administer the injections.) On the 12th day of treatment, patients will also begin receiving CD40L under the skin, for 5 days. If the patients starting at this lowest dose of CD40L do not experience any significant side effects, the dose will be increased for the next group of patients. The dose will be increased a third time if patients in the second group do not have significant side effects. The treatment cycle may be repeated after 28 days from the start of the injections. Patients will undergo leukapheresis to collect white blood cells before beginning treatment and again around day 17. For this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are then removed, and the red cells, platelets and plasma are returned to the body through a second needle placed in the other arm. Patients will be evaluated with a physical examination, X-rays and scans after two cycles for the response to treatment. Patients whose tumors shrink and patients with a mixed response (i.e., some tumors shrink and others enlarge) may be offered up to a total of 6 treatment cycles. Patients whose disease remains stable or worsens will stop Flt3L and CD40 and may be offered treatment with interleukin-2, a substance that may boost the body's immune response to the tumor. Patients will have frequent blood tests. Some patients may have a skin biopsy to evaluate the effects of Flt3L and CD40L. For the biopsy, a small area of skin is numbed with an anesthetic and less than one-quarter inch of skin is removed for study under the microscope. Phase(s): Phase I Study Type: Interventional Contact(s): Maryland; National Cancer Institute (NCI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States

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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00012532;jsessionid=06656C2 9B893FD5E8F08C123BA6D59E9

Benefits and Risks20 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for melanoma. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

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If the treatment is effective, then it may improve health or prevent diseases or disorders.

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Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

·

People who take part in trials contribute to scientific discoveries that may help other people with melanoma. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you, and your rights as a patient.

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f291.

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What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention.

How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent.

What Are a Patient’s Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

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Know how the researchers plan to carry out the study, for how long, and where.

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Know what is expected of you.

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Know any costs involved for you or your insurance provider.

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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

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Talk openly with doctors and ask any questions.

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After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

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Receive any new information about the new treatment.

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Continue to ask questions and get answers.

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Maintain your privacy. Your name will not appear in any reports based on the study.

·

Know whether you participated in the treatment group or the control group (once the study has been completed). What Should You Ask before Deciding to Join a Clinical Trial?

Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

·

What are the standard treatments for melanoma? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

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What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

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How long will the treatment last? How often will I have to come back for follow-up exams?

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What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

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Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

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How will my health be monitored?

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Where will I need to go for the clinical trial? How will I get there?

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How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

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Will I be able to see my own doctor? Who will be in charge of my care?

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Will taking part in the study affect my daily life? Do I have time to participate?

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·

How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Clinical Trials and Insurance Coverage21 As you consider enrolling in a clinical trial, you will face the critical issue of how to cover the costs of care. Even if you have health insurance, your coverage may not include some or all of the patient care costs associated with a clinical trial. This is because some health plans define clinical trials as “experimental” or “investigational” procedures. Because lack of coverage for these costs can keep people from enrolling in trials, the National Cancer Institute is working with major health plans and managed care groups to find solutions. In the meantime, there are strategies that may help you deal with cost and coverage barriers. This section answers frequently asked questions about insurance coverage for clinical trial participation and directs you to additional information resources. The material here is mainly concerned with treatment clinical trials, since other types of trials (prevention, screening, etc.) are newer and generally not covered by health insurance at all. However, this guide may become more relevant for prevention and other types of trials as these trials grow more common. If you do not have any health insurance, you may find this section helpful for understanding some of the costs that trials involve.

What Costs Do Trials Involve? Who Is Usually Responsible for Paying Them? There are two types of costs associated with a trial: patient care costs and research costs. Patient care costs fall into two categories: ·

Usual care costs, such as doctor visits, hospital stays, clinical laboratory tests, x-rays, etc., which occur whether you are participating in a trial or

Adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b.

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receiving standard treatment. These costs have usually been covered by a third-party health plan, such as Medicare or private insurance. ·

Extra care costs associated with clinical trial participation, such as the additional tests that may or may not be fully covered by the clinical trial sponsor and/or research institution.

The sponsor and the participant’s health plan need to resolve coverage of these costs for particular trials. Research costs are those associated with conducting the trial, such as data collection and management, research physician and nurse time, analysis of results, and tests purely performed for research purposes. Such costs are usually covered by the sponsoring organization, such as NCI or a pharmaceutical company.

Criteria Used by Health Plans to Make Reimbursement Decisions about Trials Health insurance companies and managed care companies decide which health care services they will pay for by developing coverage policy regarding the specific services. In general, the most important factor determining whether something is covered is a health plan’s judgment as to whether the service is established or investigational. Health plans usually designate a service as established if there is a certain amount of scientific data to show that it is safe and effective. If the health plan does not think that such data exist in sufficient quantity, the plan may label the service as investigational. Health care services delivered within the setting of a clinical trial are very often categorized as investigational and not covered. This is because the health plan thinks that the major reason to perform the clinical trial is that there is not enough data to establish the safety and effectiveness of the service being studied. Thus, for some health plans, any mention of the fact that the patient is involved in a clinical trial results in a denial of payment. Your health plan may define specific criteria that a trial must meet before extending coverage, such as the following:

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Sponsorship Some plans may only cover costs of trials sponsored by organizations whose review and oversight of the trial is careful and scientifically rigorous, according to standards set by the health plan.

Trial Phase and Type Some plans may cover patient care costs only for the clinical trials they judge to be “medically necessary” on a case-by-case basis. Trial phase may also affect coverage; for example, while a plan may be willing to cover costs associated with Phase III trials, which include treatments that have already been successful with a certain number of people, the plan may require some documentation of effectiveness before covering a Phase I or II trial. While health plans are interested in efforts to improve prevention and screening, they currently seem less likely to have a review process in place for these trials. Therefore, it may be more difficult to get coverage for the care costs associated with them. Some plans, especially smaller ones, will not cover any costs associated with a clinical trial. Policies vary widely, but in most cases your best bet is to have your doctor initiate discussions with the health plan. Cost “Neutrality” Some health plans may limit coverage to trials they consider cost-neutral (i.e., not significantly more expensive than the treatments considered standard). Lack of Standard Therapy Some plans limit coverage of trials to situations in which no standard therapy is available. Facility and Personnel Qualifications A health plan may require that the facility and medical staff meet specific qualifications to conduct a trial involving unique services, especially

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intensive therapy such as a bone marrow transplant chemotherapy with bone marrow/ stem cell rescue).

(high-dose

Clinical Trials and Medicare Coverage For up-to-date information about Medicare coverage of clinical trials, go to the Web site for the Centers for Medicaid & Medicare (http://www.hcfa.gov/coverage/8d.htm; formerly the Health Care Financing Administration). As of January 2001, the following information was accurate22:

What Will Medicare Pay? ·

Anything normally covered is still covered when it is part of a clinical trial. This includes test, procedures, and doctor visits that are ordinarily covered.

·

Anything normally covered even if it is a service or item associated with the experimental treatment. For example, Medicare will pay for the intravenous administration of a new chemotherapy drug being tested in a trial, including any therapy to prevent side effects from the new drug.

·

Anything normally covered even if it resulted from your being in the clinical trial. For example, a test or hospitalization resulting from a side effect of the new treatment that Medicare would ordinarily cover. What Costs Are Not Covered?

·

Investigational items or services being tested in a trial. Sponsors of clinical trials often provide the new drug free, but make sure you ask your doctor before you begin.

·

Items or services used solely for the data collection needs of the trial.

·

Anything being provided free by the sponsor of the trial.

On June 7, 2000, Present Clinton announced that Medicare would revise its payment policy to reimburse the routine patient care costs of clinical trials. The announcement is available for public viewing at the following Web address: http://www.cancer.gov/clinical_trials/doc.aspx?viewid=320DD013-BA7A-4177-A0002011089F34A0.

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What Kinds of Clinical Trials Are Covered? NCI’s Cancer Information Service has provided a fact sheet for Medicare beneficiaries at the following Web site: http://cis.nci.nih.gov/fact/8_14.htm. In general, cancer treatment and diagnosis trials are covered if: ·

They are funded by the National Cancer Institute (NCI), NCI-Designated Cancer Centers, NCI-Sponsored Clinical Trials Cooperative Groups and all other Federal agencies that fund cancer research. Other trials may be eligible for coverage and doctors can ask Medicare to pay the patients’ costs. Ask your doctor about this before you begin.

·

They are designed to treat or diagnose your cancer.

·

The purpose or subject of the trial is within a Medicare benefit category. For example, cancer diagnosis and treatment are Medicare benefits, so these trials are covered. Cancer prevention trials are not currently covered.

Increasing the Likelihood of Insurance Coverage for Trials23 There are several steps you can follow to deal with coverage issues up front when deciding to enter a clinical trial. Along the way, enlist the help of family members and your doctor or other health professionals. You may find the following checklist useful:

Understand the Costs Associated with the Trial Ask your doctor or the trial’s contact person about the costs that must be covered by you or your health plan. Are these costs significantly higher than those associated with standard care? Also, inquire about the experience of other patients in the trial. Have their plans paid for their care? Have there been any persistent problems with coverage? How often have the trial’s administrators been successful in getting plans to cover patient care costs?

This section has been adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b&docid=0df4397a-eccb-465f-bd33-a89e7a708c46.

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Understand Your Health Plan Be sure you know what’s in your policy; request and carefully review the actual contract language. If there’s a specific exclusion for “experimental treatment,” look closely at the policy to see how the plan defines such treatment and under what conditions it might be covered. If it is not clearly defined, call the plan’s customer service line, consult their Web site, and/or write to them. Ask for specific information about clinical trials coverage.

Work Closely with Your Doctor Talk with your doctor about the paperwork he or she submits to your health plan. If there have been problems with coverage in the past, you might ask your doctor or the hospital to send an information package to the plan that includes studies supporting the procedure’s safety, benefits, and medical appropriateness. This package might include: ·

Publications from peer-reviewed literature about the proposed therapy that demonstrate patient benefits;

·

A letter that uses the insurance contract’s own language to explain why the treatment, screening method, or preventive measure should be covered;

·

Letters from researchers that explain the clinical trial;

·

Support letters from patient advocacy groups.

Be sure to keep your own copy of any materials that the doctor sends to your health plan for future reference. Work Closely with Your Company’s Benefits Manager This person may be helpful in enlisting the support of your employer to request coverage by the health plan. Give Your Health Plan a Deadline Ask the hospital or cancer center to set a target date for the therapy. This will help to ensure that coverage decisions are made promptly.

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Know Your Rights24 A number of state governments are addressing the question of whether insurance companies ought to cover the costs associated with patients’ participation in clinical trials. Lack of such coverage is a significant barrier to many patients who might otherwise benefit from enrolling in a trial. Lack of coverage also makes it harder for researchers to successfully conduct trials that could improve prevention and treatment options. Information on State initiatives and legislation concerning cancer-related clinical trials is available at http://www.cancer.gov/ClinicalTrials/insurancelaws. By conducting your own research and learning about your rights, you may increase the likelihood that your insurance company will cover the costs of a trial.

If Your Insurance Claim Is Denied after the Trial Has Begun If a claim is denied, read your policy to find out what steps you can follow to make an appeal. In “What Cancer Survivors Need to Know about Health Insurance”, the National Coalition for Cancer Survivorship suggests that you and your doctor demonstrate to the health plan that: ·

The therapy is not just a research study, but also a valid procedure that benefits patients;

·

Your situation is similar to that of other patients who are participating in clinical trials as part of a covered benefit;

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Possible complications have been anticipated and can be handled effectively.

You also may wish to contact your state insurance counseling hotline or insurance department for more help, or write your state insurance commissioner describing the problem. Where Else Can I Turn for Assistance? It’s never easy to deal with financial issues when you or a loved one faces cancer. Unfortunately, costs can present a significant barrier to clinical trials participation. The range of insurance issues and health plan contracts makes it impossible to deal with all of them here. You may wish to consult this partial list of publications, organizations, and Web sites for more information: 24

Adapted from Cancer.gov: http://www.cancer.gov/ClinicalTrials/insurancelaws.

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Publications What Cancer Survivors Need to Know about Health Insurance National Coalition of Cancer Survivorship 1010 Wayne Avenue, 5th floor Silver Spring, MD 20910 (301) 650-8868 http://www.cansearch.org/ Cancer Treatments Your Insurance Should Cover The Association of Community Cancer Centers 11600 Nebel Street, Suite 201 Rockville, MD 20852 (301) 984-9496 http://www.accc-cancer.org/main2001.shtml The Managed Care Answer Guide Patient Advocate Foundation 739 Thimble Shoals Boulevard, Suite 704 Newport News, VA 23606 (757) 873-6668 E-mail: [email protected] 1998 Guide to Health Insurance for People with Medicare, The Medicare Handbook Medicare Helpline: 1-800-444-4606 Health Care Financing Administration: http://www.hcfa.gov/ New Medicare site: http://www.medicare.gov/ Assistance Programs Candlelighters Childhood Cancer Foundation Ombudsman Program 910 Woodmont Avenue, #4607 Bethesda, MD 20814 (301) 657-8401; 1-800-366-2223 (toll-free) E-mail: [email protected] http://www.candlelighters.org The Ombudsman Program helps families of children with cancer and survivors of childhood cancer resolve a range of problems, including insurance coverage difficulties. Local groups appoint a Parent Advocate who works with the treatment center on behalf of families.

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Medical Care Management Corporation 5272 River Road, Suite 650 Bethesda, MD 20816-1405 (301) 652-1818 email: [email protected] http://www.mcman.com/ Working for a range of clients, including health plans, employers, and patients, MCMC conducts independent, objective reviews of hightechnology medical care cases to assist in decision-making. While it does charge for its services, MCMC also offers a volunteer program for those who cannot afford to pay. More Information Resources OncoLink A service of the University of Pennsylvania Cancer Center. http://www.oncolink.com/ In addition to general cancer information, this web site features a section on financial information for patients. Among the topics: viatical settlements, life insurance, a glossary of financial and medical terms, and news about billing and insurance. American Association of Health Plans 1129 20th Street, NW, Suite 600 Washington, DC 20036-3421 (202) 778-3200 http://www.aahp.org/ The Web site section “For Consumers” includes a fact sheet on clinical research that describes various health plans’ efforts to support research initiatives and collaborate with academic health centers and universities. Health Insurance Association of America 555 13th Street, NW Washington, DC 20004 (202) 824-1600 ·

Home page: http://www.hiaa.org/

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Consumer Information: http://www.hiaa.org/consumer/

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Insurance Counseling Hotlines by State: http://www.hiaa.org/consumer/insurance_counsel.cfm

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State Insurance Departments: http://www.hiaa.org/consumer/state_insurance.cfm

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Government Initiatives to Expand Insurance Coverage for Trials25 The good news is that there has been a recent effort in the U.S. to assure clinical trials coverage, with NCI involved in several new initiatives as described below: NCI-Department of Defense Agreement An innovative 1996 agreement between NCI and the Department of Defense (DoD) has given thousands of DoD cancer patients more options for care and greater access to state-of-the-art treatments. Patients who are beneficiaries of TRICARE/CHAMPUS, the DoD’s health program, are covered for NCIsponsored Phase II and Phase III clinical treatment trials. NCI and DoD are refining a system that allows physicians and patients to determine quickly what current trials meet their needs and where they are taking place. NCI-Department of Veterans Affairs Agreement A 1997 agreement with the Department of Veterans Affairs provides coverage for eligible veterans of the armed services to participate in NCIsponsored prevention, diagnosis, and treatment studies nationwide. For additional information, see the VA/DoD Beneficiaries Digest Page at http://www.va.gov/cancer.htm.

Midwest Health Plans Agreement Some NCI Cooperative Groups have reached agreements with several insurers in Wisconsin and Minnesota to provide more than 200,000 people with coverage. This coverage is allocated for patient care costs if they participate in a cooperative group-sponsored trial.

Adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=1d92be79-8748-4bda-80052a56d332463b&docid=d8092601-daf9-4794-8536-3be2712eb6b9.

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Pediatric Cancer Care Network This network, a cooperative agreement among the Children’s Cancer Group, the Pediatric Oncology Group, and the Blue Cross Blue Shield System Association (BCBS) nationwide, will ensure that children of BCBS subscribers receive care at designated centers of cancer care excellence and may promote the enrollment of children in Cooperative Group clinical trials.

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “melanoma” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

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A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

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The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

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The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

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Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

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Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

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Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

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Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Acetaminophen: A drug that reduces pain and fever (but not inflammation). [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antigens: Substances that cause the immune system to make a specific immune response. [NIH] Antineoplastons: Substances isolated from normal human blood and urine being tested as a type of treatment for some tumors and AIDS. [NIH] Bevacizumab: A monoclonal antibody that may prevent the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Chondrosarcoma: A type of cancer that forms in cartilage. [NIH] Cisplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Corynebacterium: A genus of asporogenous bacteria that is widely distributed in nature. Its organisms appear as straight to slightly curved rods and are known to be human and animal parasites and pathogens. [NIH] Dacarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Dendritic: 1. branched like a tree. 2. pertaining to or possessing dendrites. [EU]

Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Flt3L: A drug that increases the number of immune cells and may stimulate the immune system to kill cancer cells. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH]

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Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Immunization: The induction of immunity. [EU] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Intravenous: IV. Into a vein. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Leukapheresis: Removal of the blood to collect specific blood cells; the remaining blood is returned to the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Melphalan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Necrosis: Refers to the death of living tissues. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH]

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Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pyrazoloacridine: An anticancer drug that belongs to the family of drugs called acridines. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recurrence: The return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Sarcoma: A cancer of the bone, cartilage, fat, muscle, blood vessels or other connective or supportive tissue. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] SU5416: An anticancer drug that belongs to the family of drugs called angiogenesis inhibitors. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Thalidomide: A drug that belongs to the family of drugs called angiogenesis inhibitors. It prevents the growth of new blood vessels into a solid tumor. [NIH] Transplantation: person. [NIH]

The replacement of an organ with one from another

Unresectable: Unable to be surgically removed. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vaccination: Treatment with a vaccine. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH]

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Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH]

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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on melanoma. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on melanoma. In Part II, as in Part I, our objective is not to interpret the latest advances on melanoma or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with melanoma is suggested.

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CHAPTER 4. STUDIES ON MELANOMA Overview Every year, academic studies are published on melanoma or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on melanoma. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on melanoma and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and melanoma, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the

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format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “melanoma” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

How to Diagnose Malignant Melanoma Source: Nurse Practitioner. 27(2): 26-27,31-35. February 2002. Summary: This journal article, a continuing nursing education activity, provides nurse practitioners with information on diagnosing malignant melanoma. The incidence of malignant melanoma has increased dramatically in recent decades. Malignant melanoma can either begin de novo or develop in association with a preexisting nevus. Although curable if caught early, malignant melanoma often presents a diagnostic challenge. Clinicians can use various methods, both old and new, to evaluate melanoma, including the ABCD method, total body photography, skin surface microscopy, and machine vision. The ABCD method involves evaluating a lesion for asymmetry, border, color variegation, and diameter. Benign nevi tend to be round and symmetric; have smooth, regular borders; be homogeneously colored; and be less than 6 millimeters in diameter. However, melanomas are often asymmetric; have irregular, uneven, and ragged edges; have multiple colors and various hues of light and dark brown, black, red, blue, or gray; and be larger than 6 millimeters in diameter. The inaccuracy of the ABCD method has prompted clinicians to use other modalities such as total body photography for high risk patients. Although potentially more accurate than the ABCD method, total body photography is still based on clinical visual inspection. In contrast, skin surface microscopy, also known as dermoscopy or epiluminescence microscopy, uses a handheld instrument to provide a 10 times illuminated view of the skin surface. This technique bridges clinical experience with histopathology. Learning dermoscopy requires understanding color, structures, and borders. Although skin surface microscopy improves diagnostic accuracy, it is labor intensive with a fairly high learning curve. Machine vision is a promising diagnostic tool that is being studied in various countries. This technique uses an electronic digital dermatoscopic camera to acquire and process images. A computer then segments the image, separating the boundaries of the pigmented lesion from the surrounding skin. The

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article discusses practice implications. 16 figures and 27 references. (AAM). ·

Skin Cancer Primer for Primary Care, A Source: JAAPA: Journal of the American Academy of Physician Assistants. 14(4): 13-14,16,21,22,25-26. April 2001. Summary: This journal article provides health professionals with information on the classification, diagnosis, and treatment of skin cancers. Skin cancers can be divided into nonmelanoma and melanoma. The nonmelanoma group comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Nonmelanoma cancers are highly treatable and rarely metastasize. Melanoma has a much higher mortality rate than nonmelanoma skin cancers. The number one risk factor for the development of premalignant and malignant skin neoplasms is sun exposure. Chronic sun exposure places a person at risk for actinic keratoses, BCC, and SCC. Episodic sunburns, particularly in childhood, increase the risk of malignant melanoma. Other risk factors include skin complexion, tolerance to sun exposure, ethnicity, degree of freckling, geographic location, history of malignant or premalignant skin lesions, exposure to ionizing radiation, chronic skin irritation, and immunosuppression. BBC is the most common skin cancer, and BBC lesions are typically located on the face and dorsum of the hands and forearms. BBC can be classified as nodulo ulcerative, superficial, morphealike, and pigmented. Definitive diagnosis requires a shave or full thickness punch biopsy. Therapeutic options for BBC depend on various factors, and they include electrodesiccation and curettage; Mohs' micrographic surgery; cryotherapy; and coned down, fractionated radiation therapy. SCC is the second most common cutaneous malignancy, occurring most frequently on sun exposed areas of the skin. The differential diagnosis includes actinic keratosis, Bowen's disease, keratoacanthoma, amelanotic melanoma, BCC, and verrucae. SCC is diagnosed with a full thickness punch biopsy. Therapeutic options include cryotherapy, excision with Mohs' micrographic surgery, and topical chemotherapy. Melanoma is a malignancy of melanocytes and nevus cells that appears clinically as a mole. The disease is evaluated on the basis of depth of invasion into the skin and thickness. A changing nevus is the most important sign or symptom for melanoma. Types include superficial spreading melanoma, nodulo ulcerative melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. Excision with narrow margins is the treatment of choice. 3 figures and 14 references.

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·

Skin Cancer Source: Postgraduate Medicine. 107(7): 225-226. June 2000. Summary: This journal article provides the general public and people who have skin cancer with information on this disease. The major types of skin cancer are basal cell carcinoma, squamous cell carcinoma, and melanoma. The basal cell and squamous cell types occur most often on areas of the skin that are regularly exposed to the sun. Melanoma tends to occur on areas of the body that are not regularly exposed to the sun. Signs of skin cancer include any changes in the size, color, shape, or texture of a mole; the development of a new mole; or any other unusual change in the skin. Risk factors include repeated exposure to bright sunlight, sunburn, use of skin creams or lotions that contain tar, exposure to organic arsenic, and exposure to radiation therapy or chemotherapy. The risk of skin cancer can be reduced by minimizing sun exposure; wearing sunglasses and protective clothing; using a sunscreen with both ultraviolet (UV) A and UVB protection; being careful on sand, snow, or water; avoiding artificial tanning devices; and taking special precautions with children. 1 figure.

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Early Detection and Treatment of Skin Cancer Source: American Family Physician. 62(2): 357-368. July 15, 2000. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 9066000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article provides health professionals with information on the early detection and treatment of skin cancer. The incidence of skin cancer is increasing by epidemic proportions. Basal cell cancer remains the most common skin neoplasm. This type of skin cancer may be classified as nodular, pigmented, cystic, sclerosing or morpheaform, superficial, or nevoid. Treatment of basal cell carcinoma with simple excision is generally curative. Squamous cell cancers may be preceded by actinic keratoses. These premalignant lesions are treated with cryotherapy, excision, curettage, or topical 5-fluorouracil. Squamous cell carcinoma, which is the second most common skin cancer, is usually the result of a high lifetime cumulative dose of solar radiation. Although squamous cell carcinoma is usually easily cured with local excision, it may invade deeper structures and metastasize. Aggressive local growth and metastasis are common features of malignant melanoma, which accounts for 75 percent of all deaths associated with skin cancer. Types of malignant melanoma include the superficial spreading type, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma.

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Early detection greatly improves the prognosis of patients with malignant melanoma. Although the differential diagnosis of pigmented lesions is challenging, the asymmetry, border irregularity, color variation, and diameter checklist and the seven-point checklist are helpful in determining which pigmented lesions require excision. Sun exposure remains the most important risk factor for all skin neoplasms. Thus, patients should be taught basic safe sun measures, including avoiding sun exposure during peak ultraviolet B hours, using sunscreens and protective clothing properly, and avoiding suntanning. 8 figures, 7 tables, and 32 references. (AA-M). ·

Preventing Mortality in Cutaneous Melanoma Source: Patient Care. 33(9): 34-36,39-40,43-44,46,49,56-58,60. May 15, 1999. Summary: This journal article provides health professionals with information on detecting early cutaneous melanomas. It addresses screening issues, describes the features of suspicious lesions, and presents methods of treating melanoma. The main early detection tools are screening by physicians and skin self-examination by patients. Although many medical organizations do not recommend routine screening for skin cancer, the American Academy of Dermatology, the American Cancer Society, the National Institutes of Health, and the Skin Cancer Foundation do recommend skin examination or annual screening. The risk level of a particular patient is an important factor in the decision to screen for melanoma. The most effective skin examination is comprehensive, and some experts recommend dermatologic photography as a supplement to total skin examination in high-risk patients. Tools that can help diagnose a suspicious lesion include optimal illumination, side-lighting, a hand lens, and a Wood's lamp. The types of melanoma are superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral-lentiginous melanoma. A biopsy is needed for all lesions meeting the ABCD (asymmetry, borders, color, diameter) criteria for melanoma. The histopathology report will indicate whether the lesion is benign or malignant. Treatment consists of surgical excision. Other treatments include chemotherapy for patients who have metastatic disease, liquid nitrogen cryosurgery, radiation therapy, and Mohs' micrographic surgery. Experimental therapies include melanoma vaccines and isolated limb perfusion. Involvement of regional lymph nodes is the most significant prognostic risk factor, followed by primary tumor thickness. The frequency of follow-up and the laboratory studies that should be obtained at each followup visit depend on the stage of disease and the risk of recurrence. Patient education is important in

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increasing the chances of early detection. 8 figures, 2 tables, and 11 references. ·

Pigment Clues Guide Melanoma Risk Diagnosis Source: Skin and Allergy News. 28(9):22; September 1997. Summary: This journal article for health professionals reports on the use of epiluminescence microscopy (ELM) for determining whether an equivocal lesion is melanoma. If a lesion seen with ELM has a pigment network with a fishnet or honeycomb pattern it is most likely melanocytic. In addition, other features that suggest a high, medium, or low risk of melanoma are identified.

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Melanoma: A Strategy For Detection And Treatment Source: Patient Care. 30(11):126-28, 30, 34-36, 41-42, 45, 48, 53; June 1995. Summary: This journal article examines the diagnosis and treatment options of skin cancer, including the types of drugs available, identification tips, and patient counseling. The authors discuss the difficulties in identifying suspicious growths on the skin; when an autopsy is needed; monitoring when a biopsy is inconclusive; prognostic indicators in cases of positive biopsies; the clinical staging examination; and available courses of action such as surgery, adjuvant therapy, palliative therapy, and experimental treatments. Concluding comments address long-term follow-up and patient counseling. 11 references, 2 figures, 3 tables.

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Vulvar Melanoma Source: Seminars in Dermatology. 15(1):67-70; March 1996. Summary: This journal article for health professionals discusses vulvar melanoma. Vulvar melanomas are seen in about three percent of all melanomas. The percentage reaches 10 percent of all malignant tumors of the vulva. The mean age of the patients is approximately 55 years. The first symptoms noticed by the patients are bleeding, pruritus, or a mass in the groin. Vulvar melanomas are mostly located at the labia minora. The differential diagnosis comprises different pigmented lesions, such as seborrheic keratosis, nevocellular nevus, lentigo, or hyperpigmentations of different origin. There is no typical histopathological pattern, but mostly melanomas of this site are of the mucosal-lentiginous type. In general, treatment consists of a complete excision for melanomas thinner than 1 millimeter and a wide excision for thicker melanomas. Recent investigations have shown the hemivulvectomies or vulvectomies do not produce a better survival rate. The question of a prophylactic ipsilateral

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lymph node dissection is not answered yet. The survival rates depend on the tumor thickness or the infiltration level. The importance of an early diagnosis should be stressed in vulvar melanomas, especially through an accurate inspection of the vulva at the time of a genital examination. In addition, vulvar self-examinations are an excellent possibility for early diagnosis, which allows definite treatment and vulvar conservation. 20 references, 4 figures, and 2 tables. (AA-M). ·

Be on the Lookout for Skin Cancer Source: AJN. 96(8):16 A, 16 C-16 D; August 1996. Summary: This journal article for health professionals provides guidelines for educating patients about avoiding damage from the sun that can cause skin cancer. Risk factors for developing skin cancer are outlined. The ABCD rule of skin assessment is explained. Features of basal and squamous cell carcinoma, melanoma, and actinic keratosis are presented. Components of a patient education session on skin cancer prevention are discussed, including providing patients with easy-tofollow instructions on skin self-examination, offering suggestions for ways of protecting the skin from sun exposure, and suggesting ways to effectively use screening agents. 6 references and 5 figures.

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Melanoma Information on the Internet: Often Incomplete: A Public Health Opportunity? Source: Journal of Clinical Oncology. 20(1):134-141, January 1, 2002. Summary: Researchers assessed the accuracy and completeness of information about melanoma that was retrievable by the use of search engines on the Internet. They utilized eight search engines: Yahoo, MSN, Lycos, Netscape, Go, Excite, Med Hunt, and Medical World Search. The first 30 uniform/universal resource locators (URL's) from each of the search engines using the search term melanoma were retrieved for evaluation of accuracy and completeness using a 35-point checklist rating system. The 35 items on the checklist were categorized into general information, risk factors, diagnosis, treatment, prevention, prognosis, and other factors. Searches identified 142 unique Web sites; of these, 74 could be accessed and were evaluated. Only 8 factors of 35 rating factors (24 percent) were present on at least half of the evaluated sites. The definition of melanoma occurred the most frequently, on 46 sites. Prognosis was the second most frequently included factor, mentioned on 44 sites. Factors related to prevention were present on approximately one third of the evaluated sites. Risk factors were mentioned in fewer than half the sites. Thirteen factual inaccuracies were found in 10 (14 percent) of the 74 sites. Most were relatively minor, with melanoma incidence being the most

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frequently stated inaccurate factor. Researchers conclude that melanoma Web sites retrieved by the search engines in this study often failed to mention much of the basic information pertaining to general aspects, risk factors, diagnosis, treatment, prevention, and prognosis. They recommend that health care providers recommend comprehensive and accurate Web sites for patients and work with their professional organizations to create complete and accurate Web sites. 6 tables, 40 references. ·

Ultraviolet A and Melanoma: A Review Source: Journal of the American Academy of Dermatology. 44(5):837-846, May 2001. Summary: The authors reviewed and discussed the issue of whether ultraviolet-A (UVA) radiation is a causative factor for human melanoma. The review (1) summarizes the characteristics of UVA and ultraviolet-B (UVB) radiation and their biological effects, (2) discuses scientific evidence that UVA radiation is a risk factor for melanoma, (3) discusses epidemiologic studies investigating UVA radiation and melanoma, and (4) discusses clinical evidence for UVA radiation being a risk factor for melanoma. The incidence and mortality rates of melanoma have increased during the past several decades in the United States. Among the reasons for these trends, increased exposure to UV radiation as a result of lifestyle changes, is generally recognized as an important factor. Sunburns have been identified as a risk factor for the development of melanoma. Because sunburns are primarily due to UVB radiation, which leads to chromosome damage, UVB is strongly absorbed by DNA, UVB radiation has been implicated as a major causative factor for melanoma. The role of UVA radiation as a possible etiologic factor for melanoma has received less attention, even though excessive sun exposure is also associated with excessive UVA exposure. UVA causes DNA damage through photosensitized reactions that lead to the production of reactive oxygen species. UVA has been shown to produce mutations in a variety of cultured cell lines. UVA radiation has been reported to produce melanomas and melanoma precursors in a hybrid fish and in the opossum. UVA radiation has also been reported to induce immunosuppression in laboratory animals and humans. Some, but not all, epidemiologic studies have reported an increase in melanoma incidence in users of sunbeds and sunscreens, and in patients undergoing psoralen and UVA therapy for psoriasis. The authors conclude that basic scientific evidence of the harmful effects of UVA radiation on DNA, cells, and animals exist. Collectively, these data suggest a potential role for UVA in the pathogenesis of melanoma. Evidence from epidemiologic and

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clinical studies is inconclusive but appears to be consistent with this view. 106 references. ·

Can Internet-based Continuing Medical Education Improve Physicians' Skin Cancer Knowledge and Skills? Source: Journal of General Internal Medicine. 16(1):50-56, January 2001. Summary: Researchers evaluated an Internet-based continuing medical education (CME) program designed to improve physicians' skin cancer knowledge and skill. The program, Melanoma Education for Primary Care (MEPC), provides an interactive, customized learning experience that incorporates well-established guidelines for recognizing melanoma. The program was provided through a commercial CME Web Site and through linkage with a commercial Internet medical portal. To receive CME credit, users had to complete a test before and after viewing the program. The tests were identical and consisted of 32 questions. Seven questions addressed confidence and attitudes (opinions), 10 rated general skin cancer knowledge, and 15 evaluated responses to clinical vignettes. In the vignettes, users were shown a picture of a lesion along with a brief clinical history and asked to decide whether the lesion should be biopsied or not. Of 691 Internet users who took the pretest, 354 stated that they were physicians and completed the entire program and posttest, and requested CME credit. This group was used as the study population in this analysis. Self-reported data on experience in dermatology revealed that 4 percent of the users had no dermatology training, 41 percent had received medical school lectures in dermatology, 24 percent had a residency or had received postgraduate dermatology lectures, 29 percent had experienced a rotation on a dermatology service, and 2 percent had completed a dermatology residency. Most (65 percent) of the users were in active primary care practice. After viewing MEPC, the physicians felt much more confident in their abilities to manage pigmented lesions, including melanoma. They showed generally more positive attitudes toward the role of primary care physicians and assessing the risk of skin cancer. Associated with improvements in confidence, users showed significant improvements in skin cancer knowledge after viewing the program, the overall percentage of correct answers increasing from 52 percent on the pretest to 85 percent on the posttest. Physicians in dermatology practice showed the highest pretest and posttest scores, 76 and 90 percent. Eighty-one percent of the vignettes were answered correctly on the pretest and 90 percent were answered correctly on the posttest. User satisfaction with the program was rated as extremely high. Researchers conclude that an easily distributed, online program can improve physician confidence and knowledge and, possibly, skills in

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managing skin cancer. This type of program could be beneficial because lack of confidence in identifying suspect lesions is a major barrier to primary care physicians performing skin cancer screening. 1 figure, 2 tables, 17 references. ·

Skin Cancer Primer for Primary Care Source: Journal of the American Academy of Physician Assistants. 14(4):13-26, April 2001. Summary: The author presents basic information on skin cancer for primary health care providers. It is one of a series of articles approved for category one continuing medical education (CME). The article (1) summarizes the epidemiologic aspects of the three types of skin cancer (basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma); (2) discusses ultraviolet radiation and other risk factors for skin cancer; and (3) presents clinical guidelines for diagnosing BCC, SCC, and melanoma. The article also summarizes guidelines to assist health care providers in counseling patients on skin cancer prevention. 3 figures, 14 references.

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Current Practice and Future Trends in Malignant Melanoma Source: Journal of the Louisiana State Medical Society. 153(4):191-197, April 2001. Summary: The author discusses current practices and future trends in diagnosing and treating malignant melanoma. The article (1) discusses risk factors for melanoma; (2) reviews standard approaches to preventing, diagnosing, staging, and treating melanoma; and (3) discusses new trends in melanoma care. A number of melanoma risk factors have been identified, including (1) red or blond hair; (2) family history of melanoma; (3) actinic keratoses; (4) pronounced freckling on upper back; (5) three or more blistering sunburns before age 20 years; and (6) 3 years or more of outdoor summer jobs during the teen years. The presence of one of the six risk factors confers a three-fold risk on a patient. If three or more risk factors are present, the risk increases 20-fold. The amount of sun exposure and sunburning are the only risk factors that can be modified. Melanomas have been traditionally staged using the American Joint Committee on Cancer system which considers (1) tumor stage, (2) regional lymph node analysis, (3) presence or absence of distant metastases, and (4) stage grouping. Excisional biopsy and chemotherapy have been standard treatments. New concepts in melanoma care include (1) sentinel lymph mapping, (2) immunotherapy, and (3) melanoma vaccines. The use of vaccines is considered one of the more exciting areas of melanoma research. Different types of vaccines have been tested, using

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autologous and allogenic whole melanoma cells or melanoma specific antigens such as peptides or gangliosides. Ganglioside GM2 is an example of a melanoma specific antigen used in vaccine therapy. Melanoma patients with natural antibodies to GM2 have been shown to have prolonged survival compared with those without the antibodies. Patients in whom GM2 antibodies can be stimulated also show improved survival. The article summarizes information on how melanoma patients in Louisiana can obtain information on clinical trials immunotherapy and chemoimmunotherapy. 1 table, 44 references.

Federally Funded Research on Melanoma The U.S. Government supports a variety of research studies relating to melanoma and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.26 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to melanoma and related conditions. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore melanoma and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for melanoma: ·

Project Title: A Model for Genetic Susceptibility: Melanoma Principal Investigator & Institution: Berwick, Marianne; Associate Attending Epidemiologist; Sloan-Kettering Institute for Cancer Res for Cancer Research New York, Ny 10021 Timing: Fiscal Year 2000; Project Start 0-SEP-1999; Project End 1-AUG2004

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Summary: Melanoma provides a unique model for studies of gene-gene and gene-environmental interaction in the development of cancer. It has several key features. First, there is a major environmental cause of melanoma, exposure to solar UV radiation, which may account for as much as 90 percent of cases in populations of European origin. Second, variants of or mutations in at least three classes of genes with very different functions may determine variation in melanoma risk-cell cycle genes, nucleotide excision repair genes and genes relating to cutaneous pigmentation. Third, the latter two classes of genes are involved in protection against the effects of UV radiation. These features permit the study of gene-gene and gene-environment interactions under circumstances largely free from confounding environmental factors and with genes whose functions and relationships to the environmental factor are reasonably well understood. We hypothesize that there are wide variations among individuals in terms of susceptibility to melanoma. This variation is probably influenced in a heterogeneous manner by multiple susceptibility genes, and sun exposure, the major known exogenous factor, may exert its influence interacting with these genes. Our proposed study will permit evaluation of the public health impact of genetic mutations and polymorphisms and their interaction with sun exposure, via estimation of relevant population parameters in a novel study design. In a large, international population-based case control study covering a wide range of latitudes, we will 1. Determine the relative risk for developing melanoma due to germline mutations and polymorphisms in the cell cycle genes, CDKN2A and CDK4. 2. Determine the relative risk for developing melanoma due to polymorphisms in the melanocortin receptor gene MC1R, a major pigmentary gene. 3. Determine the relative risk for developing melanoma due to allelic variation in the DNA repair genes that specialize in removing DNA damage due to UV radiation, the nucleotide excision repair genes (NER). 4. Analyze the interactions among genetic variants that are associated with the development of melanoma and their association with solar UV radiation. We will do this by way of a novel epidemiological design, a population-based case-control study in which the controls are subjects with incident primary melanoma and the cases are subjects diagnosed with a second or higher order primary melanoma. This design offers substantially greater statistical power to test our hypotheses than a classical case-control study with general population non-diseased control (Begg and Berwick 1997) and, in principle, higher participation rates by both cases and controls. It has substantial potential for application to other areas of cancer susceptibility. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Gene Therapy for Human Malignant Melanoma Principal Investigator & Institution: Grimm, Elizabeth A.; Professor; Introgen Therapeutics, Inc. 2250 Holcombe Blvd Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 2-JUL-2001; Project End 0-JUN2003 Summary: (Applicant's Description) Melanoma is the most malignant of skin cancers. In the USA, the incidence of melanoma is increasing more rapidly than any other cancer. Melanoma is the most frequently occurring cancer in women from the ages of 25-30, and has recently replaced leukemia as responsible for the most lost work hours in the United States. Currently there is no approved therapy that achieves more that a 20% response rate. Therefore, better therapies for malignant melanoma are urgently needed. Introgen Therapeutics is developing a novel anti-tumor gene therapeutic, Ad-mda7, and has demonstrated it's anti-tumor potential against breast and lung cancer cell lines. Here, we propose to perform proof-of-principle experiments to evaluate the efficacy of Ad-mda7 in melanoma. Growth inhibition studies will be performed using human melanoma cell lines in vitro and, if successful, will progress to evaluate Ad-mda7 in vivo using human melanoma xenografts. If these first aims are successful, we will test Ad-mda7 alone and in combination with conventional chemotherapeutic agents using metastatic tumor models. At the end of this Phase I STTR, we plan to have gathered the necessary efficacy data to proceed to safety studies and IND filing in a Phase II STTR, based on clinical trial testing of Ad-mda7. Proposed Commercial Application: Ad-mda7 is a gene therapy drug to be tested as a novel therapeutic for the treatment of malignant melanoma. Malignant melanoma is a dire skin cancer with few available treatment options. The incidence of melanoma and malignant melanoma is increasing. Approximately 41,000 people are predicted to diagnosed with melanoma this year, with more than 7,000 deaths resulting from this disease. The studies outlined here will guide the preclinical development of Ad-mda7 for melanoma. Subsequent Phase II studies will evaluate the therapeutic potential of Ad-mda7 in clinical trials with the goal of submission of a BLA to the FDA and subsequent marketing. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Metastasis

Immunologic

Control

of

Melanoma

Pulmonary

Principal Investigator & Institution: Donawho, Cherrie; Immunology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030

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Timing: Fiscal Year 2000; Project Start 1-APR-1997; Project End 1-JAN2002 Summary: Much of the effort in the immunotherapy of human cancer has focused on malignant melanoma. This is attributable to clinical observations suggesting that cutaneous melanomas are antigenic and to experimental studies demonstrating anti-melanoma immune responses in patients. In spite of the fact that melanomas may be among the most antigenic of human cancers, attempts to control this disease using immunological approaches have been disappointing because of an inability to completely eradicate melanoma metastases. We have developed a syngeneic murine model with which to investigate the reasons for the failure of immune mechanisms to control melanoma metastases. In this model, the growth and resection of local K1735-M2 melanoma tumors in syngeneic hosts leads to the development of a high level of systemic immunity, as indicated by the ability of the mice to reject subcutaneous challenge with melanoma cells. Nonetheless, many of these animals subsequently die from pulmonary metastases derived from the original immunizing inoculum. The objectives of the proposed studies are (a) to investigate, in a systematic way, the reasons for the failure of immune effector mechanisms to control pulmonary melanoma metastases and (b) to develop approaches for inducing effective T-cellmediated immunity in the lungs. For part (a) we will test three specific hypotheses: 1) Melanoma metastases have undergone immunoselection in vivo and are no longer recognized by immune effector cells. 2) Immune effector cells that reach the lungs fail to function in the pulmonary microenvironment, because if inhibitory substances produced by the lungs or by the melanoma metastases. 3) Immune effector cells induced by s.c. immunization fail to home to the lungs. For part (b), we will use a T- cell receptor transgenic mouse model to determine how to induce mucosal immunity that will provide an effective T-cell-mediated immune response in the pulmonary compartment. We will then test the hypothesis that induction of mucosal immunity provides better protection against pulmonary metastases than conventional s.c. immunization. These studies should provide insights as to why melanoma metastases escape from immunological control and may suggest new approaches for more effective immunotherapy of pulmonary metastases. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Increasing Effects of Interferons for Melanoma Principal Investigator & Institution: Borden, Ernest C.; Director; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195

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Timing: Fiscal Year 2002; Project Start 7-JAN-2002; Project End 1-DEC2005 Summary: New therapies to eliminate melanoma must be identified both for the high-risk patient after surgery and for metastatic disease. Interferons (IFNs) have therapeutic activity in both clinical settings but little expansion has occurred in understanding of mechanisms underlying clinical effectiveness in melanoma -- or indeed other malignancies. Underlying clinical antitumor effects must be the potent and pleiotropic gene modulatory effects that occur at a transcriptional level. Utilizing oligonucleotide array analysis, over 100 genes that are induced by IFNs in a melanoma cell line have been identified. On an equimolar basis these genes are induced to a substantially greater extent by IFN-beta than by IFN-alpha2. Based upon the hypothesis that the antitumor effects of IFNs in melanoma may result from direct effects on tumor cells, apoptosis, an understudied effect of IFNs, is a focus of our studies. Induction of apoptosis, coupled with array studies, led to the protein TRAIL (TNF-Related Apoptosis Inducing Ligand) as a mechanism that in part accounts for melanoma cell death. In sensitive melanoma cell lines, IFN-beta, but not IFN-alpha2, induces caspase dependent apoptosis that was associated with TRAIL. Resistant melanoma cell lines are characterized by lack of proliferative inhibition or apoptosis induction by either IFN- alpha2 or IFN-beta and lack of TRAIL induction. The data further suggest that apoptosis induction is negatively influenced by NFkappaB (Nuclear Factor kappa B) activation by TRAIL. With a goal of understanding of IFNs as antitumor cytokines and using melanoma as a model, our working hypothesis is that genes and functional mechanisms, yet to be identified, contribute substantially to the antitumor effects of IFNs. Our estimates based upon genome size suggest that greater than 500 interferon- stimulated genes (ISGs) remain to be identified. The goals of the proposal are: 1) By assessment of sensitive and resistant melanomas to identify new genes that may contribute to mediating apoptosis response and resistance in response to IFNs, 2) To define and confirm functional effects of the newly identified ISG, TRAIL, on IFN-induced apoptosis, 3) To determine how NF- kappaB or other induced anti-apoptotic pathways influence actions of IFNs and TRAIL, and 4) As an effective inducer of of apoptosis in mice and of TRAIL, to conduct a Phase II trial of IFN-beta to identify disease response in metastatic melanoma. The data should contribute to understanding of IFNs effects in melanoma but also other neoplasms and to a beginning understanding of the therapeutic potential of TRAIL. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Induction of Melanoma Immunity by Dendritic Cell Subsets Principal Investigator & Institution: Banchereau, Jacques F.; Director; Rockefeller University 66Th and York Ave New York, Ny 10021 Timing: Fiscal Year 2000; Project Start 0-SEP-2000; Project End 1-JUL-2004 Summary: Dendritic cells (DC) induce and sustain immune responses and are therefore excellent candidates for active immunization. DC comprise several subsets which may elicit different immune responses in vivo. Our in vitro studies show that both Langerhans cells (LC) and interstitial DC (intDC) are capable of inducing T cell proliferation. However, intDC are uniquely able to induce the differentiation of naive B cells. Though LC express unique properties, such as the presence of Birbeck granules, in vitro studies have not yet attributed a specialized biological function to LC. It is our hypotheses that LC are more efficient than intDC for stimulation of CD8 T cell responses. Because ex vivo cultures of CD34+ hematopoietic progenitors (HPC) yield both LC and intDC, while cultures of monocytes yield interstitial-like DC, we surmise that the presence of both DC subsets allows CD34+HPC-derived DC (cd34DC) to induce stronger immune responses than monocyte-derived DC (MDC). We will study the ability of different DC populations, loaded with melanoma antigens, to elicit melanoma-specific CD4 and CD8 T cell responses in stage IV melanoma. First, we will compare the in vitro immunogenicity of CD34DC and MDC loaded with either melanoma peptides or dying melanoma cells. Second, we will study melanomaspecific immune responses induced in vivo in a clinical trial where two groups of stage IV patients are randomized to receive either melanoma peptides loaded CD34DCs or melanoma peptides loaded MDC. This will allow us to study spreading of the responses beyond the peptides used for the immunization (epitope spreading). Our 4 aims can be summarized as follows: Aim 1: To determine the optimal conditions for the generation of mature CD34DC. Aim 2: To determine whether mature CD34DC induce stronger immune responses in vitro than mature MDC. Aim 3: To determine whether mature CD34DC induce immune responses in vivo than mature MDC. Aim 4: To determine epitope spreading and diversification of melanoma immunity in vitro. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Melanoma Chemoprevention Principal Investigator & Institution: Dellavalle, Robert P.; Dermatology; University of Colorado Hlth Sciences Ctr 4200 E 9Th Ave Denver, Co 80262

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Timing: Fiscal Year 2002; Project Start 1-JUN-2002; Project End 1-MAY2007 Summary: (provided by applicant): The incidence of cutaneous malignant melanoma is rising faster than any other cancer in the US. 1 in 74 Americans will develop melanoma, more than 45,000 cases will be diagnosed, and more than 7,500 Americans will die from melanoma this year. Effective prevention of melanoma will not only save lives, but will also decrease the estimated one billion dollars spent annually treating melanoma in the US. There is currently no recognized chemoprevention for melanoma. Two large, randomized, placebo-controlled clinical trials, the VA-HIT Study utilizing gemfibrozil, and the AFCAPS Study utilizing lovastatin, have each reported an association of lipid-lowering medication therapy with statistically significant lower melanoma incidence rates. Lovastatin inhibits melanoma cell growth in tissue culture, and mice Jed lovastatin develop lower lung metastases following tail vein injection with mouse B16 melanoma cells. More recently low concentrations of atorvastatin have been reported to specifically induce apoptosis and inhibit migration of human A375 melanoma cells but not cultured melanocytes. To investigate the unconventional hypothesis that lipid-lowering medications might prevent melanoma, a case-control study will be conducted utilizing Veterans Administration (VA) databases to answer the following question: Do persons who have developed cutaneous malignant melanoma have a history of less lipidlowering medication exposure than persons who are spared the disease? The answer to this question will help determine whether more expensive and labor intensive randomized prospective clinical trials of potentially teratogenic lipid-lowering medications should be initiated in persons at high risk of developing melanoma. Robert Dellavalle, MD, Ph.D., is an Assistant Professor of Dermatology at the University of Colorado Health Sciences Center and a staff dermatologist at the Denver VA medical center He is committed to a career in academic dermatology and public health. His current career goals are completing a Masters of Science in Public Health and becoming an independent researcher in skin cancer prevention and control. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Melanoma Control for Sibling of Melanoma Patients Principal Investigator & Institution: Gilchrest, Barbara A.; Professor and Chair; Dermatology; Boston University 121 Bay State Rd Boston, Ma 02215 Timing: Fiscal Year 2000; Project Start 0-APR-1998; Project End 1-JAN2002

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Summary: With low cost screening and preventive procedures readily available, no one should die of cutaneous melanoma. Promoting melanoma control for at risk populations through regular skin cancer screening and sun protection practices should counter this modern cancer epidemic. Siblings (and other first-degree relatives) of melanoma patients have a two - eight fold elevated relative risk of developing melanoma themselves but have suboptimal knowledge of their risk and limited practice of screening and prevention measures. To date, no intervention protocols have targeted this high risk sibling group, a population estimated to be up to three-quarters million or more Americans. The investigators propose a randomized trial testing personalized telephone counseling intervention support and screening (PERTCISS) that delivers melanoma risk information to siblings and promotes screening and prevention practices. They propose to intervene at a time of a new diagnosis of melanoma in a family member, capitalizing on this teachable moment to reach siblings. They will randomize 450 adult siblings (New England residents) of newly diagnosed melanoma patients to PERTCISS or standard care (SC). The specific aims are to determine, in siblings, the impact of PERTCISS compared to SC on melanoma screening and prevention practices, as well as the knowledge and attitudes that mediate and motivate these practices. They hypothesize that, compared to those in SC, siblings randomized to PERTCISS will demonstrate: 1) Higher levels of three practices: a) physician skin cancer screening examinations, b) skin self-examination for melanoma, c) sun protection practices; and 2) Higher levels of knowledge about melanoma risk and improved attitudes about early detection and prevention. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: P53 Function and Apoptosis in Melanoma Principal Investigator & Institution: Halazonetis, Thanos D.; Associate Professor; Wistar Institute 3601 Spruce St Philadelphia, Pa 19104 Timing: Fiscal Year 2002 Summary: (Applicant's Description) The p53 tumor suppressor gene induces cell cycle arrest and/or apoptosis when activated by DNA damage. Because cancer is treated with DNA-damaging agents, the outcome of therapy is significantly influenced by the ability of p53 to induce apoptosis in response to DNA damage. Thus, tumors that express wild-type p53 tend to respond better to therapy and are more radiosensitive than tumors expressing mutant inactive p53. One exception 5 melanoma; these tumors express wild-type p53, but are extremely radioresistant. Our goal is to understand at he molecular level why wild-type p53 does not induce apoptosis of melanoma cells with

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damaged DNA. In normal cells, p53-dependent apoptosis in response to DNA damage occurs in three steps: a) increase in the halffife of the p53 protein, leading to increased protein levels, and increase in the affinity of p53 for specific DNA sequences; b) binding of p53 to regulatory regions of specific genes and induction of transcription of these genes; ) induction of apoptosis by the protein products of the p53-inducible genes. Our preliminary results suggest that in melanoma cells, p53, even in the absence of DNA damage, has constitutively high affinity for DNA. We also Find a defect in the ability of p53 to activate transcription of specific target genes, such as the mdm2 gene. We therefore hypothesize that the radioresistance of melanoma is due to two molecular events that occur during Lransformation of mel anocytes to melanoma cells: a) an aberration in the DNA damage response leading to onstitutive activation of p53; and b) a defect in the ability of p53 to function as a transcription factor for the full repertoire of p53-target genes, allowing melanoma cells to escape apoptosis. To address this hypothesis we will:1) analyze the aberrant response of p53 to DNA damage during melanoma progression and determine whether it an be used as a diagnostic and prognostic marker; 2) determine whether a defect in the ability of p53 to induce expression of the full repertoire of p53-target genes underlies the escape of melanoma cells from p53-dependent apoptosis; and 3) determine whether altered DNA binding sequence-specificity and/or compromised transcriptional activity underlie the inability of p53 to induce expression of the full repertoire of p53-target genes. These experiments will help identify therapeutic strategies aimed at restoring apoptosis to melanoma cells. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Prediction and Modification of Melanoma Risk Principal Investigator & Institution: Guerry, Dupont; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 191046205 Timing: Fiscal Year 2000; Project Start 9-SEP-1997; Project End 0-JUN2002 Summary: Melanoma is a potentially lethal skin cancer. Its incidence and mortality rates are increasing faster than those of most other malignancies. The over-arching theme of this Program is melanocytic tumor progression, the process that epidemiologically, mechanistically, and clinically links environmental exposure, the precursor state, primary melanoma with and without invasive and metastatic potential, and metastasis. Our goal is to decrease mortality from melanoma, a malignancy for which there are compelling arguments for interventions

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directed to high risk cohorts and patients with primary disease. To achieve this, three projects will be focused on aspects of early tumor progression to: 1) define the mechanisms of and predict heightened melanoma susceptibility, 2) ameliorate this risk by rational chemoprevention, and 3) quantify the risk of metastasis in patients with primary disease to allow selection of patients for new staging procedures and adjuvant therapies. Project 1 is a case-control study that addresses the multifactorial etiology of melanoma. It asks whether candidate genotypes (ascertained from DNA self-collected using a non-invasive method) and other risk factors interact in and help explain melanoma etiology and whether these distinguish persons developing melanoma in a high risk cohort. This cohort is made up of individual s with nevi (dysplastic nevi) that are melanoma risk markers and potential precursors. Project 2 utilizes a randomized trial of topical tretinoin and 4HPR (fenretinide) to test chemoprevention in another cohort with dysplastic nevi. It uses clinical and histologic changes in these intermediate markers of tumor progression as the endpoints and will correlate the in situ expression and distribution of retinoid receptors with response and with markers of apoptosis and of tumor infiltrating lymphocyte (TIL) activity. Project 3 employs clinical and pathological data from a cohort of patients followed for 10 years as variables in the construction and validation of credible, accurate, and generalizable prognostic models. These are a prediction rule to identify nonmetastasizing lesions and a probability model to estimate individual risks of metastasis in patients with more advanced primaries. Variables include marker of melanoma cell proliferation and cytolytic TIL. These variables will also be studied in a prospective series to test as an independent variable an RT-PCR based assay for circulating melanoma cells (expression in blood of the gene for the pigment-related protein tyrosinase). To maximize productivity and efficiency the projects are served by three cores: a coordinating administrative Core, a Data Management and Analysis core, and a Pigmented Lesion Clinical/Pathology Core (PLCC). For more than 20 years the PLCC has ascertained and tracked over 4000 melanoma patients. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Retinoid in Chemoprevention of Primary Melanoma Principal Investigator & Institution: Halpern, Allan; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 191046205 Timing: Fiscal Year 2000 Summary: Melanoma incidence continues to rise at an alarming rate. Attempts to improve survival in patients with melanoma have focused

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on melanoma prevention and the detection of melanoma at a surgically curable stage. The identification of high risk cohorts and a well characterized sequence of melanoma tumor progression provide a framework for developing chemoprevention studies of melanoma. Dysplastic nevi are clinically and histologically defined "intermediate" lesions that are potential precursors of melanoma and markers of melanoma risk. Epidemiologic studies identify two subsets of individuals with dysplastic nevi that are at sufficiently high frisk for melanoma to warrant attempts at chemoprevention; individuals with dysplastic nevi and a personal history of melanoma and individuals with dysplastic nevi from familial melanoma families. We propose to conduct a multicenter, randomized clinical study of topical tretinoin and 4-HPR (fenretinide) for the chemoprevention of melanoma in conjunction with the Eastern cooperative Oncology Group (ECOG). The study population is a cohort of individuals with large numbers of dysplastic nevi and a personal or family history of melanoma. The study utilizes morphologic and histologic changes in dysplastic nevi as the clinical endpoint. We will provide morphological, pathological, photographic, and informatics expertise to the study by; 1) coordinating and standardizing photography, b) providing computer digitization and archiving of clinical images and analysis of the pre and post treatment clinical photographs, and c) providing expert processing and histological analysis of the excised nevi. We hypothesize that pharmacologic treatment with 4-HPR and/or tretinoin will result in a clinical improvement in dysplastic nevi and that this clinical response will be associated with histologic evidence of decreased numbers of lesional cells. We propose to classify the mechanisms involved in effecting this clinical response by measuring in-situ expression of markers of nevomelanocyte apoptosis, cytolytic immune cells, and nevomelanocyte retinoid receptor expression at multiple time points of therapy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Role of the PTEN Pathway in Melanoma Principal Investigator & Institution: Bosenberg, Marcus W.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 1-SEP-2001; Project End 0-JUN2002 Summary: (Applicant's Description): Melanoma is a common and potentially devastating disease. In the United States, 42,000 new cases and 7,300 deaths due to melanoma occurred in 1998. Histopathological criteria are the primary factors used to predict prognosis; however, for intermediate to thick tumors (>1.5 mm), the ability to accurately predict

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prognosis is poor. Early metastases characteristic of melanoma are an ominous sign, as current therapies have little effect on survival. The lack of accurate prognostic i n d icators and effective therapies emphasize the need for a better understanding of the genetic and phenotypic changes in melanoma formation and progression. The 9p21 locus containing the overlapping ink4a and arf genes is frequently mutated or deleted in familial and sporadic melanomas and acts as a tumor suppressor. 10q24, which contains the pten locus, is thought to be the site of a second melanoma tumor suppressor. A mouse model for melanoma has recently been developed in which mice deficient in ink4a/arf express an activated from of RAS in melanocytes. These mice form nodular melanomas that do not metastasize. My goal is to evaluate the role of the PTEN pathway in melanoma formation and progression using this mouse melanoma model as a starting point. First, the subcellular localization of the forkhead related (FKHR) transcription factors will be used to determine the status of PTEN pathway signaling in RAS/INK4a melanomas, as activation of PTEN pathway signaling results in a change from nuclear to cytoplasmic FKHR localization. In addition, RAS/INK4a melanomas will be evaluated for pten deletions and mutations. Second, the effect of pten loss on normal melanocyte biology and on melanoma formation and progression in RAS/INK4a mice will be examined by melanocyte-specific pten knockouts. Lastly, the model will be refined for analysis of the genetic and phenotypic changes of metastasis. The applicant is an M.D. who will have completed a residency in anatomic pathology and a fellowship in dermatopathology prior to the proposed start date. He has also completed Ph.D. training in cell biology. The proposed research will be carried out in the laboratory of Dr. Ronald DePinho at the Dana-Farber Cancer Institute, an affiliate of the Harvard Medical School. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Transcription Factor Ap2 in Metastasis of Melanoma Principal Investigator & Institution: Bar-Eli, Menashe; Associate Professor; Surgical Oncology & Cell Biol; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2000; Project Start 1-APR-1999; Project End 1-JAN2003 Summary: (adapted verbatim from investigator's abstract) The molecular changes associated with the transition of melanoma cells from radial growth phase (RGP) to vertical growth phase (VGP) (metastatic phenotype) are not very well defined. Recent work from this laboratory demonstrated that the expression of the cell surface adhesion molecule MCAM/MUC18, which belongs to the immunoglobulin superfamily,

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directly correlates with the metastatic potential of human melanoma cells. While none of the MCAM/MUC18-negative cell lines examined have been found to be metastatic, transfection of such cells with MCAM/MUC18 gene rendered them metastatic in nude mice. In addition, we have recently demonstrated that the progression of melanoma is associated with loss of expression of the c-KIT protooncogene tyrosine kinase receptor. Furthermore, re-expression of the cKIT receptor in highly metastatic cell lines inhibited their tumorigenicity and metastatic potential in nude mice. Indeed, exposure of c-KIT-positive melanoma cells in vitro and in vivo to stem cell factor (SCF), the ligand for c-KIT, triggered apoptosis of these cells but not of normal melanocytes. The mammalian transcription factor AP-2 is a sequencespecific DNA-binding protein expressed in neural crest lineages and regulated by retinoic acid. Our preliminary data indicate that both MCAM/MUC18 and c-KIT gene expression is highly regulated by AP-2. In addition, other genes that are involved in the progression of melanoma such as MMP-2, bel-2, E-cadherin, and p21/WAF-1 are also regulated by the transcription factor AP-2. Our laboratory has recently made the observation that while several nonmetastatic melanoma cell lines express AP-2, the highly metastatic cell lines do not express this transcription factor. Therefore, we hypothesize that loss of AP-2 expression may be a crucial event in the development of malignant melanoma. We are therefore proposing the three Specific Aims: 1) to provide a direct evidence for the involvement of AP-2 in the acquisition of the metastatic phenotype by transfecting metastatic cells with w.t. AP-2 and primary melanoma cells with a dominant negative AP-2B genes and subsequently analyze their tumorigenicity and metastatic potential in nude mice. 2) To study the effect of AP-2 and AP-2B on the expression of the above mentioned genes. 3) To evaluate the status of AP-2 expression and function in tumor specimens from patients in well-characterized melanoma database. These experiments will generate valuable information on the progression of melanoma, and help to develop new molecular staging markers and a common target for antitumor/metastasis therapy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: H2 Alpha Galactosyl Epitopes and Tumor Metastases Principal Investigator & Institution: Gorelik, Elieser; None; University of Pittsburgh at Pittsburgh 4200 5Th Ave Pittsburgh, Pa 15260 Timing: Fiscal Year 2000; Project Start 1-SEP-1997; Project End 0-JUN2002

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Summary: (adapted from the investigator's abstract) The applicants have found that highly metastatic melanomas of C57BL/6 mice (BL6, JB/RH and JB/MS) do not express H-2Kb molecules and 1-galactosyl epitopes but express a common melanoma associated antigen (MAA) encoded by an ecotropic C-type retrovirus produced by these melanomas. It remains unknown why several independently arising melanomas manifest similar phenotypic properties. The finding of a novel melanomaassociated ecotropic retrovirus raises the question whether the retrovirus might play a role in melanoma formation or regulation of metastatic and phenotypic properties of melanoma cells. Our data showed that infection of cultured normal melanocytes from C57BL/6 and B10BR mice with ecotropic retrovirus derived from BL6 melanoma resulted in their malignant transformation. As a continuation of the previous investigations, they propose to explore the following working hypothesis: ecotropic retroviruses emerged in normal melanocytes might induce their malignant transformation by insertion into particular chromosomal locations, affecting the expression of some proto-oncogenes or tumor suppressor genes as well as genes controlling metastatic properties of melanoma cells. The major objectives of the proposed studies are to analyze the mechanism determining common phenotypic properties found in melanomas of C57BL/6 and to identify genes that are affected by insertional mutagenesis, that might play a role in melanoma formation and progression toward the metastatic phenotype. They will analyze the role of melanoma-associated ecotropic retroviruses in the pathogenesis of murine melanomas, by assessing their ability to induce melanomas or accelerate DMBA/croton oil induced melanoma formation. The metastatic properties of novel carcinogen-or retrovirusinduced melanomas as well as the mechanisms responsible for loss of H2 class I molecules and alpha-galactosyl epitopes and TIMP-1 gene expression will be investigated. They will sequence the ecotropic retrovirus containing cosmid clones of the BL6 melanoma genomic library and identify genes affected by retrovirus insertion. Comparative analysis of expression of these genes in melanoma and normal melanocytes will be performed. This study might provide insights into the genetic basis of melanoma formation and metastatic progression. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: HLA Class I Allospecificity Abnormalities in Melanoma Principal Investigator & Institution: Ferrone, Soldano; Member and Chairman; Roswell Park Cancer Institute Corp Elm & Carlton Sts Buffalo, Ny 14263

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Timing: Fiscal Year 2000; Project Start 1-MAR-1996; Project End 5-JUL2001 Summary: A review of the literature has shown that immunohistochemical staining with mAb to monomorphic determinants of HLA Class I antigens has not detected HLA Class I antigens in about 20% of 275 primary lesions and in about 40% of 355 metastatic lesions. These abnormalities are associated with a poor clinical course of the disease. Furthermore, they may have a negative impact on the efficacy of active specific immunotherapy, since they provide melanoma cells with a mechanism to escape from destruction by HLA Class I restricted cytotoxic T cells recognizing melanoma associated antigens (MAA). Recent studies with a limited number of melanoma lesions have found a selective loss of HLA Class I allospecificities in melanoma lesions without detectable abnormalities in the staining by mAb to monomorphic determinants.- Therefore,-it is our-working hypothesis that thefrequency of abnormalities -in-HLA Class -I antigen expression in melanoma lesions is higher than that reported in the literature, since the published studies performed with mAb to monomorphic determinants of HLA Class I antigens have not detected selective losses of HLA Class I allospecificities. Furthermore, it is our working hypothesis that selective loss of HLA Class I allospecificities may account for resistance to lysis by cytotoxic T cells recognizing MAA of melanoma cells without detectable abnormalities in the reactivity with mAb to monomorpnic determinants of HLA Class I antigens, since the lost HLA Class I allospecificity is the immunodominant restricting element. Lastly, it is our working hypothesis that resistance to lysis by autologous cytotoxic T cells because of selective loss of a HLA Class I allospecificity may account for i) poor prognosis in patients without detectable abnormalities in the reactivity of their melanoma lesions with mAb to monomorphic determinants of HLA Class I antigens and ii) lack of efficacy of active specific immunotherapy with peptides presented in the context of the lost HLA Class I allospecificity. The goal of this application is i) to investigate the frequency of the selective loss of HLA Class I allospecificities in melanoma lesions ii) to assess the role of selective loss of HLA Class I allospecificities in the resistance of melanoma cells to lysis by autologous cytotoxic T cells recognizing MAA and in the clinical course of the disease, and iii) to characterize the molecular mechanisms underlying the selective loss of HLA Class I allospecificities. The information resulting from the outlined studies will be utilized to design the strategy to screen melanoma lesions for selective loss of HLA Class I allospecificities and to develop approaches to correct these abnormalities. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine. The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to the public.27 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with melanoma, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “melanoma” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “melanoma” (hyperlinks lead to article summaries): ·

123I- N-(2-diethylaminoethyl)-2-iodobenzamide: a potential imaging agent for cutaneous melanoma staging. Author(s): Moins N, D'Incan M, Bonafous J, Bacin F, Labarre P, Moreau MF, Mestas D, Noirault E, Chossat F, Berthommier E, Papon J, Bayle M, Souteyrand P, Madelmont JC, Veyre A. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 November; 29(11): 1478-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12397467&dopt=Abstract

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18-FDG PET scan in the staging of recurrent melanoma: additional value and therapeutic impact. Author(s): Stas M, Stroobants S, Dupont P, Gysen M, Hoe LV, Garmyn M, Mortelmans L, Wever ID. Source: Melanoma Research. 2002 September; 12(5): 479-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12394190&dopt=Abstract

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A human endogenous retroviral sequence encoding an antigen recognized on melanoma by cytolytic T lymphocytes. Author(s): Schiavetti F, Thonnard J, Colau D, Boon T, Coulie PG. Source: Cancer Research. 2002 October 1; 62(19): 5510-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12359761&dopt=Abstract

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A long-term analysis of 1018 patients with melanoma by classic Cox regression and tree-structured survival analysis at a major referral center: Implications on the future of cancer staging. Author(s): Averbook BJ, Fu P, Rao JS, Mansour EG. Source: Surgery. 2002 October; 132(4): 589-602; Discussion 602-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12407342&dopt=Abstract

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A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, temozolomide, interleukin 2, and IFN-alpha 2B in patients with metastatic melanoma. Author(s): Atkins MB, Gollob JA, Sosman JA, McDermott DF, Tutin L, Sorokin P, Parker RA, Mier JW. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 October; 8(10): 3075-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12374674&dopt=Abstract

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A phase II study of outpatient subcutaneous histamine dihydrochloride, interleukin-2 and interferon-alpha in patients with metastatic melanoma. Author(s): Schmidt H, Larsen S, Bastholt L, Fode K, Rytter C, Von Der Maase H. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 December; 13(12): 1919-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12453861&dopt=Abstract

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A randomized phase II study of two schedules of bryostatin-1 (NSC339555) in patients with advanced malignant melanoma: A National Cancer Institute of Canada Clinical Trials Group study. Author(s): Tozer RG, Burdette-Radoux S, Berlanger K, Davis ML, Lohmann RC, Rusthoven JR, Wainman N, Zee B, Seymour L.

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Source: Investigational New Drugs. 2002 November; 20(4): 407-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12448658&dopt=Abstract ·

Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients. Author(s): George R, Weightman W, Russ GR, Bannister KM, Mathew TH. Source: The Australasian Journal of Dermatology. 2002 November; 43(4): 269-273. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12423433&dopt=Abstract

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Adenosine receptors as mediators of both cell proliferation and cell death of cultured human melanoma cells. Author(s): Merighi S, Mirandola P, Milani D, Varani K, Gessi S, Klotz KN, Leung E, Baraldi PG, Borea PA. Source: The Journal of Investigative Dermatology. 2002 October; 119(4): 923-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12406340&dopt=Abstract

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Adenoviral vectors with E1A regulated by tumor-specific promoters are selectively cytolytic for breast cancer and melanoma. Author(s): Zhang L, Akbulut H, Tang Y, Peng X, Pizzorno G, Sapi E, Manegold S, Deisseroth A. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2002 September; 6(3): 386-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12231175&dopt=Abstract

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Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: results of a randomized trial. Author(s): Hersey P, Coates AS, McCarthy WH, Thompson JF, Sillar RW, McLeod R, Gill PG, Coventry BJ, McMullen A, Dillon H, Simes RJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 October 15; 20(20): 4181-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12377961&dopt=Abstract

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Agonists of peroxisome proliferator-activated receptor gamma inhibit cell growth in malignant melanoma.

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Author(s): Mossner R, Schulz U, Kruger U, Middel P, Schinner S, Fuzesi L, Neumann C, Reich K. Source: The Journal of Investigative Dermatology. 2002 September; 119(3): 576-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12230498&dopt=Abstract ·

Alteration of chromosome 9p21 and/or p16 in benign and dysplastic nevi suggests a role in early melanoma progression (United States). Author(s): Tran TP, Titus-Ernstoff L, Perry AE, Ernstoff MS, Newsham IF. Source: Cancer Causes & Control : Ccc. 2002 September; 13(7): 675-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12296515&dopt=Abstract

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Ambiguity in the U.K. guidelines for the management of cutaneous melanoma. Author(s): Ali FS, Harris PA, Butler PE. Source: The British Journal of Dermatology. 2002 October; 147(4): 835-6; Discussion 836-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12366457&dopt=Abstract

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Ambiguity in the UK guidelines for the management of cutaneous melanoma. Author(s): Ali FS, Harris PA, Butler PE. Source: British Journal of Plastic Surgery. 2002 July; 55(5): 452. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12372383&dopt=Abstract

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Amelanotic subungual melanoma mimicking pyogenic granuloma in the hand. Author(s): Harrington P, O'Kelly A, Trail IA, Freemont AJ. Source: Journal of the Royal College of Surgeons of Edinburgh. 2002 August; 47(4): 638-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12363192&dopt=Abstract

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An assessment of the CDKN2A variant Ala148Thr as a nevus/melanoma susceptibility allele. Author(s): Bertram CG, Gaut RM, Barrett JH, Pinney E, Whitaker L,

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Turner F, Bataille V, Dos Santos Silva I, J Swerdlow A, Bishop DT, Newton Bishop JA. Source: The Journal of Investigative Dermatology. 2002 October; 119(4): 961-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12406345&dopt=Abstract ·

Analysis of losses of heterozygosity of the candidate tumour suppressor gene DMBT1 in melanoma resection specimens. Author(s): Deichmann M, Mollenhauer J, Helmke B, Thome M, Hartschuh W, Poustka A, Naher H. Source: Oncology. 2002; 63(2): 166-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12239452&dopt=Abstract

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Analysis of mutations in the p16/CDKN2A gene in sporadic and familial melanoma in the Polish population. Author(s): Lamperska K, Karezewska A, Kwiatkowska E, Mackiewicz A. Source: Acta Biochimica Polonica. 2002; 49(2): 369-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12362978&dopt=Abstract

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Angioarchitecture of primary oral malignant melanomas. Author(s): Lee YJ, Nagai N, Siar CH, Nakano K, Nagatsuka H, Tsujigiwa H, Roan CH, Gunduz M. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2002 November; 50(11): 1555-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12417622&dopt=Abstract

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Angiotropism in cutaneous melanoma: a prognostic factor strongly predicting risk for metastasis. Author(s): Barnhill R, Dy K, Lugassy C. Source: The Journal of Investigative Dermatology. 2002 September; 119(3): 705-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12230518&dopt=Abstract

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Anorectal melanoma: successful treatment by surgical excision and combination chemoimmunotherapy. Author(s): Terada R, Ito S, Kobayashi M, Akama F, Tsujimura M, Ooe H.

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Source: Hepatogastroenterology. 2002 November-December; 49(48): 15458. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12397731&dopt=Abstract ·

Antibody-based vaccines for the treatment of melanoma. Author(s): Lutzky J, Gonzalez-Angulo AM, Orzano JA. Source: Seminars in Oncology. 2002 October; 29(5): 462-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12407511&dopt=Abstract

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Antigenicity and immunogenicity of Melan-A/MART-1 derived peptides as targets for tumor reactive CTL in human melanoma. Author(s): Romero P, Valmori D, Pittet MJ, Zippelius A, Rimoldi D, Levy F, Dutoit V, Ayyoub M, Rubio-Godoy V, Michielin O, Guillaume P, Batard P, Luescher IF, Lejeune F, Lienard D, Rufer N, Dietrich PY, Speiser DE, Cerottini JC. Source: Immunological Reviews. 2002 October; 188(1): 81-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12445283&dopt=Abstract

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Azoospermia in a patient receiving interferon alpha for a stage III melanoma. Author(s): Longo I, Sanchez-Mateos P, Lazaro P, Longo N. Source: Acta Dermato-Venereologica. 2002; 82(5): 389-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12430747&dopt=Abstract

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Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. Author(s): Widlund HR, Horstmann MA, Price ER, Cui J, Lessnick SL, Wu M, He X, Fisher DE. Source: The Journal of Cell Biology. 2002 September 16; 158(6): 1079-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12235125&dopt=Abstract

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Biochemotherapy for advanced melanoma. Author(s): Keilholz U, Gore ME.

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Source: Seminars in Oncology. 2002 October; 29(5): 456-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12407510&dopt=Abstract ·

Biochemotherapy of melanoma. Author(s): Flaherty LE, Gadgeel SM. Source: Seminars in Oncology. 2002 October; 29(5): 446-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12407509&dopt=Abstract

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Biochemotherapy of metastatic malignant melanoma. On downregulation of CD28. Author(s): Hakansson A, Hakansson L, Gustafsson B, Krysander L, Rettrup B, Ruiter D, Bernsen MR. Source: Cancer Immunology, Immunotherapy : Cii. 2002 November; 51(9): 499-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12357321&dopt=Abstract

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Biopsy techniques. Diagnosis of melanoma. Author(s): Swanson NA, Lee KK, Gorman A, Lee HN. Source: Dermatologic Clinics. 2002 October; 20(4): 677-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12380054&dopt=Abstract

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Brain metastases in melanoma: a European perspective. Author(s): Cattell E, Kelly C, Middleton MR. Source: Seminars in Oncology. 2002 October; 29(5): 513-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12407516&dopt=Abstract

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BRCA2 mutations in a population-based series of patients with ocular melanoma. Author(s): Scott RJ, Vajdic CM, Armstrong BK, Ainsworth CJ, Meldrum CJ, Aitken JF, Kricker A. Source: International Journal of Cancer. Journal International Du Cancer. 2002 November 10; 102(2): 188-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12385017&dopt=Abstract

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Capacity of murine IL-12 to inhibit the development of primary melanoma tumors and to prevent lung metastases in the melanoma-

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challenged mice. Author(s): Shrayer DP, Bogaars H, Cole B, Wolf SF, Wanebo HJ. Source: Journal of Experimental Therapeutics & Oncology. 2002 MarchApril; 2(2): 93-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12415625&dopt=Abstract ·

Capsaicin regulates vascular endothelial cell growth factor expression by modulation of hypoxia inducing factor-1alpha in human malignant melanoma cells. Author(s): Patel PS, Yang S, Li A, Varney ML, Singh RK. Source: Journal of Cancer Research and Clinical Oncology. 2002 September; 128(9): 461-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12242509&dopt=Abstract

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Cell cycle in sporadic melanoma. Author(s): Czajkowski R, Drewa T, Wozniak A, Krzyzynska-Malinowska E. Source: International Journal of Dermatology. 2002 September; 41(9): 5506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12358822&dopt=Abstract

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Cell-surface proteolysis, growth factor activation and intercellular communication in the progression of melanoma. Author(s): Bogenrieder T, Herlyn M. Source: Critical Reviews in Oncology/Hematology. 2002 October; 44(1): 1-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12398996&dopt=Abstract

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Chemoimmunohormonal therapy with carmustine, dacarbazine, cisplatin, tamoxifen, and interferon for metastatic melanoma: a prospective phase II study. Author(s): Stein ME, Bernstein Z, Tsalic M, Drumea K, Steiner M, Sklar Z, Haim N. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 October; 25(5): 460-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12393984&dopt=Abstract

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Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma. Author(s): Pyrhonen S, Hahka-Kemppinen M, Muhonen T, Nikkanen V, Eskelin S, Summanen P, Tarkkanen A, Kivela T. Source: Cancer. 2002 December 1; 95(11): 2366-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12436444&dopt=Abstract

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Chemotherapy approaches to melanoma. Author(s): Pavlick AC. Source: Dermatologic Clinics. 2002 October; 20(4): 709-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12380057&dopt=Abstract

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Clear cell sarcoma (malignant melanoma of soft parts): case report and review of the literature. Author(s): Hermann G, Klein MJ, Springfield DS, Abdelwahab IF. Source: Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes. 2002 October; 53(4): 237-40. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12391930&dopt=Abstract

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Clinical evaluation of 5-S-cysteinyldopa testing using a new and optimized detection system as a tumour marker for malignant melanoma. Author(s): Meyer T, Hauschild A, Kromminga A, Hartleb J, Arndt R, Christophers E, Stockfleth E. Source: Melanoma Research. 2002 September; 12(5): 471-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12394189&dopt=Abstract

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Cloning and characterization of the expression pattern of a novel splice product MIA (splice) of malignant melanoma-derived growthinhibiting activity (MIAY CD-RAP). Author(s): Hau P, Wise P, Bosserhoff AK, Blesch A, Jachimczak P, Tschertner I, Bogdahn U, Apfel R.

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Source: The Journal of Investigative Dermatology. 2002 September; 119(3): 562-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12230496&dopt=Abstract ·

Computer-aided melanoma diagnosis. Author(s): Elbaum M. Source: Dermatologic Clinics. 2002 October; 20(4): 735-47, X-Xi. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12380061&dopt=Abstract

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Contradiction of clinical expectations in lymphoscintigraphy sentinel node mapping in detecting microscopic melanoma metastasis. Author(s): Chang JW, Chiang HF, Lo YF, Chen CH, Kao PF. Source: Chang Gung Med J. 2002 July; 25(7): 474-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12350035&dopt=Abstract

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Critical appraisal of IFN-alpha-based adjuvant therapy in stage II-III malignant melanoma. Author(s): Eggermont AM. Source: Expert Rev Anticancer Ther. 2002 October; 2(5): 563-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12382524&dopt=Abstract

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Cucurbitacins from Trichosanthes kirilowii as the inhibitory components on tyrosinase activity and melanin synthesis of B16/F10 melanoma cells. Author(s): Oh H, Mun YJ, Im SJ, Lee SY, Song HJ, Lee HS, Woo WH. Source: Planta Medica. 2002 September; 68(9): 832-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12357397&dopt=Abstract

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Cutaneous malignant melanoma. Author(s): Podczaski E, Cain J. Source: Clinical Obstetrics and Gynecology. 2002 September; 45(3): 83043. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12370625&dopt=Abstract

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Cytomorphologic features of fine-needle aspiration of metastatic and recurrent melanoma. Author(s): Saqi A, McGrath CM, Skovronsky D, Yu GH. Source: Diagnostic Cytopathology. 2002 November; 27(5): 286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12411994&dopt=Abstract

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Cytotoxic T-lymphocyte responses in melanoma through in vitro stimulation with the Melan-A peptide analogue A27L: a qualitative analysis. Author(s): Palermo B, Campanelli R, Garbelli S, Mantovani S, Robustelli Della Cuna G, Necker A, Manganoni AM, Carella G, Rivoltini L, Lantelme E, Giachino C. Source: Melanoma Research. 2002 September; 12(5): 491-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12394191&dopt=Abstract

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Cytotoxicity of dopamine-derived tetrahydroisoquinolines on melanoma cells. Author(s): De Marco F, Perluigi M, Marcante ML, Coccia R, Foppoli C, Blarzino C, Rosei MA. Source: Biochemical Pharmacology. 2002 November 15; 64(10): 1503-1512. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12417263&dopt=Abstract

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Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival. Author(s): Smith SL, Damato BE, Scholes AG, Nunn J, Field JK, Heighway J. Source: British Journal of Cancer. 2002 November 18; 87(11): 1308-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12439722&dopt=Abstract

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Dermoscopy in melanoma screening. Author(s): Schneider R. Source: Archives of Dermatology. 2002 October; 138(10): 1378-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12374550&dopt=Abstract

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Desmoplastic and spindle cell melanomas express protein markers of the neural crest but not of later committed stages of Schwann cell differentiation. Author(s): Huttenbach Y, Prieto VG, Reed JA. Source: Journal of Cutaneous Pathology. 2002 October; 29(9): 562-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12358815&dopt=Abstract

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Desmoplastic malignant melanoma of the lip: A report of 6 cases and review of the literature. Author(s): Hui JI, Linden KG, Barr RJ. Source: Journal of the American Academy of Dermatology. 2002 December; 47(6): 863-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12451370&dopt=Abstract

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Desmoplastic neurotropic melanoma of the head and neck: The role of radiation therapy. Author(s): Anderson TD, Weber RS, Guerry D, Elder D, Schuchter L, Loevner LA, Rosenthal DI. Source: Head & Neck. 2002 December; 24(12): 1068-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12454945&dopt=Abstract

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Determination of potential adjuvant systemic therapy benefits for patients with resected cutaneous melanomas. Author(s): Thome SD, Loprinzi CL, Heldebrant MP. Source: Mayo Clinic Proceedings. 2002 September; 77(9): 913-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12233924&dopt=Abstract

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Development of a melanoma-specific adenovirus. Author(s): McCart JA, Wang ZH, Xu H, Hu Y, Park B, Alexander HR, Bartlett DL. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2002 October; 6(4): 471-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12377188&dopt=Abstract

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Development of an arterial tree in C6 gliomas but not in A375 melanomas. Author(s): Papoutsi M, Othman-Hassan K, Christ B, Patel K, Wilting J.

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Source: Histochemistry and Cell Biology. 2002 September; 118(3): 241-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12271360&dopt=Abstract ·

Diagnosing breast cancer with synchronous metastatic melanoma. Author(s): Bond LK, Vance R. Source: Cancer Practice. 2002 September-October; 10(5): 224-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12236834&dopt=Abstract

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Different h2 receptor antihistamines dissimilarly retard the growth of xenografted human melanoma cells in immunodeficient mice. Author(s): Szincsak N, Hegyesi H, Hunyadi J, Falus A, Juhasz I. Source: Cell Biology International. 2002; 26(9): 833-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12377215&dopt=Abstract

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Differential expression of thrombospondin 2 in primary and metastatic malignant melanoma. Author(s): Kunz M, Koczan D, Ibrahim SM, Gillitzer R, Gross G, Thiesen HJ. Source: Acta Dermato-Venereologica. 2002; 82(3): 163-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12353704&dopt=Abstract

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DNA repair gene XRCC3 241Met variant is not associated with risk of cutaneous malignant melanoma. Author(s): Duan Z, Shen H, Lee JE, Gershenwald JE, Ross MI, Mansfield PF, Duvic M, Strom SS, Spitz MR, Wei Q. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 October; 11(10 Pt 1): 1142-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12376526&dopt=Abstract

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Docetaxel in combination with dacarbazine in patients with advanced melanoma. Author(s): Bafaloukos D, Aravantinos G, Fountzilas G, Stathopoulos G, Gogas H, Samonis G, Briasoulis E, Mylonakis N, Skarlos DV, Kosmidis P.

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Source: Oncology. 2002; 63(4): 333-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12417787&dopt=Abstract ·

Down-regulation of COOH-terminal binding protein expression in malignant melanomas leads to induction of MIA expression. Author(s): Poser I, Golob M, Weidner M, Buettner R, Bosserhoff AK. Source: Cancer Research. 2002 October 15; 62(20): 5962-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12384563&dopt=Abstract

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Effect of the transcriptional repressor Mad1 on proliferation of human melanoma cells. Author(s): Ohta Y, Hamada Y, Saitoh N, Katsuoka K. Source: Experimental Dermatology. 2002 October; 11(5): 439-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12366697&dopt=Abstract

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Effects of C(2)-ceramide on the Malme-3M melanoma cell line. Author(s): Han W, Yoo J, Youn S, Kim D, Park K, Kim S, Kim K. Source: Journal of Dermatological Science. 2002 October; 30(1): 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12354415&dopt=Abstract

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Effects of FK317, a novel anti-cancer agent, on survival of mice bearing B16BL6 melanoma and Lewis lung carcinoma. Author(s): Inami M, Kawamura I, Tsujimoto S, Nishigaki F, Matsumoto S, Naoe Y, Sasakawa Y, Matsuo M, Manda T, Goto T. Source: Cancer Letters. 2002 July 8; 181(1): 39-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12430177&dopt=Abstract

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Efficient transduction and long-term retroviral expression of the melanoma-associated tumor antigen tyrosinase in CD34(+) cord bloodderived dendritic cells. Author(s): Temme A, Morgenroth A, Schmitz M, Weigle B, Rohayem J, Lindemann D, Fussel M, Ehninger G, Rieber EP. Source: Gene Therapy. 2002 November; 9(22): 1551-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12407427&dopt=Abstract

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Endothelin-1 decreases basic apoptotic rates in human melanoma cell lines. Author(s): Eberle J, Fecker LF, Orfanos CE, Geilen CC. Source: The Journal of Investigative Dermatology. 2002 September; 119(3): 549-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12230494&dopt=Abstract

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Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell-tumor cell fusion. Author(s): Linardakis E, Bateman A, Phan V, Ahmed A, Gough M, Olivier K, Kennedy R, Errington F, Harrington KJ, Melcher A, Vile R. Source: Cancer Research. 2002 October 1; 62(19): 5495-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12359759&dopt=Abstract

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Epithelioid malignant schwannoma of the superficial soft tissues vs. metastatic amelanotic melanoma. Author(s): Yamamoto T. Source: Journal of Cutaneous Pathology. 2002 October; 29(9): 569. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12358816&dopt=Abstract

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Estimation of macrophage IL-10 and NO secretion in the cytotoxicity against transplantable melanomas in relation to the progression of these tumours. Author(s): Kozlowska K, Cichorek M, Zarzeczna M. Source: Folia Morphol (Warsz). 2002; 61(3): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12416926&dopt=Abstract

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European approach to antibody-based immunotherapy of melanoma. Author(s): Altomonte M, Maio M. Source: Seminars in Oncology. 2002 October; 29(5): 471-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12407512&dopt=Abstract

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Excision margins in the treatment of primary cutaneous melanoma: a systematic review of randomized controlled trials comparing narrow vs

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wide excision. Author(s): Lens MB, Dawes M, Goodacre T, Bishop JA. Source: Archives of Surgery (Chicago, Ill. : 1960). 2002 October; 137(10): 1101-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12361412&dopt=Abstract ·

Expression of 12-lipoxygenase as a biomarker for melanoma carcinogenesis. Author(s): Winer I, Normolle DP, Shureiqi I, Sondak VK, Johnson T, Su L, Brenner DE. Source: Melanoma Research. 2002 September; 12(5): 429-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12394183&dopt=Abstract

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Expression of c-myc and bcl-2 in primary and advanced cutaneous melanoma. Author(s): Utikal J, Leiter U, Udart M, Kaskel P, Peter RU, Krahn GM. Source: Cancer Investigation. 2002; 20(7-8): 914-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12449722&dopt=Abstract

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Expression of melanocyte differentiation antigens and ki-67 in nodal nevi and comparison of ki-67 expression with metastatic melanoma. Author(s): Lohmann CM, Iversen K, Jungbluth AA, Berwick M, Busam KJ. Source: The American Journal of Surgical Pathology. 2002 October; 26(10): 1351-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12360050&dopt=Abstract

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Expression of melanoma antigen gene by cells from inflamed joints in juvenile rheumatoid arthritis. Author(s): McCurdy DK, Tai LQ, Imfeld KL, Schwartz M, Zaldivar F, Berman MA. Source: J Rheumatol. 2002 October; 29(10): 2219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12375337&dopt=Abstract

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Expression of multiple molecular phenotypes by aggressive melanoma tumor cells: role in vasculogenic mimicry.

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Author(s): Seftor EA, Meltzer PS, Schatteman GC, Gruman LM, Hess AR, Kirschmann DA, Seftor RE, Hendrix MJ. Source: Critical Reviews in Oncology/Hematology. 2002 October; 44(1): 17-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12398997&dopt=Abstract ·

Expression of p16 in sporadic primary uveal melanoma. Author(s): Lamperska K, Mackiewicz K, Kaczmarek A, Kwiatkowska E, Starzycka M, Romanowska B, Heizman J, Stachura J, Mackiewicz A. Source: Acta Biochimica Polonica. 2002; 49(2): 377-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12362979&dopt=Abstract

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Ferruginous foreign body: a clinical simulant of melanoma with distinctive histologic features. Author(s): Paproski SM, Smith SL, Crawford RI. Source: The American Journal of Dermatopathology. 2002 October; 24(5): 396-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12357199&dopt=Abstract

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Focus on melanoma. Author(s): Houghton AN, Polsky D. Source: Cancer Cell. 2002 October; 2(4): 275-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12398891&dopt=Abstract

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Frequency of nonsentinel lymph node metastasis in melanoma. Author(s): Shaw HM, Thompson JF. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2002 November; 9(9): 934; Discussion 934-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12417520&dopt=Abstract

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Functional polymorphism in EGF gene and malignant melanoma. Author(s): Rees J. Source: Lancet. 2002 August 17; 360(9332): 570. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12241682&dopt=Abstract

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Gene transfer of secreted-type modified interleukin-18 gene to B16F10 melanoma cells suppresses in vivo tumor growth through inhibition of tumor vessel formation. Author(s): Nagai H, Hara I, Horikawa T, Oka M, Kamidono S, Ichihashi M. Source: The Journal of Investigative Dermatology. 2002 September; 119(3): 541-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12230493&dopt=Abstract

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Gene-based therapy of malignant melanoma. Author(s): Schadendorf D. Source: Seminars in Oncology. 2002 October; 29(5): 503-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12407515&dopt=Abstract

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Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas. Author(s): Bastian BC, Xiong J, Frieden IJ, Williams ML, Chou P, Busam K, Pinkel D, LeBoit PE. Source: American Journal of Pathology. 2002 October; 161(4): 1163-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12368190&dopt=Abstract

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Genetic testing for melanoma. Author(s): Kefford R, Bishop JN, Tucker M, Bressac-de Paillerets B, Bianchi-Scarra G, Bergman W, Goldstein A, Puig S, Mackie R, Elder D, Hansson J, Hayward N, Hogg D, Olsson H. Source: The Lancet Oncology. 2002 November; 3(11): 653-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12424065&dopt=Abstract

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High-dose interferon and the U.K. guidelines for cutaneous melanoma. Author(s): Russell-Jones R, Healy C, Calonje E, Doherty M, Acland K. Source: The British Journal of Dermatology. 2002 October; 147(4): 832-4; Discussion 834-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12366454&dopt=Abstract

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Human melanocortin 1 receptor (MC1R) gene variants alter melanoma cell growth and adhesion to extracellular matrix. Author(s): Robinson SJ, Healy E. Source: Oncogene. 2002 November 14; 21(52): 8037-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12439754&dopt=Abstract

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Human melanoma cell migration along capillary-like structures in vitro: a new dynamic model for studying extravascular migratory metastasis. Author(s): Lugassy C, Kleinman HK, Fernandez PM, Patierno SR, Webber MM, Ghanem G, Spatz A, Barnhill RL. Source: The Journal of Investigative Dermatology. 2002 September; 119(3): 703-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12230517&dopt=Abstract

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Human melanomas of fibroblast and epithelial morphology differ widely in their ability to synthesize retinyl esters. Author(s): Simmons DP, Andreola F, De Luca LM. Source: Carcinogenesis. 2002 November; 23(11): 1821-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12419830&dopt=Abstract

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Identical T-cell receptor transcripts in multiple melanoma metastases. Author(s): Schrama D, Fuchs E, Brocker EB, Thor Straten P, Becker JC. Source: Cancer Research. 2002 October 15; 62(20): 5664-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12384521&dopt=Abstract

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Identification of the human PHLDA1/TDAG51 gene: down-regulation in metastatic melanoma contributes to apoptosis resistance and growth deregulation. Author(s): Neef R, Kuske MA, Prols E, Johnson JP. Source: Cancer Research. 2002 October 15; 62(20): 5920-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12384558&dopt=Abstract

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Imaging studies in patients with malignant melanoma in the female genital tract. Author(s): Takehara M, Saito T, Mizumoto H, Baba T, Tanaka R, Fujimoto T, Adachi K, Kudo R.

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Source: International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. 2002 September-October; 12(5): 506-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12366671&dopt=Abstract ·

Immunization by particle-mediated transfer of the granulocytemacrophage colony-stimulating factor gene into autologous tumor cells in melanoma or sarcoma patients: report of a phase I/IB study. Author(s): Mahvi DM, Shi FS, Yang NS, Weber S, Hank J, Albertini M, Schiller J, Schalch H, Larson M, Pharo L, Gan J, Heisey D, Warner T, Sondel PM. Source: Human Gene Therapy. 2002 September 20; 13(14): 1711-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12396624&dopt=Abstract

Vocabulary Builder Aberrant: Wandering or deviating from the usual or normal course. [EU] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Antiproliferative: Counteracting a process of proliferation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Apoptosis: A normal series of events in a cell that leads to its death. [NIH] Aspiration: Removal of fluid from a lump, often a cyst, with a needle and a syringe. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH]

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Autopsy: Postmortem examination of the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Bleomycin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU]

Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Cysteinyldopa: Found in large amounts in the plasma and urine of patients with malignant melanoma. It is therefore used in the diagnosis of melanoma and for the detection of postoperative metastases. Cysteinyldopa is believed to be formed by the rapid enzymatic hydrolysis of 5-S-glutathionedopa found in melanin-producing cells. [NIH] Cytokines: A class of substances that are produced by cells of the immune system and can affect the immune response. Cytokines can also be produced in the laboratory by recombinant DNA technology and given to people to affect immune responses. [NIH] Cytotoxic: Cell-killing. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external

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(exogenous) production. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Fenretinide: A drug being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH]

Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Groin: The area where the thigh meets the abdomen. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels

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despite adequate perfusion of the tissue by blood. [EU] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppression: Suppression of the body's immune system and its ability to fight infections or disease. Immunosuppression may be deliberately induced with drugs, as in preparation for bone marrow or other organ transplantation to prevent rejection of the donor tissue. It may also result from certain diseases such as AIDS or lymphoma or from anticancer drugs. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Interferons: Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Ipsilateral: Having to do with the same side of the body. [NIH] Keratoacanthoma: A benign (noncancerous), rapidly growing skin tumor that usually occurs on sun-exposed areas of the skin and that can go away without treatment. [NIH] Lethal: Deadly, fatal. [EU] Lipid: Fat. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form

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hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5-lipoxygenase, arachidonate 12lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Lomustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Lymphoscintigraphy: A method used to identify the sentinel node (the first draining lymph node near a tumor). A radioactive substance that can be taken up by lymph nodes is injected at the site of the tumor, and a doctor follows the movement of this substance on a computer screen. Once the lymph nodes that have taken up the substance are identified, they can be removed and examined to see if they contain tumor cells. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Membrane: A very thin layer of tissue that covers a surface. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monocyte: A type of white blood cell. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mutagenesis:

Process of generating genetic mutations. It may occur

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spontaneously or be induced by mutagens. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonmetastatic: Cancer that has not spread from the primary (original) site to other sites in the body. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Particle: A tiny mass of material. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH]

Pruritus: 1. itching; an unpleasant cutaneous sensation that provokes the desire to rub or scratch the skin to obtain relief. 2. any of various conditions marked by itching, the specific site or type being indicated by a modifying term. [EU] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Pulmonary: Relating to the lungs. [NIH]

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Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Radium: Radium. A radioactive element of the alkaline earth series of metals. It has the atomic symbol Ra, atomic number 88, and atomic weight 226. Radium is the product of the disintegration of uranium and is present in pitchblende and all ores containing uranium. It is used clinically as a source of beta and gamma-rays in radiotherapy, particularly brachytherapy. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Rheumatoid: Resembling rheumatism. [EU] Schwannoma: A tumor of the peripheral nervous system that begins in the nerve sheath (protective covering). It is almost always benign, but rare malignant schwannomas have been reported. [NIH] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Subcutaneous: Beneath the skin. [NIH] Tamoxifen: An anticancer drug that belongs to the family of drugs called antiestrogens. Tamoxifen blocks the effects of the hormone estrogen in the body. It is used to prevent or delay the return of breast cancer or to control its spread. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Tolerance: 1. the ability to endure unusually large doses of a drug or toxin. 2. acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

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Tretinoin: A drug that belongs to the family of drugs called retinoids. It is used in the treatment of acne and is being studied in cancer prevention. [NIH] Tumour: 1. swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. a new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Vaccinia: The cutaneous and sometimes systemic reactions associated with vaccination with smallpox vaccine. [EU] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH]

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CHAPTER 5. PATENTS ON MELANOMA Overview You can learn about innovations relating to melanoma by reading recent patents and patent applications. Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.28 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available to patients with melanoma within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available to patients with melanoma. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information.

28Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Patents on Melanoma By performing a patent search focusing on melanoma, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on melanoma: ·

Detection of loss of heterozygosity in tumor and serum of melanoma patients Inventor(s): Hoon; Dave S. B. (Los Angeles, CA) Assignee(s): John Wayne Cancer Institute (Santa Monica, CA) Patent Number: 6,465,177 Date filed: October 26, 1998 Abstract: A method is provided for assessing allelic losses on specific chromosomal regions in melanoma patents. The method relies on the evidence that free DNA may be released in the plasma/serum of cancer patients allowing the detection of DNA with LOH in the plasma/serum of cancer patients by analysis for microsatellite markers. The amount of and specific allelic loss allows a prognosis to be made regarding tumor diagnosis and progression, tumor metastasis, tumor recurrence, and mortality. Excerpt(s): The present invention is related to the fields of molecular biology and oncology and provides methods for diagnosis, staging and monitoring of melanoma patients. ... Recent developments in cancer therapeutics have demonstrated the need for more sensitive staging and monitoring procedures to ensure initiation of appropriate treatment, to define the end points of therapy and to develop and evaluate novel treatment modalities and strategies. In the management of melanoma patients, the choice of appropriate initial treatment depends on accurate assessment of the stage of the disease. Patients with limited or regional disease generally have a better prognosis and are treated differently than patients who have distant metastases (Minna, 1989). However, conventional techniques to detect these metastases are not very sensitive, and these patients are often not cured by primary tumor resection because they have metastases that are not identified by standard methods

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during preoperative staging. Thus, more sensitive methods to detect metastases in other types of carcinomas would identify patients who will not be cured by local therapeutic measures, for whom effective systemic therapies would be more appropriate. ... Thus, an efficient method of testing DNA microsatellite loci for LOH allows early diagnosis of melanoma patients and monitoring of the progression of the disease as well as effectiveness of the therapeutic regimen. Web site: http://www.delphion.com/details?pn=US06465177__ ·

Use of a melanoma differentiation associated gene (mda-7) for inducing apoptosis of a tumor cell Inventor(s): Fisher; Paul B. (Scarsdale, NY) Assignee(s): The Trustees of Columbia University in the City of New York (New York, NY) Patent Number: 6,355,622 Date filed: February 16, 1999 Abstract: This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid having the melanoma differentiation associated gene (mda-7) into the cell under conditions that permit the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of a cancer cell by introducing the gene product of the above-described gene into the cancerous cell so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a pharmaceutical composition having an amount of a nucleic acid having the melanoma differentiation associated gene (mda-7) or the gene product of a melanoma differentiation associated gene (mda-7) effective to reverse the cancerous phenotype of a cancer cell and a pharmaceutically acceptable carrier. Excerpt(s): Cancer is a complex multifactor and multistep process involving the coordinated expression and suppression of genes functioning as positive and negative regulators of oncogenesis (1-5). Direct cloning strategies, based on transfer of a dominant transforming or tumorigenic phenotype, have identified positive acting oncogenes (6-9). In contrast, the detection and cloning of genes that suppress the cancer phenotype have proven more difficult and elusive (10-15). A direct approach for isolating genes directly involved in regulating growth and differentiation involves subtraction hybridization between cDNA libraries constructed from actively growing cancer cells and cDNA libraries from cancer cells induced to lose proliferative capacity

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irreversibly and terminally differentiate (13,14). This experimental strategy has been applied to human melanoma cells, induced to terminally differentiate by treatment with recombinant human interferon .beta. (IFN-.beta.) and mezerein (MEZ), resulting in the cloning of novel melanoma differentiation-associated (mda) genes not previously described in DNA data bases (13,14). A direct role for specific mda genes in mediating growth and cell cycle control is apparent by the identification and cloning of mda-6 (13-16), which is identical to the ubiquitous inhibitor of cyclin-dependent kinases p21 (17). The importance of p21 in growth control is well documented and this gene has been independently isolated, as WAF-1, CIP-1, and SDI-1, by a number of laboratories using different approaches (18-20). These studies indicate that specific genes associated with proliferative control are induced and may contribute to the processes of growth arrest and terminal differentiation in human cancer cells. ... The mda-7 gene was cloned from a differentiation inducer (IFN-.beta. plus MEZ)-treated human melanoma (H0-1) subtracted library (13,14). The full-length mda-7 cDNA is 1718 nucleotides, and the major open reading frame encodes a novel protein of 206 aa with an M.sub.r of 23.8 kDa (21). Previous studies indicate that mda-7 is induced as a function of growth arrest and induction of terminal differentiation in human melanoma cells (14,21). mda-7 expression also inversely correlates with melanoma progression-i.e., actively growing normal human melanocytes express more mda-7 than metastatic human melanoma cells (21). Moreover, mda-7 is growth inhibitory toward human melanoma cells in transient transfection assays and in stable transformed cells containing a dexamethasone (DEX)inducible mda-7 gene (21). These studies indicate that mda-7 may contribute to the physiology of human melanocytes and melanomas, and this gene has growth suppressive properties when overexpressed in human melanoma cells. ... This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid including a melanoma differentiation associated gene (mda7) into the cell under conditions permitting the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of cancer cell in a subject by introducing the above-described nucleic acid into the subject's cancerous cell. Web site: http://www.delphion.com/details?pn=US06355622__

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·

Melanoma antigenic peptides Inventor(s): Nicolette; Charles A. (Marlborough, MA) Assignee(s): Genzyme Corporation (Framingham, MA) Patent Number: 6,306,640 Date filed: February 11, 1999 Abstract: Thus, this invention provides novel, synthetic polypeptide vaccines against human melanoma and methods for making these vaccines. Polynucleotides encoding these polypeptides are further provided herein. These compositions are useful as melanoma caccinies and in adoptive immunotherapy. Excerpt(s): This invention relates to the field of human tumor vaccines and in particular, vaccine components useful against human melanoma. ... Using a technique known as Solid-PHase Epitope REcovery ("SPHERE") (described in WO 97/35035), synthetic gp 100 melanoma epitopes that are specifically recognized by tumor specific immune effector cells have been identified. Using SPHERE, a library of oligopeptides between 8 to 10 amino acids in length was made and screened for their specificity and ability to raise immune effector cells that specifically target and lyse melanoma cells. ... Thus, this invention provides novel, synthetic polypeptide vaccines against human melanoma and methods for making these vaccines. Polynucleotides encoding these polypeptides are further provided herein. Web site: http://www.delphion.com/details?pn=US06306640__

·

Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same Inventor(s): Pardoll; Drew M. (Brookeville, MD), Jaffee; Elizabeth (Lutherville, MD), Adler; Adam (Pikesville, MD), Topalian; Suzanne L. (Brookeville, MD), Rosenberg; Steven A. (Potomac, MD) Assignee(s): The Johns Hopkins Universtiy (Baltimore, MD), The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,187,306 Date filed: August 5, 1997 Abstract: The invention pertains to a method of treating or protecting against melanoma that comprises (a) obtaining a melanoma cell line that expresses one or more shared immunodominant melanoma antigens, (b) modifying the melanoma cell line to render it capable of producing an

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increased level of a cytokine relative to the unmodified cell line, and (c) administering the melanoma cell line to a mammalian host that has melanoma or is at risk for developing melanoma. Preferably the melanoma cell line is allogeneic and is not MHC-matched to the host. Excerpt(s): The present invention pertains to a method of treating or protecting against melanoma using as a vaccine one or more melanoma tumor cell lines that express multiple immunodominantshared melanoma antigens. In particular, the invention pertains to the method of using an allogeneic melanoma cell line as a vaccine. The present invention also relates to a melanoma cell line that expresses shared immunodominant melanoma antigens, and to a composition comprising cells of the melanoma cell line. ... Also relevant to the use of tumor vaccines, it has been confirmed that T cells are the critical mediator of systemic antitumor immunity induced by tumor vaccines (reviewed by Pardoll, Trends in Pharmacological Sciences, 14, 202-08 (1993)). Thus, the production of a universal tumor vaccine, i.e., a vaccine that is applicable to the majority of patients with a particular type of cancer, requires knowledge of the existence of shared immunodominant tumor antigens recognized by T cells. Currently, shared immunodominant tumor antigens recognized by T cells have been identified in only one human cancer, melanoma. Melanoma is a malignant neoplasm derived from cells that are capable of forming melanin, and may occur in the skin of any part of the body, in the eye, or, less commonly, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. Primary malignant melanoma of the skin is the leading cause of death from all diseases arising in the skin. Metastatic melanoma is frequently thought of as resistant to treatment. In fact, the most effective single agent for treatment of disseminated melanoma, dacarbazine (dimethyltriazenoimidazolecarboxamide or DTIC), induces a partial remission in only 20 percent of cases, and a complete response in less than 5 percent of cases (Fitzpatrick et al., "Malignant Melanoma of the Skin", In Harrison's Principles of Internal Medicine, Braunwald et al., eds., Eleventh Ed. (McGraw-Hill Book Company: NY, 1987) 1595-97)). ... The shared immunodominant melanoma antigens recognized by T cells fall into two main categories. One category of antigens encompasses proteins that are produced in melanoma cells, and are not produced in any other adult tissues with the exception of testis. These so-called tumor-specific shared antigens include the MAGE family antigens MAGE-1 and MAGE-3. Of these two antigens, MAGE-3 appears to be more widely produced and immunodominant than MAGE-1. MAGE-3 also is produced in other nonmelanotic tumors such as small cell lung cell carcinoma (SCLC), non-small cell lung cell carcinoma (non-SCLC),

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squamous cell carcinoma of the head and neck (SCCHN), colon cancer, and breast cancer. Similarly, MAGE-1 also is produced in breast cancer, glioblastoma, neuroblastoma, SCLC, and medullary cancer of the thyroid. The other category of shared melanoma antigens encompasses melanocyte lineage-specific differentiation antigens. These lineagespecific differentiation antigens are produced in melanocytes and their malignant counterpart, melanoma, and are produced in no other cells or tissues identified to date. These differentiation antigens include MART1/Melan-A, tyrosinase, GP75, and GP100. These melanoma antigens, as well as other antigens (e.g., recently identified tumor-specific mutated antigens that may or may not prove to be shared), are further described in Table 1. It also is likely that further shared immunodominant melanoma antigens will be identified. Web site: http://www.delphion.com/details?pn=US06187306__ ·

Method of determining melanoma micrometastasis using tyrosinase Inventor(s): Reintgen; Douglas S. (Tampa, FL) Assignee(s): University of South Florida (Tampa, FL) Patent Number: 6,153,388 Date filed: February 5, 1999 Abstract: A highly sensitive method to detect melanoma micrometastasis by examining lymph nodes for the presence of tyrosinase messenger RNA. In a preferred mode, this is accomplished using the combination of reverse transcription and double round polymerase chain reaction (RTPCR). The amplified samples are examined on a 2% agarose gel and tyrosinase is seen as a 207 base pair fragment. The lymph nodes examined are determined using pre- and intra- operative node mapping. Excerpt(s): Malignant melanoma is a form of skin cancer that can develop from melanocytes, cells that are capable of forming melanin, a darkbrown to black pigment. Most melanomas develop from a previous mole over a period of several months or years and occur most commonly in fair-skinned people that are intolerant to sunlight. There are several distinct types of melanomas. Prognosis depends on the kind of melanoma, its depth of invasion, its location, and the age and health of the patient. ... According to new statistics, malignant melanoma could become a lethal epidemic in the next decade. In 1993, 32,000 people in the United States developed melanoma, and 6,420 died from it. Exactly why the rate of skin cancer is growing so rapidly is not known although accumulating evidence suggests that sun exposure and the thinning ozone layer play a major role. ... Patients who receive early diagnosis and

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treatment have a high chance of survival. Most patients in the early stages of melanoma undergo surgery to remove the primary tumor. Patients with locally advanced or metastatic disease usually also undergo some type of chemotherapy and may also receive radiation therapy although radiation is not usually very effective against melanoma. Other treatments include cytotoxic drugs, treatment with immunological substances and autologous (self) bone marrow transplant to enhance the patient's immune system. Web site: http://www.delphion.com/details?pn=US06153388__ ·

Oligonucleotide treatments and compositions for human melanoma Inventor(s): Zupi; Gabriella (Rome, IT) Assignee(s): Istituto Regina Elena (Rome, IT) Patent Number: 6,080,727 Date filed: March 25, 1997 Abstract: The invention generally provides for compositions and methods of inhibiting the proliferation of human melanoma cancer cells. By administering a therapeutically effective amount of a c-myc oligonucleotide to a human melanoma cancer cell, melanoma cancer cell proliferation can be arrested or inhibited, metastases reduced from a tumor, and apoptosis induced in melanoma cancer cells. Oligonucleotides that are complementary to c-myc polynucleotides are referred to herein as "c-myc oligonucleotides." A particularly efficacious embodiment of the invention relates to compositions and methods concerning the co-administration of c-myc oligonucleotides and cisplatin. Excerpt(s): The present invention relates to compositions and methods for treating melanoma based on oligonucleotides complementary to cmyc polynucleotides and co-administration of such oligonucleotides with cisplatin. ... Melanoma tumors are a growing health concern to millions of people worldwide. Because the growth of tumors is influenced by many factors, including the activation of multiple oncogenes, such as protooncogenes, it has been difficult to ascertain the cellular mechanisms underlying cancer cell biology. Consequently, available therapies are limited in their ability to arrest tumor growth from human melanoma cancer cells. ... In the case of melanoma, the c-myc proto-oncogene is expressed in human melanoma cancer cells growing as tumors. The contribution of this proto-oncogene to the development of melanoma in humans has remained unelucidated until the present invention. For instance, it has been not understood, until the present invention, whether c-myc expression is necessary for melanoma cancer cell proliferation,

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whether c-myc expression plays a minor role in melanoma cancer cell proliferation or whether c-myc expression is a result of melanoma cancer cell proliferation rather than the cause the of melanoma cell proliferation. The role of c-myc expression in melanoma metastasis and apoptosis has been also not understood. Nor has the role of c-myc expression been established for the chemoresistance of melanoma to cisplatin. Web site: http://www.delphion.com/details?pn=US06080727__ ·

Detection of melanoma or breast metastasis with a multiple marker assay Inventor(s): Hoon; Dave S. B. (Los Angeles, CA), Conrad; Andrew J. (Los Angeles, CA), Schmid; Peter (Los Angeles, CA) Assignee(s): NGI/Cancer Tech Company, LLC (Los Angeles, CA) Patent Number: 6,057,105 Date filed: December 9, 1997 Abstract: Methods for detecting metastasis of melanoma and breast cancer cells, detecting subclinical metastasis, and monitoring treatment are disclosed. Kits for use in such methods also are disclosed. The methods provide for the detection of nucleic acids corresponding to multiple melanoma or breast cancer specific markers using template dependent amplification processes. Methods using multiple markers provide increased sensitivity over existing methods. Excerpt(s): The present invention relates generally to the field of cancer diagnostic techniques. In particular, the invention relates to the detection of genetic markers indicative of melanoma or breast cancer cells. In one example, detection of multiple markers is achieved by polymerase chain reaction assay. ... Cancers are one of the leading causes of disease, being responsible for 526,000 deaths in the United States each year (Boring et al., 1993). For example, breast cancer is the most common form of malignant disease among women in Western countries and, in the United States, is the most common cause of death among women between 40 and 55 years of age (Forrest, 1990). The incidence of breast cancer is increasing, especially in older women, but the cause of this increase is unknown. Malignant melanoma is another form of cancer whose incidence is increasing at a frightening rate, at least sixfold in the United States since 1945, and is the single most deadly of all skin diseases (Fitzpatrick, 1986). ... The recent development of the PCR assay (Mullis and Faloona, 1987; Erlich, 1989) for detection of occult metastatic tumor cells in blood using specific markers has provided a new approach to assess tumor progression (Smith et al., 1991; Naito et al., 1991). In one

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study, circulating melanoma cells in blood were detected by PCR analysis using the tyrosinase gene marker (Smith et al., 1991). Seven melanoma patients with metastatic disease were analyzed, but only four were positive. Other studies using PCR have been used to detect circulating tumor cells in melanoma, as well as in breast, prostate and neuroblastoma cancer patients (Smith et al., 1991; Datta et al., 1994; Moreno et al., 1992; Naito et al., 1991). These studies, employing a single marker, were limited by their ability to discriminate cancer cells from normal cells also carrying the marker, thus reducing specificity and reliability. In addition, tumor heterogeneity has caused sensitivity problems where a single, specific marker has been employed. Web site: http://www.delphion.com/details?pn=US06057105__ ·

Isolated nucleic acid molecules which encode a melanoma specific antigen and uses thereof Inventor(s): Pfreundschuh; Michael (Homburg/Saar, DE) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 6,025,191 Date filed: January 3, 1996 Abstract: The invention involves the isolation of a nucleic acid molecule which encodes a melanoma associated antigen. Cell lines and expression vectors which include this and related sequences, as well as uses of these molecules, are described. Excerpt(s): This invention relates to methodologies for identifying molecules of interest. In particularly preferred embodiments, the invention relates to the identification of molecules associated with pathological conditions such as cancer, (melanoma or renal cancer, e.g.), Hodgkin's Disease, autoimmune diseases and so forth. Also a part of the invention are the isolated molecules found as a result of the inventive method. These molecules include, inter alia, protein-containing molecules, isolated nucleic acid molecules encoding these, and antibodies which specifically bind to the protein-containing molecules. For convenience, the method described herein will be referred to as "serological fishing". ... The following disclosure describes a methodology referred to as serological fishing. In it, a cell sample is taken from a subject afflicted with a pathological condition. The cells preferably are exemplary of the pathology. For example, if the subject has melanoma, the cells are melanoma cells. If the subject is suffering from a neural disorder, e.g., then the cells are preferably a sample of the afflicted cells. This approach is warranted because the afflicted cells are most probably

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the best source of protein-containing molecules of interest, i.e., such molecules which are specifically associated with the pathological condition of interest. ... The protocols set forth in the preceding examples were followed, using biopsied tissue taken from different subjects suffering from (i) malignant melanoma, (ii) astrocytoma, and (iii) Hodgkin's Disease. Table 1, which follows, summarized the results, including those obtained with the renal cancer study, set out in detail in Examples 1-6, supra. Web site: http://www.delphion.com/details?pn=US06025191__ ·

Use of texaphyrins in detection of melanin and melanin metabolites diagnostic of melanotic melanoma Inventor(s): Woodburn; Kathryn W. (Sunnyvale, CA), Young; Stuart W. (Portola Valley, CA) Assignee(s): Pharmacyclics, Inc. (Sunnyvale, CA) Patent Number: 6,022,526 Date filed: July 30, 1997 Abstract: Melanotic melanoma tumor or cells, melanin, or melanin metabolites are detected, identified, and localized when bound to texaphyrins or texaphyrin metal complexes. The present invention provides texaphyrins and texaphyrin metal complexes as reagents for in vivo or in vitro detection for melanin or melanin metabolites predictive of the presence of melanotic melanoma. Excerpt(s): The present invention relates generally to the fields of cancer diagnosis, and particularly to methods for diagnosis of melanotic melanoma or metastatic melanotic melanoma. The use of texaphyrins for in vivo or in vitro detection of melanin or melanin metabolites diagnostic of melanotic melanoma is provided herein. A further aspect of the invention is a method of identifying, localizing, and diagnosing melanincontaining cells or tissues. ... The incidence and mortality rates of malignant melanoma continue to rise dramatically throughout the world. In the United States, it is estimated that one in 90 Americans will develop melanoma by the year 2000. Melanoma is one of the most feared neoplasms because of the high mortality associated with metastatic involvement. ... Malignant melanoma is commonly found in early stages in the form of a skin lesion. The lesion often results from the transformation of a preexisting nevus or discolored patch of skin containing aggregates of melanocytes. The best prognostic factor for determining the presence of metastatic disease is the depth of invasion of the primary lesion. Lesions with a depth greater than 0.8 mm have an

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increased risk for metastases. Melanomas usually metastasize first via the lymphatic system, with involvement of regional nodes, and then via blood vessels, with dissemination to subcutaneous tissue and to the liver, lungs, and brain. The presence of regional lymph node metastasis is predictive of a poor prognosis. Web site: http://www.delphion.com/details?pn=US06022526__ ·

Methods for screening for possibility or melanoma in a subject Inventor(s): Pfreundschuh; Michael (Homburg/Saar, DE) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 6,017,716 Date filed: October 28, 1997 Abstract: This invention involves screening for possibility of melanoma. The screening method relies on the binding of antibodies to protein encoded by a nucleic acid molecule defined by the nuclotide sequence of SEQ ID NO:2. Excerpt(s): This invention relates to methodologies for identifying molecules of interest. In particularly preferred embodiments, the invention relates to the identification of molecules associated with pathological conditions such as cancer, (melanoma or renal cancer, e.g.), Hodgkin's Disease, autoimmune diseases and so forth. Also a part of the invention are the isolated molecules found as a result of the inventive method. These molecules include, inter alia, protein-containing molecules, isolated nucleic acid molecules encoding these, and antibodies which specifically bind to the protein-containing molecules. For convenience, the method described herein will be referred to as "serological fishing". ... The following disclosure describes a methodology referred to as serological fishing. In it, a cell sample is taken from a subject afflicted with a pathological condition. The cells preferably are exemplary of the pathology. For example, if the subject has melanoma, the cells are melanoma cells. If the subject is suffering from a neural disorder, e.g., then the cells are preferably a sample of the afflicted cells. This approach is warranted because the afflicted cells are most probably the best source of protein-containing molecules of interest, i.e., such molecules which are specifically associated with the pathological condition of interest. ... The protocols set forth in the preceding examples were followed, using biopsied tissue taken from different subjects suffering from (i) malignant melanoma, (ii) astrocytoma, and (iii) Hodgkin's Disease. Table 1, which follows, summarized the results,

Patents 179

including those obtained with the renal cancer study, set out in detail in Examples 1-6, supra. Web site: http://www.delphion.com/details?pn=US06017716__ ·

Polynucleotides related to monoclonal antibody 1A7 and use for the treatment of melanoma and small cell carcinoma Inventor(s): Chatterjee; Malaya (Lexington, KY), Foon; Kenneth A. (Lexington, KY), Chatterjee; Sunil K. (Lexington, KY) Assignee(s): Board of Trustees of the University of Kentucky (Lexington, KY) Patent Number: 5,935,821 Date filed: November 21, 1996 Abstract: The present invention relates to monoclonal antibody 1A7. This is an anti-idiotype produced by immunizing with an antibody specific for ganglioside GD2, and identifying a hybridoma secreting antibody with immunogenic potential in a multi-step screening process. Also disclosed are polynucleotide and polypeptide derivatives based on 1A7, including single chain variable region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the 1A7 antibody overcomes immune tolerance and induces an immune response against GD2, which comprises a combination of anti-GD2 antibody and GD2-specific T cells. The invention further provides methods for treating a disease associated with altered GD2 expression, particularly melanoma, neuroblastoma, glioma, soft tissue sarcoma, and small cell carcinoma. Patients who are in remission as a result of traditional modes of cancer therapy may be treated with a composition of this invention in hopes of reducing the risk of recurrence. Excerpt(s): In particular, glycosphingolipid GD2 is expressed at high density by tumors of human neuroectodermal origin; including malignant melanoma, neuroblastoma, glioma, soft tissue sarcoma and small cell carcinoma of the lung. The GD2 antigen is absent in most normal tissues, except for low levels in brain and peripheral nerve. ... Melanoma is one of the human diseases for which there is an acute need of new therapeutic modalities. It is a particularly aggressive form of skin cancer, and occurs in increased frequency in individuals with regular unguarded sun exposure. In the early phases, melanoma is characterized by proliferation at the dermal-epidermal junction, which soon invades adjacent tissue and metastasizes widely. Worldwide, 70,000 patients are diagnosed and 25,000 deaths are reported each year. The American Cancer Society projects that by the year 2000, 1 out of every 75 Americans

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will be diagnosed with melanoma in their lifetime. ... Fortunately, melanoma is one of the cancers for which gangliosides hold significant promise as a target antigen (Livingston (1995) Immunol. Rev. 145:147166). Increased expression of GD2 has been observed in a majority of malignant melanoma cells. Several murine monoclonal anti-GD2 antibodies were reported to suppress the growth of tumors of neuroectodermal origin in athymic (nu/nu) mice or cause remission in patients with metastatic melanoma. A human-mouse chimeric anti-GD2 antibody remissions in patients with metastatic neuroblastoma. The mechanism is thought to involve antibody dependent cellular cytotoxicity (ADCC) or complement-mediated cytotoxicity (CMC). Clinical responses have been obtained by treating with monoclonal antibodies against GM2, GD2 and GD3. Active immunization with a ganglioside vaccine comprising GM2 produced anti-GM2 antibodies in 50/58 patients, who survived longer on average than antibody negative patients. Web site: http://www.delphion.com/details?pn=US05935821__ ·

Polyvalent melanoma vaccine Inventor(s): Morton; Donald L. (24752 Malibu Rd., Malibu, CA 90265) Assignee(s): none reported Patent Number: 5,882,654 Date filed: October 14, 1992 Abstract: A new polyvalent melanoma cell vaccine is disclosed comprised of one or more allogeneic melanoma cell lines which contain effective concentrations of melanoma associated antigens. Further disclosed are a method of stimulating an immunological response by administering the described vaccine as well as a method of prognosticating a patient. Excerpt(s): This invention relates to polyvalent melanoma cell vaccines comprised of allogeneic melanoma cell lines which contain high concentrations of antigens which are immunogenic in melanoma patients. ... Early attempts to induce tumor regression in cancer patients by immunizing them with their own tumors or with those from other patients were not properly evaluated; they lacked suitable controls and immunologic studies to determine whether the patients had actually been successfully immunized. However, there are well-documented instances of vaccine-induced immunity against cancer in animal models and evidence for serologic and clinical responses in man to suggest that active specific immunotherapy can be developed as a modality of treatment for cancer. Active immunotherapy became a realistic strategy after it was

Patents 181

demonstrated that the induction of DCH reactions in certain malignant neoplasms, such as those induced by the intralesional injection of BCG (an attenuated strain of Mycobacterium) resulted in the regression and eradication of the directly injected cutaneous melanoma metastases and occasionally also in the regression of uninjected metastases. These reports rekindled interest in the century-old concept of a vaccine for cancer and revived efforts to find the crucial formulas for effective vaccine therapy. ... Research efforts during the past twenty-five years have been primarily directed towards the development of more effective methods for the active specific immunotherapy of melanoma. Ann. Surg., pp 463-482 (October 1992), incorporated herein by reference. The conceptual basis for this focus has been based upon the original observation that the intratumoral injection of cutaneous metastases in melanoma patients with bacillus Calmette-Guerin (BCG) resulted in systemic enhancement of active immunity, producing rising titers of anti-melanoma antibodies and regression of other uninjected metastatic cutaneous lesions. See Morton et al., Surgery 1968; 64:233-240; Morton et al., Surgery 1970; 68:158-164. Biopsy of uninjected melanoma lesions that showed clinical regression demonstrated intense lymphocytic infiltration. Web site: http://www.delphion.com/details?pn=US05882654__ ·

Antiidiotypic antibodies associated antigen

for

high

molecular

weight-melanoma

Inventor(s): Hardman; Norman (Riehen, CH), Pluschke; Gerd (Merzhausen, DE), Murray; Brendan (Nelkenring, CH) Assignee(s): Novartis Corporation (Summit, NJ) Patent Number: 5,866,124 Date filed: May 22, 1996 Abstract: The invention concerns antiidiotypic antibodies comprising human constant regions, and murine variable regions bearing the internal image of human high molecular weight-melanoma associated antigen which have the specificity of said antibody. These antiidiotypic monoclonal antibodies have immune-regulatory functions and can therefore be used for diagnostic and therapeutic purposes, such as the treatment of melanoma. Excerpt(s): The invention concerns antiidiotypic monoclonal antibodies comprising human constant regions, and variable regions bearing the internal image of human high molecular weight-melanoma associated antigen (HMW-MAA), and derivatives of said antibodies. The antibodies of the invention and their derivatives are useful for diagnostic,

182 Melanoma

prophylactic and therapeutic purposes, such as the immune therapy of melanoma. ... Melanomas are tumors of the skin, less frequently of mucous membranes, some of which are benign. Malignant melanomas are carcinomas of neuroectodermal origin generally derived from melanocytes (pigment-producing cells), sometimes from mucous membranes, the chorioid coat or the meninges. There are several types of malignant melanoma which differ in localization, way of spreading and production of metastases. ... Conventional treatment of melanoma includes surgery, radio- or chemotherapy, and the application of biological response modifiers. However, these methods have proved to be insufficient to combat the illness, e.g. to prevent tumor recurrence, and are complicated by a large number of severe side effects. Therefore, it is desirable to develop therapeutic approaches which overcome these drawbacks and can replace or be used in combination with conventional treatment. Web site: http://www.delphion.com/details?pn=US05866124__ ·

P15 and tyrosinase melanoma antigens and their use in diagnostic and therapeutic methods Inventor(s): Robbins; Paul F. (Silver Spring, MD), Rosenberg; Steven A. (Potomac, MD) Assignee(s): The United States of America as represented by the Secretary, Department (Washington, DC) Patent Number: 5,843,648 Date filed: January 10, 1995 Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated p15. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the p15 melanoma antigen and a second melanoma antigen designated tyrosinase. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma. Excerpt(s): This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to the p15 gene which encodes melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative, diagnostic and therapeutic applications which employ these genes, proteins or peptides. This invention also relates to preventative, diagnostic or therapeutic

Patents 183

applications utilizing tyrosinase peptides which encode melanoma antigens. ... Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells ("Cellular and Molecular Immunology" (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S.; W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women ("Cellular and Molecular Immunology" (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S.; W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993) Principles and Practice of Oncoloqy 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Principles and Practice of Oncoloqy 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy have emerged as new and promising methods for treating melanoma. ... T cells play an important role in tumor regression in most murine tumor models. Tumor infiltrating lymphocytes (TIL) that recognize unique cancer antigens can be isolated from many murine tumors. The adoptive transfer of these TIL plus interleukin-2 can mediate the regression of established lung and liver metastases (Rosenberg, S. A., et al., (1986) Science 233:1318-1321). In addition, the secretion of IFN.gamma. by injected TIL significantly correlates with in vivo regression of murine tumors suggesting activation of T-cells by the tumor antigens. (Barth, R. J., et al., (1991) J. Exo. Med. 173:647-658). The known ability of tumor TIL to mediate the regression of metastatic cancer in 35 to 40% of melanoma patients when adoptively transferred into patients with metastatic melanoma attests to the clinical importance of the antigens recognized (Rosenberg, S. A., et al., (1988) N Enql J Med 319:1676-1680; Rosenberg S. A. (1992) J. Clin. Oncol. 10:180-199). Web site: http://www.delphion.com/details?pn=US05843648__

Patent Applications on Melanoma As of December 2000, U.S. patent applications are open to public viewing.29 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years). The following patent applications have been filed since December 2000 relating to melanoma: 29

This has been a common practice outside the United States prior to December 2000.

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·

Methods for inhibition of tumorigenic properties of melanoma cells Inventor(s): Herlyn, Meenhard; Kapaettu ; (Swarthmore, PA)

(Wynnewood, PA), Satyamoorthy,

Correspondence: Licata & Tyrrell P.C.; 66 E. Main Street; Marlton; NJ; 08053; US Patent Application Number: 20020165188 Date filed: January 30, 2002 Abstract: The present invention provides a method for preventing proliferation of melanoma cells by contacting melanoma cells with an agent which is capable of modulating the expression of E-cadherin in the melanoma cells thereby restoring keratinocyte control over melanoma cell proliferation. Excerpt(s): Melanoma is a relatively common cancer. The incidence of cutaneous melanoma has risen rapidly in the last several decades (Parker et al., 1997, C A Cancer J. Clin 47:5-27; Ries et al., 2000, Cancer, 88:2398424). Melanoma is notorious for its propensity to metastasize and its poor response to current therapeutic regimens. The transition from benign lesions to invasive, metastatic cancer occurs through a complex process involving changes in expression and function of oncogenes or tumor suppressor genes (Meier et al., 1998, Am. J. Pathol. 156:193-200). ... In the human epidermis, melanocytes residing at the basement membrane are interspersed among basal keratinocytes. E-cadherin is physiologically expressed on the cell surface of keratinocytes and melanocytes, and is the major adhesion molecule (Hsu et al., 1996, J. Investig. Dermatol. Symp. Proc. 1:188-94; Tang et al., 1994, J. Cell Sci. 107:983-92). A progressive loss of E-cadherin expression occurs during melanoma development (Danen et al., 1996, Melanoma Res., 6:127-31; Hsu et al., 1996, J. Investig. Dermatolo Symp. Proc. 1:188-94; Scott & Cassidy, J. Invest Dermatol., 1998, 111:243-50; Silye et al., 1998, J. Pathol. 186:350-55). Under natural conditions, melanocytes express E-cadherin on their surface but melanoma cells do not (Hsu et al., 1994, J. Invest. Dermatol. Symp. Proc. 1:188-194). Additionally, melanoma cells express N-cadherin, while melanocytes do not. Melanoma cells express greater amounts of MelCAM and .alpha..sub.v.beta..sub.3 than do melanocytes. However, both cell types express .alpha.-catenin, .beta.-catenin and plakoglobin (Ozawa et al., J. Cell Biol., 1992, 116:989-996; Knudsen et al., 1995, J. Cell Biol. 130:67-77). Growth, proliferation, dendricity and cell-surface molecule composition of melanocytes are normally under the control of basal layer-type keratinocytes (Herlyn et al., 1987, Cancer Res. 47:3057-3061; Valyi-Nagy et al., 1993, Lab. Invest 69:152-159,; Shih et al., Am. J. Of Pathol., 1994, 145:837-845). Melanoma cells are refractory to the

Patents 185

regulatory controls normally exerted by keratinocytes and therefore proliferate in an uncontrolled manner. Isolated and cultured melanocytes lose their normal phenotype, but regain it upon co-culture with basal layer type keratinocytes. The homeostatic effects of basal layer-type keratinocytes exert these effects upon melanocytes. ... Increased proliferation of human melanocytes in vitro by HGF has previously been reported (Halaban et al., 1992, Oncogene 7:2195-206; Imokawa et al., 1998, Biochem J. 330:1235-9; Matsumoto et al., 1991, Biochem Biophys Res Commun 176:45-51), however, the mitogenic activity became obvious only when HGF acted together with other growth factors such as bFGF (Halaban et al., 1992, Exs, 65:329-39). It has been previously shown that cMet is co-localized with .beta.-catenin and E-cadherin at regions of cell to cell contact in human colon and breast cancer cell lines (Hiscox and Jiang, 1999, Biochem Biophys Res Commun.,261:406-11 ; Kamei et al., 1999, Oncogene 18:6776-84). Previous studies have shown a progressive loss of E-cadherin expression during melanoma development (Hsu et al.,1996, J. Investigat. Dermatol. Symp. Proc.; Johnson, 1999, Cancer Metastasis Rev.18:345-57). Physiologically, HGF is secreted by cells of mesenchymal origin and acts as mitogen, motogen and morphogen for many epithelial cells (Gherardi et al., 1989 Proc. Natl. Acad. Sci. USA, 86:5844-8; Nakamura et al., 1989 Nature 342:440-3; Stoker et al., 1987, Nature, 327:239-42) and is therefore considered a paracrine factor. Until the present invention it was previously unknown how c-Met is activated or the source of its ligand, HGF. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compositions for treatment of melanoma and method of using same Inventor(s): Houghton, Alan N. ; (New York, NY), Bergman, Philip J. ; (Tarrytown, NY), Wolchok, Jedd D. ; (New York, NY) Correspondence: Oppedahl and Larson LLP; P O Box 5068; Dillon; CO; 80435-5068; US Patent Application Number: 20020150589 Date filed: November 27, 2001 Abstract: Melanoma can be treated in a mammalian subject by administering to the subject an immunologically-effective amount of a xenogeneic melanoma-associated differentiation antigen. For example, genetic immunization with a plasmid containing a sequence encoding human gp75 has been shown to be effective in treatment of dogs with melanoma.

186 Melanoma

Excerpt(s): This application relates to compositions for treatment of melanoma and to a method of using such compositions. The invention utilizes compositions containing xenogeneic differentiation antigens which are associated with melanoma to provide effective therapy. ... Differentiation antigens are tissue-specific antigens that are shared by autologous and some allogeneic tumors of similar derivation, and on normal tissue counterparts at the same stage of differentiation. Differentiation antigens have been shown to be expressed by a variety of tumor types, including melanoma, leukemia, lymphomas, colorectal carcinoma, breast carcinoma, prostate carcinoma, ovarian carcinoma, pancreas carcinomas, and lung cancers. For example, differentiation antigens expressed by melanoma cells include Melan-A/MART-1, Pmel17, tyrosinase, and gp75. Differentiation antigen expressed by lymphomas and leukemia include CD19 and CD20/CD20 B lymphocyte differentiation markers). An example of a differentiation antigen expressed by colorectal carcinoma, breast carcinoma, pancreas carcinoma, prostate carcinoma, ovarian carcinoma, and lung carcinoma is the mucin polypeptide muc-1. A differentiation antigen expressed by breast carcinoma is her2/neu. The her2/neu differentiation antigen is also expressed by ovarian carcinoma. Differentiation antigens expressed by prostate carcinoma include prostate specific antigen, prostatic acid phosphatase, and prostate specific membrane antigen. ... Melanocyte differentiation antigens have been shown to be recognized by autoantibodies and T cells of persons with melanoma, and to be relevant autoantigens. Wang et al., J. Exp. Med. 183: 799-804 (1996); Vijayasaradhi et al., J. Exp. Med. 171: 1375-1380 (1990). Unfortunately, in most cases, the immune system of the individual is tolerant of these antigens, and fails to mount an effective immune response. For the treatment of cancers where the tumor expresses differentiation antigens therefore, it would be desirable to have a method for stimulating an immune response against the differentiation antigen in vivo. It an object of the present invention to provide such a method. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 187

·

Nucleic acid molecule associated with prostate cancer and melanoma immunodetection and immunotherapy Inventor(s): Vielkind, Juergen R. ; (Vancouver, CA) Correspondence: Leopold Presser, Esq.; Scully, Scott, Murphy & Presser; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20020146702 Date filed: May 11, 2001 Abstract: The present invention relates to the use of isolated nucleic acid molecules associated with prostate cancer and melanoma and compositions derived therefrom. The present invention further relates to methods for diagnosing and treating prostate cancer and melanoma and other related pathological conditions by employing such nucleic acid molecules and compositions. Excerpt(s): The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrkreceptor tyrosine kinase for the diagnosis and therapy of melanoma and prostate cancer. This invention also relates to the use of isolated nucleic acid molecules associated with prostate cancer and melanoma for diagnosing and treating pathological conditions including prostate cancer and melanoma. ... Human malignant melanoma arises from a series of stages starting with the harmless mole, going through intermediate stages of radial to invasive growth and ending in the destructive final stage of metastatic melanoma. Melanoma usually resists chemotherapy as well as radiotherapy. Surgery is the most effective treatment. However, for it to be effective, surgery requires early diagnosis which is unfortunately hampered by the lack of accurate markers for melanoma. Melanoma associated antigens have been found, but they are of little diagnostic value. For example, the nerve growth factor receptor is found in high density on melanoma cells. However, monoclonal anti-nerve growth receptor antibodies are specific for neural crest cell diseases rather than for melanoma alone. Likewise, other melanoma associated antigens against which antibodies have been raised are nonspecific for melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells. Examples are the monoclonal antibodies raised against in vitro grown melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells. ... Frequent routine rectal examinations are the best means of demonstrating early and operable prostatic tumors. Measurement of prostate specific antigen (PSA) as a screening test for prostate cancer has been used but presents

188 Melanoma

both technical difficulties and a high false positive rate. Prostatic acid phosphatase also has been used as a marker for prostate cancer but does not detect all cancers. The most successful detection of prostate cancer is from the combined use of a digital rectal exam, transrectal ultrasound and detection of prostate specific antigen. The sensitivities of the three tests individually vary from 50% to 85% but the positive predictive value fluctuates around 30%. When these three investigations are summated, the detection rate is approximately twice as high as when a single parameter is used. The only reliable procedure for definitive diagnosis of prostatic carcinoma is by open perineal biopsy. Needle biopsies and cytologic studies of prostatic fluid are unreliable for the diagnosis of early cancer but are useful methods of obtaining a histological diagnosis in the more advanced cases. It therefore is of interest to identify in particular, early stage prostatic cancer and to identify non-invasive methods of treating prostatic cancer. It also is of interest to identify a melanomaassociated antigen which is specific for melanoma as compared to normal melanocytes as well as other normal and malignant cells. An antibody raised against such an antigen can be used in the diagnosis and treatment of melanoma. The antibody itself or an immunotoxin may find use as an antiproliferative agent. According to the present invention a gene has now been shown to be implicated in the genesis of prostate carcinoma. The gene is identified as KIAA0909 is useful for detecting and treating pathological conditions such as prostate cancer and melanoma in humans. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Method for Treating Melanoma Inventor(s): Hirschman, Shalom Z. ; (Riverdale, NY) Correspondence: Myron Cohen; Cohen Pontani Lieberman & Pavane; 551 Fifth Avenue Suite 1210; New York; NY; 10176 Patent Application Number: 20020107184 Date filed: November 4, 1997 Abstract: The present invention discloses a method for treating patients having melanoma or melanoma associated symptoms by parenterally administering Product R, a peptide-nucleic acid preparation. Excerpt(s): The present invention relates to a method for using Product R as hereinafter defined to treat patients having melanoma. ... Human melanoma, a malignant melanocytic tumor arising in a pigmented area: skin, mucous membranes, eyes, and CNS, represents the principal cause of death in patients with skin cancer in the United States and Europe.

Patents 189

Malignant melanomas vary in size, shape, and color and in their propensity to invade and metastasize. About 40 to 50% of malignant melanomas develop from pigmented moles. Malignant transformation of pigmented moles may result from changes in size or color, especially spread of red, white, and blue pigmentation to surrounding normal skin; changes in surface characteristics, consistency or shape; or signs of inflammation in surrounding skin. ... Melanoma includes four major types: lentigo-maligna melanoma which appears on the face or other sunexposed areas in elderly patients as an asymptomatic, large, flat, tan or brown macule with darker brown or black spots scattered irregularly on its surface; superficial spreading melanoma which is usually asymptomatic and occurs most commonly on women's legs and men's torsos as a plaque with raised, indurated edges, and often shows red, white, and blue spots or small, sometimes protuberant, blue-black nodules; nodular melanoma which may occur anywhere on the body and is seen as dark, protuberant papules or a plaque that varies in color from pearl to gray to black; acroletiginous melanoma which is uncommon and arises on palmar, plantar, and subungual skin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Novel protein related to melanoma-inhibiting protein and uses thereof Inventor(s): Pan, Yang ; (Bellevue, WA), Barnes, Thomas M. ; (Brookline, MA) Correspondence: Jean M. Silveri; Millennium Pharmaceuticals, INC.; 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20020103360 Date filed: February 16, 2001 Abstract: Novel TANGO 130 nucleic acid molecules which encode proteins having homology to melanoma-inhibiting protein are disclosed. In addition to TANGO 130 nucleic acid molecules and proteins, the invention further provides isolated TANGO 130 fusion proteins, antigenic peptides and anti-TANGO 130 antibodies. The invention also provides vectors containing nucleic acid molecules of the invention, host cells into which the vectors have been introduced and non-human transgenic animals in which a TANGO 130 gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided. Excerpt(s): A variety of factors participate in the tightly controlled regulation of cell growth and differentiation. One molecule believed to be involved in such regulation is Melanoma-Inhibiting Protein (MIA).

190 Melanoma

Human and murine MIA cDNAs were first cloned from malignant melanoma cells and shown to inhibit growth of melanoma cells in vitro (Blesch et al. (1994) Cancer Res. 54:5695). Human MIA cDNA encodes a 24 amino acid signal peptide and a mature 107 amino acid secreted protein, and shares little or no homology with other known proteins. ... Cancer cells and embryonic cells are growth inhibited after treatment with MIA, observed as cell cycle arrest accompanied by a rounded up cell morphology and decreased adherence to the substrate. Furthermore, MIA expression is enhanced in developing cartilage and in chondrosarcoma (Bosserhoff et al. (1997) Dev. Dyn. 208:516). Based on this data, a biological role for MIA in embryonic cell growth and morphogenesis has been suggested, and a therapeutic application of MIA in the development of an antitumor therapeutic has been proposed. Additionally, MIA expression correlates with progressive malignancy of melanocytic lesions (Bosserhoff et al. (1997) J. Biol. Chem. 271:490), and MIA protein levels are enhanced in serum of patients with malignant melanoma (Bosserhoff et al. (1997) Cancer Res. 57:3149), supporting another proposed use of MIA as a marker of cancer progression. ... MIA and its bovine orthologue, CD-RAP, participate in activities involving cellular proliferation. These molecules inhibit the growth of melanocytes and chondrosarcoma tumor cells, and therefore have therapeutic utility in the treatment of malignant melanoma and chondrosarcoma. Additionally, they are abundantly expressed in malignant melanoma and are useful as serum markers of metastatic melanoma. Thus, molecules related to MIA and CD-RAP, e.g., TANGO 130 molecules, can be used to treat patients with such metastatic tumors. Also, TANGO 130 molecules of the invention which are overexpressed in abnormal cells can be used as serum markers in the diagnosis and monitoring of associated disease states. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Use of a melanoma differentiation associated gene (mda 7) for reversing a cancerous phenotype Inventor(s): Fisher, Paul B. ; (Scarsdale, NY) Correspondence: Baker Botts L.L.P.; 44th Floor; 30 Rockefeller Plaza; New York; NY; 10112-0228; US Patent Application Number: 20020091098 Date filed: November 21, 2001 Abstract: This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid having the

Patents 191

melanoma differentiation associated gene (mda-7) into the cell under conditions that permit the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of a cancer cell by introducing the gene product of the above-described gene into the cancerous cell so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a pharmaceutical composition having the melanoma differentiation associated gene (mda-7) or the gene product of the melanoma differentiation associated gene (mda-7) effective to reverse the cancerous phenotype of a cancer cell and a pharmaceutically acceptable carrier. Excerpt(s): Cancer is a complex multifactor and multistep process involving the coordinated expression and suppression of genes functioning as positive and negative regulators of oncogenesis (1-5). Direct cloning strategies, based on transfer of a dominant transforming or tumorigenic phenotype, have identified positive acting oncogenes (6-9). In contrast, the detection and cloning of genes that suppress the cancer phenotype have proven more difficult and elusive (10-15). A direct approach for isolating genes directly involved in regulating growth and differentiation involves subtraction hybridization between cDNA libraries constructed from actively growing cancer cells and cDNA libraries from cancer cells induced to lose proliferative capacity irreversibly and terminally differentiate (13, 14). This experimental strategy has been applied to human melanoma cells, induced to terminally differentiate by treatment with recombinant human interferon .beta. (IFN-9) and mezerein (MEZ), resulting in the cloning of novel melanoma differentiation-associa- ted (mda) genes not previously S described in DNA data bases (13, 14). A direct role for specific mda genes in mediating growth and cell cycle control is apparent by the identification and cloning of mda-6 (13-16), which is identical to the ubiquitous inhibitor of cyclin-dependent kinases p21 (17). The importance of p21 in growth control is well documented and this gene has been independently isolated, as WAF-1, CIP-1, and SDI-1, by a number of laboratories using different approaches (18-20). These studies indicate that specific genes associated with proliferative control are induced and may contribute to the processes of growth arrest and terminal differentiation in human cancer cells. ... The mda-7 gene was cloned from a differentiation inducer (IFN-.beta. plus MEZ)-treated human melanoma (H0-1) subtracted library (13, 14). The full-length mda7 cDNA is 1718 nucleotides, and the major open reading frame encodes a novel protein of 206 aa with an M.sub.r of 23.8 kDa (21). Previous studies indicate that mda-7 is induced as a function of growth arrest and induction of terminal differentiation in human melanoma cells (14,21).

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mda-7 expression also inversely correlates with melanoma progression-i.e., actively growing normal human melanocytes express more mda-7 than metastatic human melanoma cells (21). Moreover, mda-7 is growth inhibitory toward human melanoma cells in transient transfection assays and in stable transformed cells containing a dexamethasone (DEX)inducible mda-7 gene (21). These studies indicate that mda-7 may contribute to the physiology of human melanocytes and melanomas, and this gene has growth suppressive properties when overexpressed in human melanoma cells. ... This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid including a melanoma differentiation associated gene (mda7) into the cell under conditions permitting the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of cancer cell in a subject by introducing the above-described nucleic acid into the subject's cancerous cell. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Melanoma and prostate cancer immunodetection and immunotherapy

specific

antibodies

for

Inventor(s): Vielkind, Juergen R. ; (Vancouver, CA) Correspondence: Scully, Scott, Murphy & Presser; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20020055121 Date filed: April 19, 2001 Abstract: Methods and compositions are provided for detecting antigens having a specific epitope associated with melanoma and prostatic carcinoma. The epitope is present in melanoma cells and prostatic cancer cells but is essentially absent from melanocytes and normal prostatic tissue. The antibody can be used in diagnostic methods for histochemical detection of human melanoma and prostate carcinoma, of various progression stages and in treatment of melanoma and prostate carcinoma. Excerpt(s): The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrkreceptor tyrosine kinase for the diagnosis and therapy of melanoma and prostate cancer. ... Human malignant melanoma arises from a series of stages starting with the harmless mole, going through intermediate stages of radial to invasive growth and ending in the destructive final stage of metastatic melanoma. Melanoma usually resists chemotherapy as

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well as radiotherapy. Surgery is the most effective treatment. However, for it to be effective, surgery requires early diagnosis which is unfortunately hampered by the lack of accurate markers for melanoma. Melanoma associated antigens have been found, but they are of little diagnostic value. For example, the nerve growth factor receptor is found in high density on melanoma cells. However, monoclonal anti-nerve growth receptor antibodies are specific for neural crest cell diseases rather than for melanoma alone. Likewise, other melanoma associated antigens against which antibodies have been raised are nonspecific for melanoma cells. Examples are the monoclonal antibodies raised against in vitro grown melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells. ... Frequent routine rectal examinations are the best means of demonstrating early and operable prostatic tumors. Measurement of prostate specific antigen as a screening test for prostate cancer has been used but presents both technical difficulties and a high false positive rate. Prostatic acid phosphatase also has been used as a marker for prostate cancer but does not detect all cancers. The most successful detection of prostate cancer is from the combined use of a digital rectal exam, transrectal ultrasound and detection of prostate specific antigen. The sensitivities of the three tests individually vary from 50% to 85% but the positive predictive value fluctuates around 30%. When these three investigations are summated, the detection rate is approximately twice as high as when a single parameter is used. The only reliable procedure for definitive diagnosis of prostatic carcinoma is by open perineal biopsy. Needle biopsies and cytologic studies of prostatic fluid are unreliable for the diagnosis of early cancer but are useful methods of obtaining a histological diagnosis in the more advanced cases. It therefore is of interest to identify in particular, early stage prostatic cancer and to identify non-invasive methods of treating prostatic cancer. It also is of interest to identify a melanoma-associated antigen which is specific for melanoma as compared to normal melanocytes as well as other normal and malignant cells. An antibody raised against such an antigen can be used in the diagnosis and treatment of melanoma. The antibody itself or an immunotoxin may find use as an antiproliferative agent. So far no single gene has been shown to be implicated in the genesis of prostate carcinoma. Once such genes are identified and characterized this will provide important insight into the development of this disease. In a larger frame work, it may then be possible to identify individuals at high risk and to predict whether or not an indolent tumor has the potential to become malignant. This may lead to new avenues for treatment of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Inhibition of mitogen-activated protein kinase (MAPK) pathway: a selective therapeutic strategy against melanoma Inventor(s): Koo, Han-Mo ; (Kentwood, MI), Vande Woude, George F. ; (Ada, MI) Correspondence: Venable, Baetjer, Howard and Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20020054869 Date filed: August 31, 2001 Abstract: Inhibitors of the MAPK pathway, including MEK-directed proteases and small molecule inhibitors, are cytotoxic to human melanoma cells in vitro and in vivo via apoptotic mechanisms. These compounds are used to kill melanoma cells and to treat subjects with melanoma, either alone or in combination with other therapeutic modalities. Excerpt(s): The invention in the field of biochemistry and medicine relates to methods to kill melanoma cells and treat melanoma tumors in a selective manner using compositions that inhibit the mitogen-activated protein kinase (MAPK) pathway. ... The present inventors and their colleagues observed in the National Cancer Institute's Antineoplastic Drug Screen (NCI-ADS) database (Koo, H. -M. et al., Canc Res 56:52115216 (1996); Monks, A. et al. J Natl Cane Inst 83:757-766 (1991); Grever, M. R. et al., Sem Oncol 19:622-638 (1992)) that the lethal factor (LF) of Bacillus anthracis, a MEK-directed protease (Duesbery, N. S. et al., Science 280:734-737 (1998); Vitale, G. et al., Biochem Biophys Res Comm 248:706-711 (1998)) and the small molecule pharmacological MEK inhibitor PD98059 (Dudley, D. T. et al., Proc Nat'l Acad Sci USA 92:76867689 (1995); Alessi, D. R. et al., J Biol Chem 270:27489-27494 (1995)) displayed enhanced growth inhibition specifically against melanoma lines among the many different tumor cell lines tested. Another small molecule MEK inhibitor, PD184352, has been described (Sebolt-Leopold, J. S. et al., Nature Med. 5: 810-816 (1999)). ... The present invention is based on subsequent work wherein the inventors explored the mechanism by which inhibition of the MAPK signaling would selectively inhibit the growth of the human melanoma cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Paclitaxel treatment regimen for metastatic melanoma Inventor(s): Helson, Larry ; (Quakertown, PA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20020013362 Date filed: April 18, 2001 Abstract: The invention relates generally to a method of using paclitaxel in a specific Q4D.times.3 schedule and dosage for patients with malignant melanoma. The low risk-benefit ratio of this specific schedule provides a method for therapeutic use for all stages of severity of disease ranging from local resectable tumor to diagnosed widespread malignant melanoma. Excerpt(s): The present invention broadly concerns a treatment regimen for patients with local or disseminated malignant melanoma. More specifically, the present invention relates to a paclitaxel treatment schedule and dosages which are different from the standard drug schedule of once every 21 days. ... Melanoma was once a rarity in oncological management. An exponential increase in incidence during the past 25 years has made it an important focus for treatment-related research. In 1995 there were an estimated 34,000 new cases and 7,000 deaths. (Wingo, Pa. 1995.) Treatment options and the effectiveness of systemic chemotherapy for advanced melanoma are limited, rendering it a fatal disease. Most agents and combinations of agents are no better than the single agent dacarbazine. (Legha 1990.) The results of scheduling for dacarbazine are quite variable depending upon the number of sequential days of treatment. Evidence is available that suggests that longer treatment schedules are more effective than shorter in producing overall response rates. (Nathanson, L. 1971; McClay E. F. and McClay, M. E., 1996.) These observations may be reflecting the pharmacodynamic characteristics of dacarbazine, particularly its dwell time in the cell and the duration of its biological effects. Based on this same premise, the pharmacodynamics of any drug considered for treatment of this disease must be taken into consideration, and in effect dictates the strategy for its schedule of administration. ... Disseminated melanoma, however, is an example of a malignancy which has exhibited an apparent low response rate and constitutive drug resistance to paclitaxel. For example, using a 24-hour infusion of paclitaxel at 250 mg/M.sup.2 once every three weeks, partial responses in 3/25 patients with melanoma were reported (Legha S. S., 1990). A majority of the melanoma patients could not tolerate greater than 200 mg/M.sup.2 paclitaxel (Legha 1990). Another phase II study, using the same schedule in 28 patients, resulted in five objective

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responses (Einzig, A. I., 1988). Since December 1992, a single dose of 130 mg/m.sup.2 every 21 days has been the accepted norm. Data generated in other laboratories and clinical trials have failed to demonstrate more effective schedules and dosages for the treatment of melanoma (McClay, E. F. and McClay, M. E., 1996). Therefore, a current need exists for alternative schedules and dosages for the treatment of melanoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Melanoma therapy Inventor(s): Rybak, Mary Ellen ; (Waren, NJ), Rose, Esther Helen ; (Westfield, NJ) Correspondence: Schering-Plough Corporation; Patent Department (K-61, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20010038833 Date filed: July 12, 2001 Abstract: Methods for treating treatment-naive as well as treatmentexperienced patients having melanoma to increase the progression-free survival time involving administering a therapeutically effective amount of pegylated interferon-alpha, e.g., preferably pegylated interferon alpha2b, as adjuvant therapy to definitive surgery are disclosed. Excerpt(s): This invention relates to an improved therapy for treating patients having melanoma after definitive surgical removal of the lesions by administering a therapeutically effective dose of pegylated interferonalpha for a time sufficient to increase progression-free survival time. ... Melanoma incidence is increasing at a rate that exceeds all that for other solid tumors. Patients with primary melanoma of greater than 4 mm or metastatic melanoma involving regional lymph nodes possess a 50 to 90% mortality risk following surgical excision of the primary melanomas. ... Recently, the Eastern Cooperative Oncology Group ("ECOG") published results of the use of interferon alpha-2b in patients with stage III cutaneous melanoma as adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma (Kirkwood, J. M., et al. J. Clin. Oncol., Vol 14: (1996) pages 4-17.) The interferon alpha-2b therapy used by ECOG involved an induction phase of 20 million IU of interferon alpha-2b per square meter of body surface area (m.sup.2) administered intravenously ("IV") daily for five days every week for four weeks followed by maintenance interferon alpha therapy of 10 million IU/m.sup.2 administered subcutaneously ("SC") three times a week ("TIW") for 48 weeks. A significant improvement in median disease-free survival and overall survival were observed versus control (observation)

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despite dosage reductions or delays for toxicity in 50% of the patients during the IV induction therapy phase and in 48% of the patients in the SC maintenance phase. Hematologic, neurologic and constitutional toxicities occurred among these patients requiring dose reduction or withdrawal from the interferon alpha therapy. Subject compliance with the dosage and dosage regimen during both phases is considered to be important to achieve maximum clinical benefit. Accordingly, there is a need for improved therapy for treating patients having melanoma with higher patient compliance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with melanoma, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “melanoma” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on melanoma. You can also use this procedure to view pending patent applications concerning melanoma. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, starshaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH]

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Bacillus: A genus of bacteria of the family Bacillaceae, including large aerobic or facultatively anaerobic, spore-forming, rod-shaped cells, the great majority of which are gram-positive and motile. The genus is separated into 48 species, of which three are pathogenic, or potentially pathogenic, and the remainder are saprophytic soil forms. Many organisms historically called Bacillus are now classified in other genera. [EU] CNS: Central nervous system. The brain and spinal cord. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Constitutional: 1. affecting the whole constitution of the body; not local. 2. pertaining to the constitution. [EU] Dexamethasone: A synthetic steroid (similar to steroid hormones produced naturally in the adrenal gland). Dexamethasone is used to treat leukemia and lymphoma and may be used to treat some of the problems caused by other cancers and their treatment. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Glioblastoma: A general term that refers to malignant astrocytoma, a type of brain tumor. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [NIH] Inflammation: A response of redness, swelling, pain, and a feeling of heat in certain areas which is meant to protect tissues affected by injury or disease. [NIH]

Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH]

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Metabolite: process. [EU]

Any substance produced by metabolism or by a metabolic

Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH] Mycobacterium: An organism of the genus Mycobacterium. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Oligopeptides: Peptides composed of between two and twelve amino acids. [NIH]

Paclitaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH] Pancreas: A glandular organ located in the abdomen. It makes pancreatic juices, which contain enzymes that aid in digestion, and it produces several hormones, including insulin. The pancreas is surrounded by the stomach, intestines, and other organs. [NIH] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Perineal: Pertaining to the perineum. [EU] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyvalent: Having more than one valence. [EU] Preoperative: Preceding an operation. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Radiotherapy: The treatment of disease by ionizing radiation. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer

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have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Stimulant: 1. producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. an agent or remedy that produces stimulation. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Substrate: A substance upon which an enzyme acts. [EU] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Trustees: Board members of an institution or organization who are entrusted with the administering of funds and the directing of policy. [NIH] Withdrawal: 1. a pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) a substancespecific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU]

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CHAPTER 6. BOOKS ON MELANOMA Overview This chapter provides bibliographic book references relating to melanoma. You have many options to locate books on melanoma. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on melanoma include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “melanoma” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on melanoma:

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What You Really Need To Know About Moles and Melanoma Source: Baltimore, MD: The Johns Hopkins University Press. 2000. 232 p. Contact: Available from Johns Hopkins University Press. Hopkins Fulfillment Service, P.O. Box 50370, Baltimore, MD 21211-4370. (410) 5166956. Fax (410) 516-6998. E-mail: [email protected]. Website: www.jhupbooks.com. Price: $14.95 plus shipping and handling. ISBN 0801863945. Summary: This book provides people who have melanoma with the most up to date information on the prevention, diagnosis, and treatment of this form of skin cancer. Part one focuses on the recognition and prevention of melanoma. Topics include the structure of the skin; the features of nonmelanoma skin cancers; the characteristics of pigmented lesions such as freckles, seborrheic keratoses, lentigos, and nevi; and the causes and warning signs of melanoma. One chapter focuses on the risk factors for melanoma, including number of moles; changing, atypical, and congenital moles; intense, intermittent sun exposure; prior severe sunburns; melanoma in a close relative; personal history of melanoma; skin type; hair color; age; gender; immune system suppression; prior psoralen and ultraviolet A treatments to the skin; xeroderma pigmentosa; and atypical mole syndrome. Other topics include prevention and early detection of melanoma and education about skin cancer and melanoma. Part two deals with the diagnosis and treatment of melanoma. Chapters discuss removing and treating the primary lesion; determining the stage of the cancer; evaluating and treating regional lymph nodes at the time of diagnosis; and using adjuvant therapy such as immunotherapy, radiation therapy, chemotherapy, vitamins and diet therapy, and lifestyle changes. Other topics include treating melanoma that has metastasized with drugs, surgery, and experimental therapies and managing pain and the end of life. Answers to frequently asked questions about diagnosing and treating melanoma are listed. Part three focuses on unusual noncutaneous and less common forms of cutaneous melanoma and reviews melanoma research. The book contains color photographs and line drawings, a glossary, and a guide to resources such as support and advocacy organizations and websites for people who have melanoma. 11 figures, 2 tables, and 13 color plates.

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Melanoma Prevention, Detection, and Treatment Source: New Haven, CT, Yale University Press, 140 p., 1998. Contact: Yale University Press, New Haven, CT. Internet/Email: www.yale.edu/yup/.

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Summary: Melanoma Prevention, Detection, and Treatment is a guide that examines all aspects of malignant melanoma, but with an emphasis on providing practical information that can save lives by detecting the malignancy early. The book contains eight chapters: (1) Close Encounters with Melanoma; (2) What Is Melanoma?; (3) Who Gets Melanoma and Why; (4) Finding Early Melanoma; (5) If You Have Melanoma; (6) When Melanoma Metastasizes; (7) Tending to Your Spirits; and (8) Future Promise: Prevention of Melanoma. The book also contains two appendices that (1) describe the staging system for melanoma; and (2) present a list of resources for melanoma, including lists of computerized databases, addresses of helpful organizations and support groups, and lists of additional publications. ·

Melanoma: Diagnosis and Treatment Source: New Orleans, LA, Louisiana Cancer Consortium, 62 p., 1994. Contact: Louisiana Cancer Consortium, 1430 Tulane Avenue, New Orleans, LA 70112. (504) 588-5518. Summary: Melanoma: Diagnosis and Treatment contains information for physicians about educating their patients and the public about methods of prevention, diagnosis, and treatment for various types of melanoma. Chapters, written by various physicians, contain figures (including color photographs of various melanomas), tables, and references. Contents include (1) introduction (the problem of melanoma, melanoma variants, and implications for the physician); (2) epidemiology of melanoma (incidence, mortality, and survival); (3) risk factors and risk management; (4) evaluation of nevi and guidelines for patient monitoring; (5) diagnosis of melanoma (patient history, physical examination, major growth patterns of melanoma, differential diagnosis, and biopsies); (6) treatment of the melanoma patient (clinical management of malignant melanoma, surgical excision, node dissection, adjunctive therapy, management of advanced of metastatic melanoma, and immune therapy of melanoma); (7) melanoma in dark-skinned people (palms, soles, and mucous membranes); (8) prevention of malignant melanoma (excessive sunlight, early detection, and routine skin self-examination); (9) patient education (sources of pamphlets on melanoma); and (10) public awareness efforts (Skin Cancer and Melanoma Detection Month).

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Primary and Secondary Prevention of Malignant Melanoma Source: New York, NY, Karger, Pigment Cell, Volume 11, 130 p., 1996. Contact: S. Karger AG, 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479; (860) 675-7834.

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Summary: Primary and Secondary Prevention of Malignant Melanoma contains articles by world authorities in the fields of primary and secondary prevention of malignant melanoma. The incidence of Malignant melanoma continues to increase steadily, while mortality is also increasing in almost all parts of the world, although the rate of mortality increase is less rapid than that of the morbidity due to earlier detection and treatment of lesions. Primary prevention campaigns are currently aimed at encouraging sensible sun exposure, which is defined as preventing visible sunburn and reducing sun exposure around noon when the ultraviolet light intensity is at its greatest. Secondary prevention efforts devote time and energy to campaigns aimed at earlier diagnosis and prompt treatment. Chapters include (1) Methodological Issues in Research on Primary and Secondary Prevention of Malignant Melanoma, (2) Secondary Prevention of Malignant Melanoma in Europe, (3) Secondary Prevention of Skin Cancer in Australia, (4) Primary Prevention Activities for Malignant Melanoma in the United States, (5) Primary Prevention Activities in the United Kingdom, (6) Programs for the Primary Prevention of Melanoma in Australia, and (7) Evaluation of Programs to Modify Sun Exposure. Secondary prevention efforts may have an effect in 3-5 years, but primary prevention campaigns may not have an effect for 20-30 years. Those persons embarking on primary and secondary prevention of skin cancer campaigns must therefore be extremely careful to put in place good audit measures that will exist for years or even decades.

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “melanoma” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:30 In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of

30

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Biology of melanomas, by Myron Gordon [et al. Author: Conference on the Biology of Normal and Atypical Pigment Cell Growth (1st: 1946: New York); Year: 1948; New York] 1948.

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Current cancer research on preclinical and clinical studies on diagnosis, prognosis, therapy, and immunology of melanomas and other skin cancers. Author: [prepared for the ICRDB Program by the Current Cancer Research Project Analysis Center]; Year: 1979; [Bethesda, Md.]: U. S. Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health, National Cancer Institute; Springfield, Va.: [available from] National Technical Information Service, 1979.

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Enhancement of natural resistance to malignant melanoma with special reference to the beneficial effects of concurrent infections and bacterial toxin therapy. Author: Fowler, George A., 1914-; Year: 1969; New York, 1969.

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Human malignant melanoma. Author: edited by Wallace H. Clark, Jr., Leonard I. Goldman, and Michael J. Mastrangelo; Year: 1979; New York: Grune ; Stratton, c1979. ; ISBN: 0808911104 http://www.amazon.com/exec/obidos/ASIN/0808911104/icongroupin terna

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Malignant melanoma: clinical and histological diagnosis. Author: Vincent J. McGovern; Year: 1976; New York: Wiley, c1976. ; ISBN: 0471584177 http://www.amazon.com/exec/obidos/ASIN/0471584177/icongroupin terna

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Malignant melanoma of the skin and mucous membrane. Author: G. W. Milton; with chapters by V. J. McGovern, Martin G. Lewis; Year: 1977; Edinburgh; New York: Churchill Livingstone; New York: distributed in U. S. by Longman, 1977. ; ISBN: 0443014221 http://www.amazon.com/exec/obidos/ASIN/0443014221/icongroupin terna

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Melanoma [by] C. O. Knutson, J. M. Hori [and] J. S. Spratt, Jr. Author: Knutson, Carl O., 1938-; Year: 1971; Chicago, Year Book Medical Publishers, 1971. ; ISBN: 0815199031 http://www.amazon.com/exec/obidos/ASIN/0815199031/icongroupin terna

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Melanoma and skin cancer; proceedings. [Editor: W. H. McCarthy]. Author: International Cancer Conference (1972: Sydney); Year: 1972; Sydney, Blight [1972]

information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Melanoma of the skin, with special reference to histological differential diagnosis, clinical picture, and end results of treatment. [Tr. by Eva Palmgren]. Author: Brandt, Gunnar; Year: 1956; Helsingfors, 1956.

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Melanoma. Author: Tygart, Robert Lewis, 1926-; Year: 1955; Des Moines, 1955.

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Melanotic tumors of the skin [by] Herbert Z. Lund and Jane Merrill Kraus. Author: Lund, Herbert Z., 1907-; Year: 1962; [Washington] Armed Forces Institute of Pathology [1962]

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Melanotic tumors; biology, pathology and clinical features, by Joseph N. Attie and René A. Khafif. Author: Attie, Joseph Nathan, 1918-; Year: 1964; Springfield, Ill., Thomas [c1964]

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Nature of melanoma, by Vincent K. McGovern and Malcolm M. Lane Brown. Author: McGovern, Vincent J; Year: 1969; Springfield, Ill., Thomas [c1969]

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Pigmented nevi, juvenile melanomas and malignant melanomas in children. Author: McWhorter, Henry Etten, 1921-; Year: 1954; [Minneapolis] 1954.

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Primary malignant melanoma of the upper respiratory tract and oral cavity. Author: Brown, Warren Franklin, 1931-; Year: 1962; [Minneapolis] 1962.

Chapters on Melanoma Frequently, melanoma will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with melanoma, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and melanoma using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and typing in “melanoma” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on melanoma:

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Chapter 92: Neoplasms: Cutaneous Melanoma Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 1080-1116. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 7593749 or (614) 759-3641. E-mail: [email protected]. Price: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on cutaneous melanoma. The incidence of potentially lethal melanocyte malignancy has been increasing steadily in the past several decades. Risk factors for cutaneous melanoma include exposure to solar radiation; phenotypic features such as light skin pigmentation, ease of sunburning, blond or red hair, pale or light skin, prominent tendency toward freckling, and blue or green eyes; reaction of the skin to sunlight; occupation and social status; family history of melanoma; presence of clinically atypical nevi; history of prior melanoma; and gender and hormonal factors. Stages of tumor progression in the melanocytic system that have been suggested include benign melanocytic nevi, melanocytic nevi with architectural and cytologic atypia, primary malignant melanoma in radial and vertical growth phases, and metastatic malignant melanoma. Tumorigenesis of melanoma must take into account various clinical observations, including the association between nevi and melanoma in at least 30 percent of cases, the role of sunlight in the pathogenesis of melanoma, pigmentary phenotype of patients in whom melanoma develops, and family history of melanoma and other genetic factors. The major growth patterns of melanoma are lentigo maligna, superficial spreading, nodular, and acral lentiginous. Other melanoma variants are melanoma of the mucosa and desmoplastic neurotropic melanoma. The article presents the clinical characteristics and histopathology of these types of melanoma, discusses clinical detection and histologic diagnosis, presents a staging system, and describes clinical and histopathologic parameters of possible prognostic significance. In addition, the article provides guidelines on evaluating suspected or newly diagnosed melanoma, reviews advances in the management of primary melanoma and regional and distant metastases, and presents suggestions on prevention and early detection. Other topics include melanoma arising in congenital nevi, melanoma and pregnancy, melanoma in childhood and adolescence, metastatic and recurrent melanoma, and metastatic melanoma with no known primary site. 22 figures, 11 tables, and 261 references.

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Melanoma of the Skin Source: in Pennsylvania Cancer Incidence and Mortality: 1994-1998. Harrisburg, PA, Pennsylvania Department of Health, pp. 92-99, June 2001. Contact: Pennsylvania Department of Health, Bureau of Health Statistics, 555 Walnut Street, 6th Floor, Harrisburg, PA 17101. (717) 783-2548. Internet/Email: www.health.state.pa.us/stats/. Summary: Melanoma of the Skin, a chapter in Pennsylvania Cancer Incidence and Mortality, 1994-1998, presents skin melanoma incidence and mortality data for Pennsylvania (PA) residents from 1989 through 1998, stratified by race, sex, and county. From 1994 through 1998, average annual age-adjusted incidence rates for melanoma of the skin among white males and females were 15.0 and 9.5 cases per 100,000, respectively, much higher than among black males and females, 0.7 case/100,000. There were 2,149 cases of cutaneous melanoma diagnosed in 1998 among PA residents. This represents the largest number of cases reported during the period 1989 through 1998 and is an increase of nearly 90 percent from the number of cases (1,132) reported in 1989. Annual age-adjusted melanoma incidence rates for white males and females have been increasing, a situation paralleled by data for the United States as a whole. The average annual age-adjusted melanoma mortality rates for 1994 through 1998 were much higher for whites, especially males. There were 402 deaths from skin melanoma among PA residents in 1998, the highest annual number recorded from 1989 through 1998. There were no discernible trends in the annual age-adjusted death rates for white males and females from 1989 through 1998. Nearly 91 percent of melanoma cases reported in 1998 were diagnosed during the in situ and local stages of disease. The chapter also summarizes risk factors and American Cancer Society recommendations for the early detection of skin melanoma.

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Melanoma Skin Cancer Source: in Run the Good Race: Cancer Prevention and Control in Missouri. Jefferson City, MO, Missouri Department of Health, Bureau of Cancer Control, pp. 20-21, 2000. Contact: Missouri Department of Health, Bureau of Cancer Control, P.O. Box 570, Jefferson City, MO 65102-0570. (800) 316-0935. Summary: Melanoma Skin Cancer, a chapter in Run the Good Race: Cancer Prevention and Control in Missouri, indicates that Missouri ranks 21st highest in the United States for melanoma skin cancer deaths. The main risk factors include (1) exposure to the ultraviolet radiation in

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sunlight; (2) use of tanning beds and sun lamps, even as little as 1 to 3 times a year; (3) working with exposure to certain chemicals, such as vinyl chloride and PCB's; and (4) being genetically predisposed with fair or red hair, blue eyes, and pale complexion. Those most at risk for this disease include blond or red-headed white women age 65 or older. Those more likely to die are white men over the age of 65 years. Whites are nine times more likely to die from melanoma than African Americans. The death rate for men is twice that of women. Persons over age 65 years are two times as likely to die from melanoma as people age 45 to 64 years, and eight times more likely to die than people under age 45 years. ·

Melanoma Source: in Cancer Screening: Theory and Practice. Kramer, B.S.; Gohagan, J.K.; Prorok, P.C.; eds. Marcel Dekker, Inc., New York, NY, pp. 379-408, 1999. Contact: Marcel Dekker, Inc., 270 Madison Avenue, New York, NY 10016. (212) 696-9000. FAX: (212) 685-4540. Internet: http://www.dekker.com. Summary: Melanoma, a chapter in Cancer Screening: Theory and Practice, focuses on issues related to melanoma screening. Melanoma incidence and death rates have been increasing in most industrialized nations. Many researchers consider melanoma screening a concept that deserves scientific attention, but not all clinical aspects of melanoma are conducive to screening. Some melanomas may be clinically unrecognizable. The detectable preclinical phase in some melanomas may be absent or of too short a duration for detection by periodic screening. Screening often finds nonmelanoma skin cancers. Screening can introduce biases or uncover the thin nonspreading form of melanoma. Persons with melanoma or other forms of skin cancer may be (1) unaware of a lesion; (2) aware of a lesion, but not suspicious that it is cancer; (3) aware and suspicious of a lesion, but not concerned enough to have it checked; or (4) aware and suspicious of a lesion, but with real or perceived barriers to having it checked. The optimal melanoma screening study design is a prospective randomized trial showing sustained reductions in melanoma mortality rates in a defined population, but this type of study may not be practical. Case-control studies can offer initial data to evaluate screening programs. Most published studies on melanoma screening are descriptive studies. These studies should be interpreted with caution. The authors reviewed the status of descriptive studies involving high-risk persons and self-examinations in (1) the United States, (2) New Zealand, (3) Australia, (4) the Netherlands, (5) Italy, (6) Sweden, (7) Scotland, and (8) Germany. Key challenges in melanoma screening are (1) who can perform screening, (2) who should

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be screened, and (3) where screenings should occur. Professional organizations differ in their recommendations regarding screening. Some recommend screening for the general population, while some recommend screening for high-risk groups only. The authors conclude that screening and early detection programs could potentially save lives otherwise lost to melanoma. ·

Who Gets Melanoma and Why Source: in Melanoma: Prevention, Detection, and Treatment. Poole, C.; Guerry, D., IV. New Haven, CT, Yale University Press, pp. 21-36, 1998. Contact: Yale University Press, 92A Yale Station, New Haven, CT 06520. (203) 432-0960. Summary: Who Gets Melanoma and Why, a chapter in Melanoma: Prevention, Detection, and Treatment, presents information on the risks for and epidemiology of melanoma. Epidemiologists have pinpointed certain characteristics that, whether they occur separately or in conjunction, predict who is likely to get melanoma. These include (1) a sun-sensitive skin type that may freckle easily, (2) a history of spending too much time in the sun, (3) many common moles or any dysplastic moles, (4) a personal or family history of any of the common kinds of skin cancer (squamous or basal cell carcinoma), and (5) a personal or family history of melanoma. Other less important yet still influential factors include the person's gender, geographical location, and age. The risk associated with each risk factor itself is not great; however, individuals who possess multiple melanoma risk factors may be at dramatically increased risk. The chapter discusses (1) the role of the sun and ultraviolet radiation, (2) the skin types that are susceptible to melanoma, (3) the types of sun exposure that cause melanoma, (4) whether all sun exposure is harmful to most people, (5) what moles are, (6) when a mole should be removed, (7) whether melanoma is hereditary, (8) whether a history of skin cancer is a risk factor for developing melanoma, (9) whether pregnancy is a risk factor for melanoma, (10) whether taking oral contraceptives or undergoing hormone replacement therapy can increase a woman's risk of developing melanoma, and (11) if where a person lives affects whether they might develop melanoma.

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Finding Early Melanoma Source: in Melanoma: Prevention, Detection, and Treatment. Poole, C.; Guerry, D., IV. New Haven, CT, Yale University Press, pp. 37-49, 1998. Contact: Yale University Press, 92A Yale Station, New Haven, CT 06520. (203) 432-0960.

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Summary: Finding Early Melanoma, a chapter in Melanoma: Prevention, Detection, and Treatment, explains that early detection is one of the best lines of defense against melanoma and should be made a top priority in the battle against the disease. It is important to teach the public, primary health care providers, and body care practitioners how to recognize incipient melanoma. Melanoma is always curable when completely removed before it develops the capacity to spread. Regular skin examination is crucial to finding early melanoma at its most curable stage, and it is important for individuals to set up a schedule of selfexaminations. Skin examinations should occur in a brightly lighted room. Tools needed include a hand-held flashlight, a full-length mirror, a hand mirror, and two stools or chairs. These tools are necessary for examining every inch of the body. Early melanoma can look like an irregular, inflamed, or spreading flat mole. Many melanomas can change noticeably over weeks or months. Many general practitioners will not conduct a skin examination unless asked, nor do they teach skin selfexamination techniques. Most melanomas appear on the backs of people of both sexes, the chests and abdomens of men, and the legs of women. It is important to get any questionable lesions checked, because research has shown that a long lag time between diagnosis and treatment can result in a less favorable prognosis. Health professionals recommend that if people spot a potential melanoma on someone else, they should point it out immediately and recommend treatment. Since 1985, the American Academy of Dermatology has operated a free screening program, and 750,000 people have received screening. A current dilemma in the field of skin cancer screening is how to reach the individuals at risk and convince them to get their skin checked. ·

Future Promise: Prevention of Melanoma Source: in Melanoma: Prevention, Detection, and Treatment. Poole, C.; Guerry, D., IV. New Haven, CT, Yale University Press, pp. 98-114, 1998. Contact: Yale University Press, 92A Yale Station, New Haven, CT 06520. (203) 432-0960. Summary: Future Promise: Prevention of Melanoma, a chapter in Melanoma: Prevention, Detection, and Treatment, explores how to change attitudes about sun exposure and work to prevent melanoma. In the United States, large segments of the population know nothing about what melanoma is or what causes it, so they lack the motivation to try to prevent it. In Australia, most individuals know about melanoma because of the extremely high incidence of the disease in their country and the nationwide SunSmart campaign. The Centers for Disease Control and Prevention has given the American Academy of Dermatology funding to

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follow Australia's lead in providing a comprehensive educational program to spread the message that sun protection saves lives. Parents should learn about protecting their children before their children are born, and they can set an example early on for their children by taking appropriate precautions. Educational efforts in school are also important because they can teach children to play in the shade, wear hats, and put on sunscreen. There should be sun-safe policies for summer camps, where children are typically exposed to a great deal of sun. Adolescents are the least likely group to protect themselves against the sun and most likely to suffer from overexposure. A priority in Australia's program is to help change young adults' attitudes about sun behavior. The melanoma mortality rate for men is higher than it is for women, mainly because many men delay seeking a doctor's advice and are likely to ignore it. There needs to be a profound cultural shift in attitudes about the sun. This may mean getting certain powerful groups involved, including the media and the sports industry (which has been effective in Australia). Because of chlorofluorocarbons in the atmosphere, there are holes in the ozone layer that increase people's exposure to ultraviolet (UV) radiation. The situation will slowly improve as the ozone layer heals itself following decreased use of chlorofluorocarbons. Although natural tanning acts as a weak sunblock and may provide some protection from melanoma, physicians are quick to point out that sun exposure damages the skin. Both UV-A and UV-B are dangerous to the skin, and sunscreens that protect against both are important. Prevention specialists feel that sunscreens should be used only as an adjunct to habits capitalizing on natural sun protection. Following the guidelines for sunscreen use and application is essential. Generously applying a broad-spectrum sunscreen is important, as is following the UV index forecast to avoid sunlight during peak hours. ·

Attitudes and Behaviour Towards Sun Exposure: Implications for Melanoma Prevention Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J.; Stern, R.S.; MacKie, R.M.; Weinstock, W.A.; eds. Oxford, England, Blackwell Science Ltd., pp. 144-151, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 02148-5018. (800) 759-6102; (617) 388-8250. FAX: (617) 3888255. Summary: Attitudes and Behaviour Towards Sun Exposure: Implications for Melanoma Prevention, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, considers the knowledge, attitudes, and behavior towards sun exposure in developed countries. Sun behavior and

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practice of protective measures differ widely from country to country. Any dermatologist dedicated to primary prevention must bear several facts in mind. First, it is difficult to extrapolate data from one country to another. Tanning is a social phenomenon, and the risk of melanoma creates a psychological conflict between the desire to be tanned and the dangers of sun exposure. Awareness of one's sun sensitivity is a determinant. Use of sunscreen is also a social phenomenon. There is a gap between what people know, what they intend to do, and what they do. Objective evaluation of primary melanoma prevention campaigns is difficult. Prevention campaigning is resource intensive. Many melanoma prevention campaigns have been successfully conducted in schools. An interaction between primary prevention and screening campaigns is inevitable. Campaigns aimed at primary melanoma prevention by reducing sun exposure are hindered by uncertainties involving the most suitable message, the most effective means of delivery, the actual impact on behavior, the durability of changes, and the difficulty of measuring long-term effects. Experience indicates that, although interesting results hav e been obtained in countries that have applied intense resources, outcome depends on psychosocial factors. ·

Lack of Efficacy of Common Sunscreens in Melanoma Prevention Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J.; Stern, R.S.; MacKie, R.M.; Weinstock, W.A.; eds. Oxford, England, Blackwell Science Ltd., pp. 151-159, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 02148-5018. (800) 759-6102; (617) 388-8250. FAX: (617) 3888255. Summary: Lack of Efficacy of Common Sunscreens in Melanoma Prevention, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, discusses the incidence of malignant melanoma in the United States, which has increased faster than any other cancer during the past 3 decades. Worldwide, the countries where chemical sunscreens have been widely promoted and adopted have experienced the greatest rise in cutaneous melanoma, with a rise in death rates following the acceleration in incidence rates by 5 to 10 years. Experimental studies of sunscreens mainly have used artificial sources of irradiation designed to maximize ultraviolet B exposures. Analysis of the absorption spectrum of the sunscreen ingredient PABA revealed that it absorbed ultraviolet B, but provided no absorption in the ultraviolet A range. Three epidemiological studies found significantly higher risk of melanoma associated with sunscreen use in both sexes combined. Two others reported significantly elevated odds ratios associated with use of sunscreens in men and no

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favorable association with sunscreen use in women. One study reported a higher risk of basal cell carcinoma in women who used sunscreens, compared to nonusers among women spending over 8 hours outdoors. The findings help to explain some of the paradoxes in the epidemiology of melanoma, particularly its stronger association with skin pigmentation than with latitude. Mortality rates for skin malignancies in the United States did not rise immediately after introduction of sunscreens, but rather after an appropriate latency period. For most individuals, moderate year-round exposure to the sun is desirable to stimulate accommodation and protective pigmentation, as well as for adequate synthesis of vitamin D in the skin. Traditional measures for reducing solar overexposure, such as wearing of hats and clothing, would continue to be appropriate for those with unaccommodated skin who must remain in the sun for extended periods. ·

Role of Sunscreen Lotions in Melanoma Prevention Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J.; Stern, R.S.; MacKie, R.M.; Weinstock, W.A.; eds. Oxford, England, Blackwell Science Ltd., pp. 159-163, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 02148-5018. (800) 759-6102; (617) 388-8250. FAX: (617) 3888255. Summary: Role of Sunscreen Lotions in Melanoma Prevention, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, notes that using sunscreens has not yet been established to be beneficial, and the problem may indeed be more complex than is generally appreciated. Persons using sunscreen may compensate for sunscreen use by increasing their time in the sun or decreasing the use of protective clothing. Sunscreen use may increase the intermittency of ultraviolet exposure to the skin, which could adversely affect melanoma risk. Present evidence suggests that sunscreens are effective for prevention of melanoma, but several areas of uncertainty must be resolved before this conclusion can be considered established. It would therefore be prudent to recommend to the general public that (1) sunscreens not be used to increase exposure to the sun, (2) consistent use is preferable, and (3) broad spectrum sunscreens are preferable to those that primarily protect against the ultraviolet B portion of the spectrum.

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Screening for Melanoma: Methods, Advantages and Limits Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J.; Stern, R.S.; MacKie, R.M.; Weinstock, W.A.; eds. Oxford, England, Blackwell Science Ltd., pp. 166-173, 1997.

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Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 02148-5018. (800) 759-6102; (617) 388-8250. FAX: (617)3888255. Summary: Screening for Melanoma: Methods, Advantages and Limits, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, notes that in recent years public health bodies and the medical profession have been contemplating and initiating educational programs directed at primary prevention and early detection. Screening programs for skin cancer and melanoma are increasing in number. To effectively develop a screening program, certain conditions must be met: (1) The condition sought should be an important health problem; (2) there should be an accepted treatment for patients with recognized disease; (3) facilities for diagnosis and treatment should be available; (4) there should be a recognizable latent or early symptomatic stage; (5) there should be a suitable test or examination; (6) the test should be acceptable to the population; (7) the natural history of the condition, including development from latent to declared disease, should be adequately understood; (8) the cost of screening, including diagnosis and treatment of positive screens, should be economically balanced in relation to possible expenditures on medical care as a whole; and (9) screening should be a continuing process and not a single occasion project. There are several screening procedures for skin cancer and melanoma. Targeting high-risk persons should enhance the efficiency of the process. Volunteer screening campaigns may reach only a small section of the population. The key components of the successful screening intervention include (1) an organizational forum fo r program development, (2) an intensive precampaign public education program, (3) dedicated personnel, (4) suitable locations, (5) narrowing the scope of the screen by focusing on melanoma only, (6) understanding that complete skin examinations are time-consuming and unproductive, (7) rigorous followup of positive screens, (8) use of overall outcome measures, and (9) assessment of actual and hidden costs. ·

Causes for the Delay in Diagnosis of Melanoma Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J.; Stern, R.S.; MacKie, R.M.; Weinstock, W.A.; eds. Oxford, England, Blackwell Science Ltd., pp. 177-183, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 02148-5018. (800) 759-6102; (617) 388-8250. FAX: (617) 3888255. Summary: Causes for the Delay in Diagnosis of Melanoma, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, indicates that the

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delay in diagnosis may be in the order of 1 year. If the goal of early melanoma detection is to be achieved, it is critical that the factors that cause a delay in the diagnosis be understood so that appropriate interventions are instituted. In order to understand the reason for the delay in diagnosis, several questions must be addressed, including (1) who makes the diagnosis, (2) who is able to make the diagnosis, (3) why the delay, and (4) was it caused by the patient or physician or both. Identification of the person who detects, or fails to detect, melanoma is important if we are to decrease the time to diagnosis and to organize educational efforts optimally. The ability of a physician to accurately diagnose or suspect melanoma in a patient and perform a biopsy/excision or make a timely referral is a critical factor in improving the time to diagnosis. A lower diagnostic accuracy revealed by nondermatologists in studies indicates a need for improved professional education, given the increasing role of the primary caregiver in the initial assessment of the patient in the United States and their alreadyprominent role in other countries. Given the importance of early diagnosis, and the difficulties in clinical diagnosis, even among skin cancer specialists with extensive experience, there has been on-going research into clinical techniques that may improve diagnostic accuracy.

General Home References In addition to references for melanoma, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Cancer: 50 Essential Things to Do by Greg Anderson, O. Carl Simonton; Paperback - 184 pages; Revised & Updated edition (August 1999), Plume; ISBN: 0452280745; http://www.amazon.com/exec/obidos/ASIN/0452280745/icongroupinterna · Cancer Encyclopedia -- Collections of Anti-Cancer & Anti-Carcinogenic Agents, Chemicals, Drugs and Substances by John C. Bartone; Paperback (January 2002), ABBE Publishers Association of Washington, DC; ISBN: 0788326791; http://www.amazon.com/exec/obidos/ASIN/0788326791/icongroupinterna · Cancer Sourcebook: Basic Consumer Health Information About Major Forms and Stages of Cancer by Edward J. Prucha (Editor); Library Binding - 1100 pages, 3rd edition (August 1, 2000), Omnigraphics, Inc.; ISBN: 0780802276; http://www.amazon.com/exec/obidos/ASIN/0780802276/icongroupinterna

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· Cancer Supportive Care: A Comprehensive Guide for Patients and Their Families by Ernest H. Rosenbaum, M.D., Isadora Rosenbaum, M.A.; Paperback - 472 pages (November 5, 1998), Somerville House Books Limited; ISBN: 1894042115; http://www.amazon.com/exec/obidos/ASIN/1894042115/icongroupinterna · Cancer Symptom Management: Patient Self-Care Guides (Book with CD-ROM for Windows & Macintosh) by Connie Henke Yarbro (Editor), et al; CD-ROM - 264 pages, 2nd Book & CD-Rom edition (January 15, 2000), Jones & Bartlett Publishing; ISBN: 0763711675; http://www.amazon.com/exec/obidos/ASIN/0763711675/icongroupinterna · Diagnosis Cancer: Your Guide Through the First Few Months by Wendy Schlessel Harpham, Ann Bliss Pilcher (Illustrator); Paperback: 230 pages; Revised & Updated edition (November 1997), .W. Norton & Company; ISBN: 0393316912; http://www.amazon.com/exec/obidos/ASIN/0393316912/icongroupinterna · The Human Side of Cancer: Living with Hope, Coping with Uncertainty by Jimmie C. Holland, M.D., Sheldon Lewis; Paperback - 368 pages (October 2, 2001), Quill; ISBN: 006093042X; http://www.amazon.com/exec/obidos/ASIN/006093042X/icongroupinterna

Vocabulary Builder Abdomen: The part of the body that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Chlorofluorocarbons: A series of hydrocarbons containing both chlorine and fluorine. These have been used as refrigerants, blowing agents, cleaning fluids, solvents, and as fire extinguishing agents. They have been shown to cause stratospheric ozone depletion and have been banned for many uses. [NIH]

Contraceptive: conception. [EU]

An agent that diminishes the likelihood of or prevents

Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [NIH]

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CHAPTER 7. MULTIMEDIA ON MELANOMA Overview Information on melanoma can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on melanoma. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine. If you see an interesting item, visit your local medical library to check on the availability of the title.

Video Recordings Most diseases do not have a video dedicated to them. If they do, they are often rather technical in nature. An excellent source of multimedia information on melanoma is the Combined Health Information Database. You will need to limit your search to “video recording” and “melanoma” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” By making these selections and typing “melanoma” (or synonyms) into the “For these words:” box, you will only receive results on video productions. The following is a typical result when searching for video recordings on melanoma:

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Detecting Early Melanoma Source: Atlanta, GA, American Cancer Society, 1 VHS videotape, 13:25min., 1990. Contact: American Cancer Society, 1599 Clifton Road, NE., Atlanta, GA 30329. ACS Code: 3782.05. Summary: Detecting Early Melanoma is a videotape, with narrative provided. A dermatologist discuses skin cancer risks, symptoms, and prevention. People today have a 1 in 120 risk of developing malignant melanoma, the most serious form of skin cancer. Malignant melanoma tends to metastasize, but is curable if found in its early stages. The physician needs good eyes, good light, and perhaps a magnifying glass, and should use these tools to perform a thorough skin examination on patients. Many melanomas are found on the upper back in men and on the legs in women, but skin cancer can occur on any body part. The ABCD Rule of signs is given: Look for moles or growths that are Asymmetrical, have Border irregularity, have Color variegation, and are greater than 6 millimeters in Diameter. Color slides in this video demonstrate the different appearances of moles that are normal versus those that are skin cancers. Other signs of cancer are crusting, bleeding, not healing, or moles with a blue/black color; these should all be biopsied. Dysplastic nevi may be cancer precursors and should be followed carefully. Biopsies can usually be done with local anesthesia in the office. Risks for developing melanoma include fair skin, previous personal or family history, immunosuppressive patients, and/or those who had blistering sunburns, especially early in life. Blacks can develop skin cancer, under their nails and on palms and soles. A nurse demonstrates teaching a male patient how to do a thorough skin self examination. Patients can also keep body charts to note location of moles. Prevention is stressed, including avoidance of tanning, use of sunscreen, wearing protective clothing in the sun, and avoiding midday sun.

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Skin Cancer: Preventable and Curable Source: New York, NY, Skin Cancer Foundation, 15-minute VHS videotape, 1990. Contact: Skin Cancer Foundation, P.O. Box 561, New York, NY 10156. Summary: Skin Cancer: Preventable and Curable, narrated by talk show host Dick Cavett, teaches the viewer about risk factors for developing skin cancer, warning signs, how to identify skin cancer, and how to prevent it. The video discusses the importance of the ozone layer and ultraviolet rays (UVA and UVB), and presents a graph showing how deeply each type of ray penetrates skin. Excess sun exposure causes

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sunburn, premature aging, wrinkles, and 90 percent of all skin cancers. Anyone can get skin cancer, but some people are more vulnerable than others. The risk is greatest for those classified as having skin type one: Fair skin; red, light brown, or blonde hair; green, blue or gray eyes. Skin types are classified up to type six: Having dark skin and eyes and never burning. Risk factors also include having a history of blistering burns in childhood, or family history of skin cancer. Types of skin cancer include basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Pictures of actual cases are shown for each type of cancer. Each is treatable and curable if detected early, even malignant melanoma. Untreated, there is a chance of metastasis and eventual death. Skin selfexamination is very important. One can use a hand mirror to check hardto-see areas, and a blow dryer to look at the scalp. Look for any changes in the skin, such as changes to a mole or growth of a new mole or spot. Notice if the mole or spot is asymmetrical, has irregular borders, has changes in color, and is bigger than a pencil eraser. If one sees anything that is suspicious, one should see a physician right away for evaluation. Tips on preventing skin cancer include avoiding peak sun hours, wearing protective clothing and a sunscreen of Sun Protection Factor 15 or higher, protecting children from sun exposure, not working on a tan either outdoors or at a tanning salon, and performing regular skin examination. The address of the Skin Cancer Foundation, P.O. Box 561, New York, NY 10156, is given. ·

Sun safety: A growing health concern Source: Itasca, NY: National Safety Council. 1999. 1 videotape (11:46 minutes, VHS 1/2 inch). Contact: Available from National Maternal and Child Health Clearinghouse, 2070 Chain Bridge Road, Suite 450, Vienna, VA 221822536. Telephone: (703) 356-1964 or (888) 434-4MCH / fax: (703) 821-2098 / e-mail: [email protected] / Web site: http://www.nmchc.org. Summary: This videotape discusses safe exposure to the sun. Topics include sunburn, melanoma, and other risks.

Bibliography: Multimedia on Melanoma The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in melanoma (or synonyms). Then, in

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the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on melanoma. For more information, follow the hyperlink indicated: ·

Breakthroughs in malignant melanoma. Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic and St. Joseph's Hospital; Year: 1982; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1982.

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Contemporary aspects of malignant melanoma. Source: Blake Cady, Samuel L. Moschella, Merle A. Legg; Year: 1974; Format: Slide; New York: Medcom, c1974.

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Control and prevention of malignant melanoma: a program for melanoma-prone families. Source: the Pigmented Lesion Study Group, the University of Pennsylvania [and] the Environmental Epidemiology Branch of the National Cancer Institute; Year: 1981; Format: Videorecording; Washington, DC: National Audiovisual Center, [1981]

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Cutaneous melanoma. Source: Dutch National Cancer Education Project; Year: 1985; Format: Slide; [Amsterdam]: Netherlands Cancer Foundation, c1985.

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Dysplastic nevi and hereditary melanoma: a program for clinicians. Source: Pigmented Lesion Clinical Group, University of Pennsylvania and the Environmental Epidemiology Branch, Family Studies Unit, National Cancer Institute; Year: 1981; Format: Videorecording; Washington, D.C.: National Audiovisual Center, [1981]

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Dysplastic nevi and melanoma: a program for pathologists. Source: Pigmented Lesion Study Group, the University of Pennsylvania, the Environmental Epidemiology Branch of the National Cancer Institute; Year: 1981; Format: Videorecording; Washington, D.C.: National Audiovisual Center, [1981]

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Early diagnosis of malignant melanoma. Source: U. S. Public Health Service; produced by National Medical Audiovisual Center, in cooperation with the Institute for Dermatologic Communication and Education; Year: 1968; Format: Motion picture; [Washington]: Public Health Service; [Atlanta: for loan by National Medical Audiovisual Center], 1968.

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Extended surgery for cancer of the colon, cancer of the head and neck, and melanoma: indications and techniques. Source: American College of Surgeons; Year: 1978; Format: Sound recording; [Chicago]: The College, [1978]

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Malignant melanoma: diagnosis and staging. Source: Everett V. Sugarbaker; Year: 1979; Format: Slide; Westport, Conn.: MEDED, c1979.

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Malignant melanoma: biology, diagnosis, therapy. Source: Larry Nathanson; Year: 1974; Format: Slide; New York: Medcom, c1974.

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Malignant melanoma: histologic interpretation and prognostication. Source: American Society of Clinical Pathologists; Year: 1975; Format: Videorecording; [Chicago]: The Society, c1975.

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Malignant melanoma and its clinical simulators. Source: Darrell S. Rigel; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986.

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Malignant melanoma of the choroid. Source: Ohio State University; [produced by] its Media Audio-Visual and Television Center; Year: 1975; Format: Videorecording; Columbus: The University; [San Francisco, Calif.: for sale by American Academy of Ophthalmology], c1975.

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Malignant melanoma. Source: Department of Orthopedic Surgery, the Mt. Sinai Medical Center, Cleveland, Ohio; Year: 1987; Format: Slide; [Park Ridge, Ill.]: American Academy of Orthopedic Surgeons, [1987]

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Management of melanoma. Source: American College of Surgeons; Year: 1978; Format: Sound recording; [Chicago]: The College, [1978]

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Melanoma prevention and screening : the Australian approach. Source: Robin Marks, John Kelly; Year: 1991; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1991.

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Melanomas: diagnosis and treatment. Source: American Cancer Society; [made by] Wexler Films; Year: 1973; Format: Motion picture; New York: The Society, [1973]

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Melanomas of the eye. Source: [Daniel M. Albert, Carmen A. Puliafito]; Year: 1981; Format: Slide; Philadelphia, PA.: F.A. Davis, c1981.

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Moles and melanoma. Source: Bureau of Aeronautics, Navy Department, United States of America; Year: 1945; Format: Motion picture; United States: The Bureau, 1945.

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New approach to malignant melanoma. Source: University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute; Year: 1976; Format: Videorecording; Houston: The Institute, 1976.

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Nursing management of the patient with melanoma. Source: Roswell Park Memorial Institute, in cooperation with the Lakes Area Regional Medical Program; Year: 1974; Format: Slide; [Buffalo]: Communications in Learning, 1974.

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Primary cutaneous malignant melanomas: recognition and management. Source: Thomas B. Fitzpatrick ... [et al.]; Year: 1976; Format: Slide; Evanston, Ill.: American Academy of Dermatology, c1976.

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Regional perfusion for malignant melanoma. Source: Committee on Medical Motion Pictures, American College of Surgeons; produced by

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Davis & Geck; Year: 1970; Format: Motion picture; Danbury, Conn.: Davis ; Geck; [Atlanta: for loan by National Medical Audiovisual Center], 1970. ·

Skin diseases: scabies, malignant melanoma: a report. Source: Donald P. Lookingbill; [made by] Penn State Television; Year: 1977; Format: Videorecording; University Park, Pa.: Pennsylvania State University: [for loan or sale by its Audio-Visual Services], c1977.

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Temporal melanoma with left parotidectomy and left radical neck dissection. Source: Mayo Clinic; Year: 1964; Format: Motion picture; Rochester, Minn.: The Clinic, 1964.

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Treatment of melanoma. Source: Roswell Park Memorial Institute, in cooperation with Lakes Area Regional Medical Program; Year: 1974; Format: Slide; [Buffalo]: Communications in Learning, 1974.

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Wide local excision of melanoma and elective groin dissection. Source: produced by Ciné-Med; Year: 1993; Format: Videorecording; Woodbury, Conn.: Ciné-Med, c1993.

Vocabulary Builder Anesthesia: Loss of feeling or awareness. Local anesthetics cause loss of feeling in a part of the body. General anesthetics put the person to sleep. [NIH] Immunosuppressive: responses. [NIH]

Describes the ability to lower immune system

Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Scabies: A contagious dermatitis of humans and various wild and domestic animals caused by the itch mite, Sarcoptes scabiei, transmitted by close contact, and characterized by a papular eruption over tiny, raised sinuous burrows (cuniculi) produced by digging into the upper layer of the epidermis by the egg-laying female mite, which is accompanied by intense pruritus and sometimes associated with eczema from scratching and secondary bacterial infection. Called also the itch and seven-year itch. [EU]

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CHAPTER 8. PERIODICALS AND NEWS ON MELANOMA Overview Keeping up on the news relating to melanoma can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on melanoma. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover melanoma beyond and including those which are published by patient associations mentioned earlier. We will first focus on news services, and then on periodicals. News services, press releases, and newsletters generally use more accessible language, so if you do chose to subscribe to one of the more technical periodicals, make sure that it uses language you can easily follow.

News Services & Press Releases Well before articles show up in newsletters or the popular press, they may appear in the form of a press release or a public relations announcement. One of the simplest ways of tracking press releases on melanoma is to search the news wires. News wires are used by professional journalists, and have existed since the invention of the telegraph. Today, there are several major “wires” that are used by companies, universities, and other organizations to announce new medical breakthroughs. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing.

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PR Newswire Perhaps the broadest of the wires is PR Newswire Association, Inc. To access this archive, simply go to http://www.prnewswire.com. Below the search box, select the option “The last 30 days.” In the search box, type “melanoma” or synonyms. The search results are shown by order of relevance. When reading these press releases, do not forget that the sponsor of the release may be a company or organization that is trying to sell a particular product or therapy. Their views, therefore, may be biased. The following is typical of press releases that can be found on PR Newswire: ·

Medarex Initiates Phase II Clinical Trials of MDX-010 for Metastatic Melanoma and Prostate Cancer Summary: Princeton, N.J., Oct. 29 /PRNewswire-FirstCall/ -- Medarex, Inc. (Nasdaq: MEDX) today announced the initiation of two Phase II clinical trials of MDX-010, one in patients with metastatic melanoma and one in patients with hormone refractory prostate cancer. The two randomized, multi-dose Phase II studies are designed to assess the potential anti-tumor activity of MDX-010. The metastatic melanoma Phase II trial will study MDX-010 both as a single agent and in combination with DTIC (dacarbazine). The trial is expected to initially accrue a total of 46 chemotherapy naive patients with metastatic disease. MDX-010 will be given in a regimen of four monthly intravenous infusions of 3.0 mg/kg alone or in combination with DTIC. Patients will be followed until tumor progression and will be evaluated based on objective tumor responses. The prostate cancer Phase II trial will study MDX-010 as a single agent and in combination with Taxotere(R) (docetaxel). The trial is expected to initially accrue 40 chemotherapy naive patients with hormone refractory prostate cancer. MDX-010 will be given in a regimen of four monthly intravenous infusions of 3.0 mg/kg alone or in combination with Taxotere. Patients will be followed until tumor progression and will be evaluated based on decreases in serum prostate specific antigen (PSA) and tumor regression as well as time to tumor progression. An elevated PSA level is considered a marker of disease burden in prostate cancer patients. These Phase II studies are in addition to Medarex's ongoing trials with MDX-010 in combination with three different melanoma vaccines. A Phase II trial of MDX-010 in combination with a melanoma peptide

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vaccine based on gp100 is open to accrue up to 55 patients with metastatic melanoma. In this trial patients receive MDX-010 every three weeks together with the melanoma peptide vaccine. A Phase I/II trial of MDX-010 in combination with a different melanoma peptide vaccine based on multiple melanoma antigens has completed the full enrollment of 19 patients with advanced resected melanoma. Medarex also has completed enrollment of all 14 patients in a Phase I/II study of MDX-010 in combination with the Melacine(R) vaccine for melanoma. "By releasing the immune system's emergency brake, we believe that MDX-010 has broad potential for the treatment of a variety of cancers," said Donald L. Drakeman, President and CEO of Medarex. "We look forward to the opportunity to test this novel product further in these Phase II clinical trials." Recent Clinical Data Phase I/II data presented earlier this year by Medarex at the American Society of Clinical Oncology (ASCO) meeting indicated that a single 3.0 mg/kg dose of MDX-010 alone may induce tumor regression in some patients with metastatic melanoma and hormone refractory prostate cancer. Of the 17 patients in the metastatic melanoma trial, two patients achieved partial responses, per the RECIST (Response Evaluation Criteria in Solid Tumor) definition, one of which experienced a decrease of greater than 90% of tumor volume lasting over five months. One patient achieved a minor response lasting four months, and two patients experienced stable disease lasting three months. Additional mixed responses were seen. Of the 14 patients in the hormone refractory prostate cancer trial, two of seven chemo-naive patients experienced a greater than 50% reduction in serum PSA measurement that lasted from five months, and one patient with bone pain experienced significant improvement in his symptoms. The data indicated that the product was generally well tolerated. Across both studies, mild to moderate adverse events, including a rash or itching were experienced by 11 (35%) patients. Further signs of immunologic activity directed at tumors included tumor necrosis, inflammatory reactions at tumor sites and immune mediated rash.

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Reuters The Reuters’ Medical News database can be very useful in exploring news archives relating to melanoma. While some of the listed articles are free to view, others can be purchased for a nominal fee. To access this archive, go to http://www.reutershealth.com/frame2/arch.html and search by “melanoma” (or synonyms). The following was recently listed in this archive for melanoma: ·

Dermatoscope plus computer imaging can yield rapid melanoma diagnosis Source: Reuters Industry Breifing Date: November 21, 2002 http://www.reuters.gov/archive/2002/11/21/business/links/20021121 drgd010.html

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Adoptive T cell therapy effective against metastatic melanoma Source: Reuters Medical News Date: November 12, 2002 http://www.reuters.gov/archive/2002/11/12/professional/links/20021 112drgd001.html

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Wide excision margins yield no survival benefit for thin melanomas Source: Reuters Medical News Date: October 29, 2002 http://www.reuters.gov/archive/2002/10/29/professional/links/20021 029clin019.html

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Fotemustine has some advantages over dacarbazine in treating melanoma Source: Reuters Industry Breifing Date: October 23, 2002 http://www.reuters.gov/archive/2002/10/23/business/links/20021023 drgd001.html

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Age, gender affect melanoma chemo success Source: Reuters Health eLine Date: October 23, 2002 http://www.reuters.gov/archive/2002/10/23/eline/links/20021023elin 032.html

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Age and gender affect efficacy of chemotherapy for melanoma Source: Reuters Medical News Date: October 23, 2002 http://www.reuters.gov/archive/2002/10/23/professional/links/20021 023clin018.html

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Phase III data for Maxim's Ceplene supports sub-population treatment in melanoma Source: Reuters Industry Breifing Date: October 21, 2002 http://www.reuters.gov/archive/2002/10/21/business/links/20021021 drgd003.html

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Previous vaccinia and BCG vaccination seems to protect against melanoma Source: Reuters Industry Breifing Date: October 15, 2002 http://www.reuters.gov/archive/2002/10/15/business/links/20021015 epid007.html

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Melanoma screening should target men over 50 years of age Source: Reuters Medical News Date: October 15, 2002 http://www.reuters.gov/archive/2002/10/15/professional/links/20021 015publ001.html

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Autologous peptide vaccine produces response in some cases of metastatic melanoma Source: Reuters Industry Breifing Date: October 14, 2002 http://www.reuters.gov/archive/2002/10/14/business/links/20021014 drgd003.html

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Younger folks see decline in melanoma mortality Source: Reuters Health eLine Date: October 08, 2002 http://www.reuters.gov/archive/2002/10/08/eline/links/20021008elin 021.html

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Late recurrence of melanoma to be expected in significant portion of patients Source: Reuters Medical News Date: October 07, 2002 http://www.reuters.gov/archive/2002/10/07/professional/links/20021 007epid009.html

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Protarga to start phase III metastatic melanoma trial Source: Reuters Industry Breifing Date: October 03, 2002 http://www.reuters.gov/archive/2002/10/03/business/links/20021003 drgd002.html

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Peptide sensitizes melanoma cells to chemotherapy-induced apoptosis Source: Reuters Industry Breifing Date: September 26, 2002 http://www.reuters.gov/archive/2002/09/26/business/links/20020926 scie001.html

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BioVex licenses antigens for melanoma vaccine from US government Source: Reuters Industry Breifing Date: September 24, 2002 http://www.reuters.gov/archive/2002/09/24/business/links/20020924 inds005.html

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Melanoma patients respond to T-cell transplant after lymphodepletion Source: Reuters Industry Breifing Date: September 19, 2002 http://www.reuters.gov/archive/2002/09/19/business/links/20020919 scie002.html

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Allogeneic stem cell transplant induces regression in metastatic melanoma Source: Reuters Medical News Date: September 02, 2002 http://www.reuters.gov/archive/2002/09/02/professional/links/20020 902scie005.html

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Low serum HLA-DR predicts disease progression with early-stage melanoma Source: Reuters Medical News Date: August 21, 2002 http://www.reuters.gov/archive/2002/08/21/professional/links/20020 821clin019.html

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Statin increases melanoma sensitivity to doxorubicin by augmenting apoptosis Source: Reuters Industry Breifing Date: July 29, 2002 http://www.reuters.gov/archive/2002/07/29/business/links/20020729 scie001.html

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Radiotherapy plus thermotherapy provides good local control of uveal melanoma Source: Reuters Industry Breifing Date: July 26, 2002 http://www.reuters.gov/archive/2002/07/26/business/links/20020726 clin006.html

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US grants orphan drug status to melanoma vaccine Source: Reuters Medical News Date: July 23, 2002 http://www.reuters.gov/archive/2002/07/23/professional/links/20020 723rglt006.html

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Antigenics gets US orphan drug status for melanoma vaccine Source: Reuters Industry Breifing Date: July 23, 2002 http://www.reuters.gov/archive/2002/07/23/business/links/20020723 rglt003.html

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Galectin-9 linked to less aggressive malignant melanoma Source: Reuters Medical News Date: July 17, 2002 http://www.reuters.gov/archive/2002/07/17/professional/links/20020 717clin008.html

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Malignant melanoma more aggressive in HIV-positive patients Source: Reuters Medical News Date: July 04, 2002 http://www.reuters.gov/archive/2002/07/04/professional/links/20020 704epid004.html

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Sunscreen use not tied to malignant melanoma Source: Reuters Medical News Date: July 01, 2002 http://www.reuters.gov/archive/2002/07/01/professional/links/20020 701epid001.html

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Cutaneous melanoma in children requires early diagnosis and treatment Source: Reuters Medical News Date: June 26, 2002 http://www.reuters.gov/archive/2002/06/26/professional/links/20020 626epid006.html

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Expression of inherited form of melanoma varies by geographic location Source: Reuters Medical News Date: June 18, 2002 http://www.reuters.gov/archive/2002/06/18/professional/links/20020 618epid005.html

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Temozolomide plus thalidomide well tolerated in melanoma patients Source: Reuters Industry Breifing Date: June 14, 2002 http://www.reuters.gov/archive/2002/06/14/business/links/20020614 clin004.html

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Coley begins phase I/II trial of melanoma drug Source: Reuters Industry Breifing Date: June 13, 2002 http://www.reuters.gov/archive/2002/06/13/business/links/20020613 drgd006.html

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Cancer deaths due to melanoma seen increasing in Spain Source: Reuters Medical News Date: June 13, 2002 http://www.reuters.gov/archive/2002/06/13/professional/links/20020 613epid006.html

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Thin melanomas with extensive regression show increased metastatic potential Source: Reuters Medical News Date: June 12, 2002 http://www.reuters.gov/archive/2002/06/12/professional/links/20020 612clin014.html

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Mutations of BRAF gene linked to malignant melanoma Source: Reuters Industry Breifing Date: June 10, 2002 http://www.reuters.gov/archive/2002/06/10/business/links/20020610 scie003.html

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Vaccination prolongs relapse-free period in patients with advanced melanoma Source: Reuters Medical News Date: June 05, 2002 http://www.reuters.gov/archive/2002/06/05/professional/links/20020 605drgd001.html

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Antisense therapy overcomes melanoma chemoresistance factor Source: Reuters Medical News Date: May 21, 2002 http://www.reuters.gov/archive/2002/05/21/professional/links/20020 521scie002.html

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Australia unveils melanoma detection device Source: Reuters Industry Breifing Date: May 07, 2002 http://www.reuters.gov/archive/2002/05/07/business/links/20020507 drgd001.html

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CancerVax stops enrollment in melanoma vaccine study on FDA data request Source: Reuters Industry Breifing Date: May 02, 2002 http://www.reuters.gov/archive/2002/05/02/business/links/20020502 drgd008.html

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Antigenics starts phase III enrollment of fast-track melanoma vaccine Source: Reuters Industry Breifing Date: May 02, 2002 http://www.reuters.gov/archive/2002/05/02/business/links/20020502 drgd005.html

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Biochemotherapy extends survival in metastatic melanoma Source: Reuters Industry Breifing Date: May 01, 2002 http://www.reuters.gov/archive/2002/05/01/business/links/20020501 clin006.html

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Little benefit seen with adjuvant interferon-alpha for malignant melanoma Source: Reuters Industry Breifing Date: April 23, 2002 http://www.reuters.gov/archive/2002/04/23/business/links/20020423 clin008.html

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Drug shows early promise against melanoma Source: Reuters Health eLine Date: April 08, 2002 http://www.reuters.gov/archive/2002/04/08/eline/links/20020408elin 035.html

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Small choroidal melanomas successfully eradicated with cryotherapy Source: Reuters Medical News Date: March 22, 2002 http://www.reuters.gov/archive/2002/03/22/professional/links/20020 322clin005.html

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Viragen says natural alpha interferon may boost relapse-free melanoma survival Source: Reuters Industry Breifing Date: March 20, 2002 http://www.reuters.gov/archive/2002/03/20/business/links/20020320 drgd005.html

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EntreMed's Endostatin gets orphan drug designation for melanoma Source: Reuters Industry Breifing Date: February 28, 2002 http://www.reuters.gov/archive/2002/02/28/business/links/20020228 rglt006.html

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Corixa gets FDA panel backing to test melanoma vaccine against placebo Source: Reuters Industry Breifing Date: February 27, 2002 http://www.reuters.gov/archive/2002/02/27/business/links/20020227 rglt002.html

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Antigenics wins fast-track designation for melanoma vaccine Source: Reuters Industry Breifing Date: February 05, 2002 http://www.reuters.gov/archive/2002/02/05/business/links/20020205 rglt004.html

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Histamine enhances effectiveness of interleukin-2 against melanoma Source: Reuters Industry Breifing Date: January 24, 2002 http://www.reuters.gov/archive/2002/01/24/business/links/20020124 clin011.html

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DNA repair ability affects risk of melanoma: study Source: Reuters Health eLine Date: January 16, 2002 http://www.reuters.gov/archive/2002/01/16/eline/links/20020116elin 008.html

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FDA committee to discuss Corixa's proposed melanoma trial Source: Reuters Industry Breifing Date: January 15, 2002 http://www.reuters.gov/archive/2002/01/15/business/links/20020115 rglt002.html

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Abgenix files IND for melanoma drug candidate Source: Reuters Industry Breifing Date: January 07, 2002 http://www.reuters.gov/archive/2002/01/07/business/links/20020107 rglt002.html

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within their search engine. The following was recently indexed as relating to melanoma: ·

Computer Images Provide Better Melanoma Detection http://www.nlm.nih.gov/medlineplus/news/fullstory_10537.html

Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com. You can scan the news by industry category or company name.

Internet Wire Internet Wire is more focused on technology than the other wires. To access this site, go to http://www.internetwire.com and use the “Search Archive” option. Type in “melanoma” (or synonyms). As this service is oriented to technology, you may wish to search for press releases covering diagnostic procedures or tests that you may have read about.

Search Engines Free-to-view news can also be found in the news section of your favorite search engines (see the health news page at Yahoo:

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http://dir.yahoo.com/Health/News_and_Media/, or use this Web site’s general news search page http://news.yahoo.com/. Type in “melanoma” (or synonyms). If you know the name of a company that is relevant to melanoma, you can go to any stock trading Web site (such as www.etrade.com) and search for the company name there. News items across various news sources are reported on indicated hyperlinks.

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “melanoma” (or synonyms).

Newsletter Articles If you choose not to subscribe to a newsletter, you can nevertheless find references to newsletter articles. We recommend that you use the Combined Health Information Database, while limiting your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” By making these selections, and typing in “melanoma” (or synonyms) into the “For these words:” box, you will only receive results on newsletter articles. You should check back periodically with this database as it is updated every 3 months. The following is a typical result when searching for newsletter articles on melanoma: ·

Skin Cancer: Is Sunscreen and Enabler? Source: Harvard Health Letter. 25(9): 1-3. July 2000. Contact: Available from Harvard Health Letter, P.O. Box 380, Department BI, Boston, MA 02117. (800) 829-9045 or (617) 432-1485. Email: [email protected]. Summary: This newsletter article provides the general public with information on sun exposure and sunscreening agents. Although sunscreening agents stop sunburn by absorbing ultraviolet B (UVB) rays, they do not block other parts of the light spectrum that may have a role in causing skin cancer, particularly melanoma. The use of sunscreens may

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be giving people a false sense of security and enabling the intense, intermittent exposure to sunlight that happens over vacations. Studies on the sunscreen use and melanoma connection have been controversial. However, people should continue to use sunscreens because they do protect against sunburn. Although UVA light was once thought to be a harmless, tan producing part of the light spectrum, it is now known that UVA damages and ages the skin in various ways by initiating a molecular cascade that produces reactive forms of oxygen that damage DNA and cell membranes. UVA may also suppress the immune system. Most sunscreening products now available are broad spectrum and claim to protect against UVB and UVA. Sunscreens are made UVA protective by adding a chemical that absorbs UVA light or adding very finely ground zinc oxide to titanium oxide. However, these broad spectrum sunscreens do not block or absorb all the UVA light. An alternative to sunscreening agents is sun protective clothing. This type of clothing should have a tight weave and be dark. In addition, avoiding sun exposure between 10 a.m. and 4 p.m. may also help protect against skin cancer. ·

Melanoma Vaccine: Breaking the Antigen Packaging Barrier Source: Dermatology Focus. 15(4):1,10-14; April 1997. Contact: Dermatology Foundation, 1560 Sherman Avenue, Evanston, IL 60201-4808. Summary: This newsletter article for health professionals discusses the development of a melanoma vaccine. The creation of a tumor rejection antigen in mice is described. Researchers transfected tumor cells from B16, a poorly immunogenic mouse-derived melanoma, with the ovalbumin (OVA) gene. This modified tumor then treated the foreign OVA deoxyribonucleic acid as its own and began producing the protein. Immunization was performed by two subcutaneous injections one week apart of the OVA protein in particulate form. Results of studies of this immunization process and studies on the loading of dendritic cells in vitro are presented. In addition, in vivo engineering of professional antigen-presenting cells is explained. The applicability of this research is considered.

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Spotting and Curing Skin Cancer Source: Health After 50. 4-6; May 1997. Contact: Johns Hopkins Medical Letter, Health After 50, 550 North Broadway, Suite 1100, Baltimore, MD 21205-2011.

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Summary: This newsletter article for the general public provides guidelines for detecting skin cancers. It presents data on the incidence of skin cancer and describes the characteristics of basal and squamous cell cancer and melanoma. Steps for reducing the risk of skin cancer are outlined, including avoiding the sun during peak intensity; wearing sunglasses, a hat, and tightly woven clothes; and using sunscreen. In addition, the article discusses various methods of treating skin cancer, including curettage and electrodesiccation, conventional surgery, and Mohs' surgery.

Academic Periodicals Covering Melanoma Academic periodicals can be a highly technical yet valuable source of information on melanoma. We have compiled the following list of periodicals known to publish articles relating to melanoma and which are currently indexed within the National Library of Medicine’s PubMed database (follow hyperlinks to view more information, summaries, etc., for each). In addition to these sources, to keep current on articles written on melanoma published by any of the periodicals listed below, you can simply follow the hyperlink indicated or go to the following Web site: www.ncbi.nlm.nih.gov/pubmed. Type the periodical’s name into the search box to find the latest studies published. If you want complete details about the historical contents of a periodical, you can also visit the Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/ you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.” The following is a sample of periodicals which publish articles on melanoma: ·

Acta Dermato-Venereologica. (Acta Derm Venereol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ac ta+Dermato-Venereologica&dispmax=20&dispstart=0

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American Family Physician. (Am Fam Physician) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=A merican+Family+Physician&dispmax=20&dispstart=0

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Biochemical Pharmacology. (Biochem Pharmacol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Bi ochemical+Pharmacology&dispmax=20&dispstart=0

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British Journal of Cancer. (Br J Cancer) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Bri tish+Journal+of+Cancer&dispmax=20&dispstart=0

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Cancer Research. (Cancer Res) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ca ncer+Research&dispmax=20&dispstart=0

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Cell Biology International. (Cell Biol Int) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ce ll+Biology+International&dispmax=20&dispstart=0

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Clinical & Experimental Metastasis. (Clin Exp Metastasis) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Cli nical+&+Experimental+Metastasis&dispmax=20&dispstart=0

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Clinical Chemistry. (Clin Chem) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Cli nical+Chemistry&dispmax=20&dispstart=0

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Clinical Nuclear Medicine. (Clin Nucl Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Cli nical+Nuclear+Medicine&dispmax=20&dispstart=0

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Experimental Dermatology. (Exp Dermatol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ex perimental+Dermatology&dispmax=20&dispstart=0

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Gene Therapy. (Gene Ther) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ge ne+Therapy&dispmax=20&dispstart=0

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Head & Neck. (Head Neck) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=He ad+&+Neck&dispmax=20&dispstart=0

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Journal of Comparative Pathology. (J Comp Pathol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Comparative+Pathology&dispmax=20&dispstart=0

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Journal of Neurosurgery. (J Neurosurg) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Neurosurgery&dispmax=20&dispstart=0

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Lasers in Surgery and Medicine. (Lasers Surg Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=La sers+in+Surgery+and+Medicine&dispmax=20&dispstart=0

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Molecular Medicine (Cambridge, Mass. . (Mol Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=M olecular+Medicine+(Cambridge,+Mass.+&dispmax=20&dispstart=0

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Postgraduate Medicine. (Postgrad Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Po stgraduate+Medicine&dispmax=20&dispstart=0

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Seminars in Oncology. (Semin Oncol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Se minars+in+Oncology&dispmax=20&dispstart=0

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The American Journal of Surgical Pathology. (Am J Surg Pathol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Th e+American+Journal+of+Surgical+Pathology&dispmax=20&dispstart=0

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The Journal of Investigative Dermatology. (J Invest Dermatol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Th e+Journal+of+Investigative+Dermatology&dispmax=20&dispstart=0

Vocabulary Builder Doxorubicin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics. It is an anthracycline. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH]

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Mammary: Pertaining to the mamma, or breast. [EU] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Spotting: A slight discharge of blood via the vagina, especially as a sideeffect of oral contraceptives. [EU]

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CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.

NIH Guidelines For the more common diseases, The National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Cancer Institute (NCI); guidelines available at http://cancernet.nci.nih.gov/pdq/pdq_treatment.shtml

244 Melanoma

In this chapter, we begin by reproducing one such guideline for melanoma:

What Is Melanoma?31 Melanoma is a malignant tumor of melanocytes, cells that are derived from the neural crest. Although most melanomas arise in the skin, they may also arise from mucosal surfaces or at other sites to which neural crest cells migrate. Melanoma occurs predominantly in adults, and more than half of the cases arise in apparently normal areas of the skin. Early signs in a nevus that would suggest malignant change include darker or variable discoloration, itching, an increase in size, or the development of satellites. Ulceration or bleeding are later signs. Melanoma in women occurs more commonly on the extremities and in men on the trunk or head and neck, but it can arise from any site on the skin surface. A biopsy, preferably by local excision, should be performed for any suspicious lesions, and the specimens should be examined by an experienced pathologist to allow for microstaging. Suspicious lesions should never be “shaved off” or cauterized. Studies show that distinguishing between benign pigmented lesions and early melanomas can be difficult, and even experienced dermatopathologists can have differing opinions. To reduce the possibility of misdiagnosis for an individual patient, a second review by an independent qualified pathologist should be considered.32 Prognosis is affected by clinical and histological factors and by anatomic location of the lesion. Thickness and/or level of invasion of the melanoma, mitotic index, presence of tumor infiltrating lymphocytes, number of regional lymph nodes involved, and ulceration or bleeding at the primary site affect the prognosis.33 Microscopic satellites in stage I melanoma may be The following guidelines appeared on the NCI website on Aug. 26, 2002. The text was last modified in July 2002. The text has been adapted for this sourcebook. Note: Separate PDQ summaries on Skin Cancer Treatment; Prevention of Skin Cancer; and Screening for Skin Cancer are also available. 32 Corona R, Mele A, Amini M, et al.: Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions. Journal of Clinical Oncology 14(4): 1218-1223, 1996. 33 Balch CM, Soong S, Ross MI, et al.: Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Annals of Surgical Oncology 7(2): 87-97, 2000. Manola J, Atkins M, Ibrahim J, et al.: Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials. Journal of Clinical Oncology 18(22): 3782-3793, 2000. Balch CM, Buzaid AC, Soong SJ, et al.: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. Journal of Clinical Oncology 19(16): 36353648, 2001. 31

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a poor prognostic histologic factor, but this is controversial.34 Patients who are younger, female, and who have melanomas on the extremities generally have a better prognosis.35 Clinical staging is based on whether the tumor has spread to regional lymph nodes or distant sites. For disease clinically confined to the primary site, the greater the thickness and depth of local invasion of the melanoma, the higher the chance of lymph node or systemic metastases and the worse the prognosis. Melanoma can spread by local extension (through lymphatics) and/or by hematogenous routes to distant sites. Any organ may be involved by metastases, but lungs and liver are common sites. The risk of relapse decreases substantially over time, although late relapses are not uncommon.36

Cellular Classification Following is a list of clinicopathologic cellular subtypes of malignant melanoma. These should be considered descriptive terms of historic interest only as they do not have independent prognostic or therapeutic significance. ·

Superficial spreading

·

Nodular

Lotze MT: Melanoma. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott Williams & Wilkins, 6th ed., 2001, pp. 2022-2028. 34 Leon P, Daly JM, Synnestvedt M, et al.: The prognostic implications of microscopic satellites in patients with clinical stage I melanoma. Archives of Surgery 126(12): 1461-1468, 1991. 35 Balch CM, Soong S, Ross MI, et al.: Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Annals of Surgical Oncology 7(2): 87-97, 2000. Manola J, Atkins M, Ibrahim J, et al.: Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials. Journal of Clinical Oncology 18(22): 3782-3793, 2000. Balch CM, Buzaid AC, Soong SJ, et al.: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. Journal of Clinical Oncology 19(16): 36353648, 2001. Lotze MT: Melanoma. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott Williams & Wilkins, 6th ed., 2001, pp. 2022-2028. 36 Shen P, Guenther JM, Wanek LA, et al.: Can elective lymph node dissection decrease the frequency and mortality rate of late melanoma recurrences? Annals of Surgical Oncology 7(2): 114-119, 2000. Tsao H, Cosimi AB, Sober AJ: Ultra-late recurrence (15 years or longer) of cutaneous melanoma. Cancer 79(12): 2361-2370, 1997.

246 Melanoma

·

Lentigo maligna

·

Acral lentiginous (palmar/plantar and subungual)

·

Miscellaneous unusual types: -

Mucosal lentiginous (oral and genital)

-

Desmoplastic

-

Verrucous

Stage Information Agreement between pathologists in the histologic diagnosis of melanomas and benign pigmentented lesions has been studied and found to be considerably variable. One such study found that there was discordance on the diagnosis of melanoma versus benign lesions in 37 of 140 cases examined by a panel of experienced dermatopathologists.37 For the histologic classification of cutaneous melanoma, the highest concordance was attained for Breslow thickness and presence of ulceration, while the agreement was poor for other histologic features such as Clark’s level of invasion, presence of regression, and lymphocytic infiltration. In another study, 38% of cases examined by a panel of expert pathologists had 2 or more discordant interpretations. These studies convincingly show that distinguishing between benign pigmented lesions and early melanoma can be difficult, and even experienced dermatopathologists can have differing opinions. To reduce the possibility of misdiagnosis for an individual patient, a second review by an independent qualified pathologist should be considered.38 The microstage of malignant melanoma is determined on histologic examination by the vertical thickness of the lesion in millimeters (Breslow’s classification) and/or the anatomic level of local invasion (Clark’s classification). The Breslow thickness is more reproducible and more accurately predicts subsequent behavior of malignant melanoma in lesions greater than 1.5 millimeters in thickness and should always be reported. Accurate microstaging of the primary tumor requires careful histologic evaluation of the entire specimen by an experienced pathologist. Estimates of

Corona R, Mele A, Amini M, et al.: Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions. Journal of Clinical Oncology 14(4): 1218-1223, 1996. 38 Farmer ER, Gonin R, Hanna MP: Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Human Pathology 27(6): 528531, 1996. 37

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prognosis should be modified by sex and anatomic site as well as by clinical and histologic evaluation.

Clark’s Classification (Level of Invasion) ·

Level I: lesions involving only the epidermis (in situ melanoma); not an invasive lesion

·

Level II: invasion of the papillary dermis, but does not reach the papillary-reticular dermal interface

·

Level III: invasion fills and expands the papillary dermis, but does not penetrate the reticular dermis

·

Level IV: invasion into the reticular dermis but not into the subcutaneous tissue

·

Level V: invasion through the reticular dermis into the subcutaneous tissue

·

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define melanoma.39

TNM Definitions Primary Tumor (T) ·

T0: Melanoma in situ

·

Tis: (atypical melanocytic hyperplasia, severe melanocytic dysplasia), not an invasive lesion (Clark’s Level I)

·

T1: Tumor 1.0 mm or less in thickness

·

·

-

T1a: without ulceration and Clark’s level II or III

-

T1b: with ulceration, or Clark’s level IV or V

T2: Tumor more than 1.0 mm, but not more than 2.0 mm in thickness -

T2a: without ulceration

-

T2b: with ulceration

T3: Tumor more than 2.0 mm but not more than 4 mm in thickness -

T3a: without ulceration

Balch CM, Buzaid AC, Soong SJ, et al.: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. Journal of Clinical Oncology 19(16): 36353648, 2001.

39

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·

T3b: with ulceration

T4: Tumor more than 4.0 mm in thickness -

T4a: without ulceration

-

T4b: with ulceration

Regional Lymph Nodes (N) ·

N0: No regional lymph node metastasis

·

N1: Metastasis to 1 lymph node

·

·

-

N1a: micrometastasis

-

N1b: macrometastasis

N2: Metastasis to 2 or 3 lymph nodes -

N2a: micrometastasis

-

N2b: macrometastasis

-

N2c: in-transit metastasis or satellite(s) without lymph node metastasis

N3: 4 or more metastatic lymph nodes, or matted lymph nodes, or intransit metastasis or satellites with metastatic lymph nodes

Note: Micrometastases are diagnosed after elective or sentinel lymphadenectomy; macrometastases are defined as clinically detectable lymph nodes metastases confirmed by therapeutic lymphadenectomy, or when any lymph node metastasis exhibits gross extracapsular extension.

Distant Metastasis (M) ·

M1a: Distant skin, subcutaneous, or lymph node metastases with normal serum LDH

·

M1b: Lung metastasis with normal serum LDH

·

M1c: All other visceral metastases with normal serum LDH, or any distant metastases with elevated serum LDH

Clinical Staging Clinical staging includes microstaging of the primary melanoma and clinical and/or radiologic evaluation for regional and/or distant metastases. By

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convention, it should be assigned after complete excision and pathologic assessment of the primary melanoma with clinical assessment for regional and distant metastases.40 AJCC Groupings Stage 0: ·

Tis, N0, M0

Stage IA: ·

T1a, N0, M0

Stage IB: ·

T1b, N0, M0

·

T2a, N0, M0

Stage IIA: ·

T2b, N0, M0

·

T3a, N0, M0

Stage IIB: ·

T3b, N0, M0

·

T4a, N0, M0

Stage IIC: ·

T4b, N0, M0

Stage III: ·

Any T, any N, M0

Stage IV: Balch CM, Buzaid AC, Soong SJ, et al.: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. Journal of Clinical Oncology 19(16): 36353648, 2001.

40

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·

Any T, any N, any M

Pathologic Staging With the exception of clinical stage 0 or stage IA patients (who have a low risk of lymphatic involvement and do not require pathologic evaluation of their lymph nodes), pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after sentinel node biopsy and, if indicated, complete lymphadenectomy.41

AJCC Groupings Stage 0: ·

Tis, N0, M0

Stage IA: ·

T1a, N0, M0

Stage IB: ·

T1b, N0, M0

·

T2a, N0, M0

Stage IIA: ·

T2b, N0, M0

·

T3a, N0, M0

Stage IIB: ·

T3b, N0, M0

·

T4a, N0, M0

Balch CM, Buzaid AC, Soong SJ, et al.: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. Journal of Clinical Oncology 19(16): 36353648, 2001.

41

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Stage IIC: ·

T4b, N0, M0

Stage IIIA: ·

T1-4a, N1a, M0

·

T1-4a, N2a, M0

Stage IIIB: ·

T1-4b, N1a, M0

·

T1-4b, N2a, M0

·

T1-4a, N1b, M0

·

T1-4a, N2b, M0

·

T1-4a, N2c, M0

Stage IIIC: ·

T1-4b, N1b, M0

·

T1-4b, N2b, M0

·

T1-4b, N2c, M0

·

Any T, N3, M0

Stage IV: ·

Any T, any N, any M

Treatment Option Overview42 Melanomas that have not spread beyond the site at which they developed are highly curable. Most of these are thin lesions that have not invaded beyond the papillary dermis (Clark’s level I-II; Breslow thickness 1.0 millimeter or less). The treatment of localized melanoma is surgical excision with margins proportional to the microstage of the primary lesion; for most Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

42

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thin (low-risk) lesions, this means 1.0 centimeter radical re-excision margins.43 Melanomas with a Breslow thickness greater than 1.0 millimeter are still curable in a significant proportion of patients, but the risk of lymph node and/or systemic metastasis increases with increasing thickness of the primary lesion. The local treatment for these melanomas is surgical excision with margins based on Breslow thickness and anatomic location. For most melanomas 1 to 4 millimeters thick, this means 2.0 centimeter radial excision margins, and for melanomas greater than 4 millimeters thick, 2 to 3 centimeter radial margins. These patients should also be considered for sentinel lymph node biopsy followed by complete lymph node dissection if the sentinel node(s) are microscopically or macroscopically positive. Sentinel node biopsy should be performed prior to wide excision of the primary melanoma to insure accurate lymphatic mapping. Patients with melanomas that have a Breslow thickness greater than 4 millimeters should be considered for adjuvant therapy with high-dose interferon. Some melanomas that have spread to regional lymph nodes may be curable with wide local excision of the primary tumor and removal of the involved regional lymph nodes.44 In a prospective, randomized controlled trial, adjuvant high-dose interferon was shown to increase relapse-free and overall survival when compared to observation.45 A subsequent randomized trial conducted by the same group of investigators using the same high-dose interferon regimen confirmed the relapse-free but not the overall survival

Veronesi U, Cascinelli N: Narrow excision (1-cm margin): a safe procedure for thin cutaneous melanoma. Archives of Surgery 126(4): 438-441, 1991. Veronesi U, Cascinelli N, Adamus J, et al.: Thin stage I primary cutaneous malignant melanoma: comparison of excision with margins of 1 or 3 cm. New England Journal of Medicine 318(18): 1159-1162, 1988. 44 Shen P, Wanek LA, Morton DL: Is adjuvant radiotherapy necessary after positive lymph node dissection in head and neck melanomas? Annals of Surgical Oncology 7(8): 554-559, 2000. Hochwald SN, Coit DG: Role of elective lymph node dissection in melanoma. Seminars in Surgical Oncology 14(4): 276-282, 1998. Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. Cascinelli N, Morabito A, Santinami M, et al.: Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. Lancet 351(9105): 793796, 1998. 45 Kirkwood JM, Strawderman MH, Ernstoff MS, et al.: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group trial EST 1684. Journal of Clinical Oncology 14(1): 7-17, 1996. 43

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advantage.46 A third randomized trial again demonstrated both a diseasefree and overall survival advantage to high-dose interferon when compared to a ganglioside vaccine.47 Clinicians should be aware that high-dose interferon regimens have substantial side effects, and patients should be monitored closely. Adjuvant chemotherapy does not improve survival. A multicenter phase III randomized trial of patients with high-risk primary limb melanoma did not show a benefit from isolated limb perfusion with melphalan in regard to disease-free survival or overall survival when compared to surgery alone.48 Melanoma that has spread to distant sites is rarely curable with standard therapy, although high-dose interleukin-2 (IL-2) has been reported to produce durable responses in a small number of patients.49 In patients with systemic metastasis confined to 1 anatomic site, long-term survival is occasionally achieved by complete resection of all metastatic disease.50 All patients with distant metastasis are appropriately considered candidates for clinical trials exploring new forms of treatment, including combination chemotherapy, biological response modifiers (such as specific monoclonal antibodies, interferons, IL-2, or tumor necrosis factor-alfa), vaccine immunotherapy, or biochemotherapy (chemoimmunotherapy).

Kirkwood JM, Ibrahim JG, Sondak VK, et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. Journal of Clinical Oncology 18(12): 2444-2458, 2000. 47 Kirkwood JM, Ibrahim J, Lawson DH, et al.: High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the multicenter Eastern Cooperative Oncology Group phase II trial E2696. Journal of Clinical Oncology 19(5): 1430-1436, 2001. 48 Koops HS, Vaglini M, Suciu S, et al.: Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. Journal of Clinical Oncology 16(9): 2906-2912, 1998. 49 Atkins MB, Lotze MT, Dutcher JP, et al.: High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. Journal of Clinical Oncology 17(7): 2105-2116, 1999. Atkins MB, Kunkel L, Sznol M, et al.: High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer Journal from Scientific American 6(suppl 1): S11-S14, 2000. 50 Lee ML, Tomsu K, von Eschen KB: Duration of survival for disseminated malignant melanoma: results of a meta-analysis. Melanoma Research 10(1): 81-92, 2000. Leo F, Cagini L, Rocmans P, et al.: Lung metastases from melanoma: when is surgical treatment warranted? British Journal of Cancer 83(5): 569-572, 2000. Ollila DW, Hsueh EC, Stern SL, et al.: Metastasectomy for recurrent stage IV melanoma. Journal of Surgical Oncology 71(4): 209-213, 1999. Gutman H, Hess KR, Kokotsakis JA, et al.: Surgery for abdominal metastases of cutaneous melanoma. World Journal of Surgery 25(6): 750-758, 2001. 46

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Malignant melanoma has been reported to spontaneously regress, however the incidence of spontaneous complete regressions is less than 1%.51 Patients with all stages of melanoma may be considered candidates for ongoing clinical trials. The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.

Stage 0 Melanoma Patients with stage 0 disease may be treated by excision with minimal, but microscopically-free, margins.

Stage I Melanoma Standard treatment options: ·

T1 lesions may be treated conservatively with radical excision margins of 1 centimeter.52 Patients with T2 lesions may require wider surgical excision of the primary tumor. Two randomized trials have demonstrated that, for melanomas of intermediate thickness (> 0.75-4.0 millimeters), the surgical margins need to be no greater than 2 centimeters.53 These trials compared 2 centimeter margins with wider margins (i.e., 4 or 5 centimeters), and no statistically significant differences were found in local recurrence, distant metastasis, or overall survival, with a median follow-up of 10 years or more for both trials. The reduction in margins

Wang TS, Lowe L, Smith JW 2nd, et al.: Complete spontaneous regression of pulmonary metastatic melanoma. Dermatologic Surgery 24(8): 915-919, 1998. 52 Veronesi U, Cascinelli N: Narrow excision (1-cm margin): a safe procedure for thin cutaneous melanoma. Archives of Surgery 126(4): 438-441, 1991. Veronesi U, Cascinelli N, Adamus J, et al.: Thin stage I primary cutaneous malignant melanoma: comparison of excision with margins of 1 or 3 cm. New England Journal of Medicine 318(18): 1159-1162, 1988. 53 Cohn-Cedermark G, Rutqvist LE, Andersson R, et al.: Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm. Cancer 89(7): 1495-1501, 2000. Balch CM, Soong SJ, Smith T, et al.: Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas. Annals of Surgical Oncology 8(2): 101-108, 2001. Balch CM, Urist MM, Karakousis CP, et al.: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm): results of a multi-institutional randomized surgical trial. Annals of Surgery 218(3): 262-269, 1993. 51

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from 4 centimeters to 2 centimeters was associated with a statistically significant reduction in the need for skin grafting (from 46% to 11%, p<.001) and a reduction in the length of the hospital stay.54 Depending on the location of the melanoma, most patients can now have this procedure performed on an outpatient basis. ·

Elective regional lymph node dissection is of no proven benefit for patients with stage I melanoma. However, lymphatic mapping and sentinel lymph node biopsy for patients who have tumors of intermediate thickness and/or have ulcerated may allow the identification of individuals with occult nodal disease who might benefit from regional lymphadenectomy and adjuvant therapy.55 Results are pending from a multicenter randomized trial that is comparing wide local excision alone to wide local excision plus intraoperative lymphatic mapping and selective lymphadenectomy in patients with clinically negative lymph nodes.56

Treatment options under clinical evaluation: ·

Because of the higher rate of treatment failure in the subset of clinical stage I patients with occult nodal disease, clinical trials are evaluating new techniques to detect submicroscopic sentinel lymph node metastasis, in order to identify those patients who may benefit from regional lymphadenectomy with or without adjuvant therapy. One of the objectives of the currently ongoing phase III “Sunbelt Melanoma Trial” is to determine the effects of lymphadenectomy with or without adjuvant high-dose interferon alfa-2b versus observation on disease-free and overall survival in patients with submicroscopic sentinel lymph node

Balch CM, Urist MM, Karakousis CP, et al.: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm): results of a multi-institutional randomized surgical trial. Annals of Surgery 218(3): 262-269, 1993. 55 Hochwald SN, Coit DG: Role of elective lymph node dissection in melanoma. Seminars in Surgical Oncology 14(4): 276-282, 1998. Essner R, Conforti A, Kelley MC, et al.: Efficacy of lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection as a therapeutic procedure for early-stage melanoma. Annals of Surgical Oncology 6(5): 442-449, 1999. Gershenwald JE, Thompson W, Mansfield PF, et al.: Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. Journal of Clinical Oncology 17(3): 976-983, 1999. Mraz-Gernhard S, Sagebiel RW, Kashani-Sabet M, et al.: Prediction of sentinel lymph node micrometastasis by histological features in primary cutaneous malignant melanoma. Archives of Dermatology 134(8): 983-987, 1998. 56 Roses DF, NYU School of Medicine’s Kaplan Comprehensive Cancer Center, NYUMC: Randomized Study of Wide Excision Versus Wide Excision Plus Intraoperative Lymphatic Mapping and Selective Lymphadenectomy in Patients with Invasive Cutaneous Melanoma (Summary Last Modified 01/2000), NYU-9348, clinical trial, closed, 06/04/1998. 54

256 Melanoma

metastasis detected only by the polymerase chain reaction (PCR) (i.e., sentinel lymph node negative by histology and immunohistochemistry).57 No survival data have been reported from this study. An ongoing diagnostic study is testing the combination of reverse transcription and PCR (RT-PCR) in the detection of melanoma tumor antigen transcripts in lymph nodes and peripheral blood samples.58

Stage II Melanoma Standard treatment options: ·

Two randomized trials have demonstrated that, for melanomas of intermediate thickness (> 0.75-4.0 millimeters), the surgical margins need to be no greater than 2 centimeters.59 These trials compared 2 centimeter margins with wider margins (i.e., 4 or 5 centimeters), and no statistically significant differences were found in local recurrence, distant metastasis, or overall survival, with a median follow-up of 10 years or more for both trials. The reduction in margins from 4 centimeters to 2 centimeters was associated with a statistically significant reduction in the need for skin grafting (from 46% to 11%, p<.001) and a reduction in the length of the hospital stay.60 Depending on the location of the melanoma, most patients can now have this surgery performed on an outpatient basis.

Urist MM, University of Alabama at Birmingham Comprehensive Cancer Center: Phase III Study of Adjuvant Interferon alfa-2b in Patients With Invasive Cutaneous Melanoma With Early Lymph Node Metastasis Detected By Intraoperative Lymphatic Mapping and Sentinel Lymph Node Biopsy (Summary Last Modified 10/2001), UAB-9735, clinical trial, active, 08/24/2001. 58 Gajewski TF, University of Chicago Cancer Research Center: Diagnostic Study of Reverse Transcriptase-Polymerase Chain Reaction to Detect Melanoma Markers in Lymph Nodes or Peripheral Blood of Patients With Melanoma (Summary Last Modified 06/2000), UCCRC9308, clinical trial, active, 06/01/1998. 59 Cohn-Cedermark G, Rutqvist LE, Andersson R, et al.: Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm. Cancer 89(7): 1495-1501, 2000. Balch CM, Soong SJ, Smith T, et al.: Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas. Annals of Surgical Oncology 8(2): 101-108, 2001. Balch CM, Urist MM, Karakousis CP, et al.: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm): results of a multi-institutional randomized surgical trial. Annals of Surgery 218(3): 262-269, 1993. 60 Balch CM, Urist MM, Karakousis CP, et al.: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm): results of a multi-institutional randomized surgical trial. Annals of Surgery 218(3): 262-269, 1993. 57

Physician Guidelines and Databases 257

·

Although prophylactic regional lymph node dissections have been used in patients with stage II melanomas, 4 prospective randomized trials have failed to show a benefit for this procedure in terms of survival.61

·

Lymphatic mapping and sentinel lymph node biopsy have been used to assess the presence of occult metastasis in the regional lymph nodes of patients with stage II disease, potentially identifying individuals who may be spared the morbidity of regional lymph node dissection and individuals who may benefit from adjuvant therapy.62 The diagnostic accuracy of sentinel lymph node biopsy has been demonstrated in several studies, with a false-negative rate of 0% to 2%.63 Using a vital blue dye

Veronesi U, Adamus J, Bandiera DC, et al.: Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities. Cancer 49(11): 2420-2430, 1982. Sim FH, Taylor WF, Ivins JC, et al.: A prospective randomized study of the efficacy of routine elective lymphadenectomy in management of malignant melanoma: preliminary results. Cancer 41(3): 948-956, 1978. Balch CM, Soong SJ, Bartolucci AA, et al.: Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Annals of Surgery 224(3): 255-266, 1996. Cascinelli N, Morabito A, Santinami M, et al.: Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. Lancet 351(9105): 793796, 1998. 62 Gershenwald JE, Thompson W, Mansfield PF, et al.: Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. Journal of Clinical Oncology 17(3): 976-983, 1999. McMasters KM, Reintgen DS, Ross MI, et al.: Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement. Journal of Clinical Oncology 19(11): 2851-2855, 2001. Cherpelis BS, Haddad F, Messina J, et al.: Sentinel lymph node micrometastasis and other histologic factors that predict outcome in patients with thicker melanomas. Journal of the American Academy of Dermatology 44(5): 762-766, 2001. Essner R: The role of lymphoscintigraphy and sentinel node mapping in assessing patient risk in melanoma. Seminars in Oncology 24(1 suppl 4): S8-S10, 1997. Chan AD, Morton DL: Sentinel node dissection in malignant melanoma. Recent Results in Cancer Research 157: 161-177, 2000. 63 Gershenwald JE, Thompson W, Mansfield PF, et al.: Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. Journal of Clinical Oncology 17(3): 976-983, 1999. Morton DL, Wen DR, Wong JH, et al.: Technical details of intraoperative lymphatic mapping for early stage melanoma. Archives of Surgery 127(4): 392-399, 1992. Reintgen D, Cruse CW, Wells K, et al.: The orderly progression of melanoma nodal metastases. Annals of Surgery 220(6): 759-767, 1994. Thompson JF, McCarthy WH, Bosch CM, et al.: Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Research 5(4): 255-260, 1995. Uren RF, Howman-Giles R, Thompson JF, et al.: Lymphoscintigraphy to identify sentinel lymph nodes in patients with melanoma. Melanoma Research 4(6): 395-399, 1994. 61

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and a radiopharmaceutical agent, which are injected at the site of the primary tumor, the first lymph node in the lymphatic basin that drains the lesion can be identified, removed, and examined microscopically. If metastatic melanoma is detected, a complete regional lymphadenectomy can then be performed in a second procedure. To insure accurate identification of the sentinel lymph node, lymphatic mapping and removal of the sentinel lymph node should be performed prior to wide excision of the primary melanoma. ·

To date, there are no published data from prospective trials on the clinical significance of micrometastatic melanoma in regional lymph nodes, but some evidence suggests that, for patients with tumors of intermediate thickness and occult metastasis, survival is better among those patients who undergo immediate regional lymphadenectomy than among those who delay lymphadenectomy until the clinical appearance of nodal metastasis.64 Because this finding arose from a post-hoc subset analysis of data from a randomized trial, it should be viewed with caution. Results are pending from a multicenter, randomized trial that is comparing wide local excision alone to wide local excision plus intraoperative lymphatic mapping and selective lymphadenectomy in patients with clinically negative lymph nodes.65

·

A retrospective matched-pair analysis of 534 patients found equivalent 5year overall survival rates for lymphatic mapping, sentinel lymph node biopsy, and regional lymphadenectomy in sentinel node-positive patients versus elective lymph node dissection, but lymphatic mapping and sentinel lymph node biopsy was more effective in identifying occult nodal metastasis in patients with tumors of intermediate thickness.66

Adjuvant therapy: ·

A multicenter randomized controlled study has compared a high-dose regimen of interferon alfa-2b (20 million units per square meter of body

Bostick P, Essner R, Glass E, et al.: Comparison of blue dye and probe-assisted intraoperative lymphatic mapping in melanoma to identify sentinel nodes in 100 lymphatic basins. Archives of Surgery 134(1): 43-49, 1999. 64 Cascinelli N, Morabito A, Santinami M, et al.: Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. Lancet 351(9105): 793796, 1998. 65 Roses DF, NYU School of Medicine’s Kaplan Comprehensive Cancer Center, NYUMC: Randomized Study of Wide Excision Versus Wide Excision Plus Intraoperative Lymphatic Mapping and Selective Lymphadenectomy in Patients with Invasive Cutaneous Melanoma (Summary Last Modified 01/2000), NYU-9348, clinical trial, closed, 06/04/1998. 66 Essner R, Conforti A, Kelley MC, et al.: Efficacy of lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection as a therapeutic procedure for early-stage melanoma. Annals of Surgical Oncology 6(5): 442-449, 1999.

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surface per day given intravenously for 5 days a week for 4 weeks, then 10 million units per square meter of body surface per day given subcutaneously 3 times a week for 48 weeks) to observation.67 This study included 287 patients at high risk for recurrence after potentially curative surgery for melanoma (patients with melanoma >4 millimeters thick without involved lymph nodes, or patients with melanomas of any thickness with positive lymph nodes). Patients who had recurrent melanoma only involving the regional lymph nodes were also eligible. At a median follow-up of 7 years, this trial demonstrated a significant prolongation of relapse-free (p=.0023) and overall survival (p=.0237) for patients receiving high-dose interferon. ·

The overall median survival for patients who received the high-dose regimen of interferon alfa-2b was 3.8 years compared with 2.8 years for those in the observation group.68 [Level of evidence: 1iiA] However, a subset analysis of the stage II patients failed to show any benefit from high-dose interferon in terms of relapse-free or overall survival. Because the number of stage II patients was small in this subset analysis, it is difficult to draw meaningful conclusions from this study for this specific group.

·

A subsequent multicenter randomized controlled study by the same investigators compared the same high-dose regimen of interferon alfa to either a lower dose regimen (3 million units per day given subcutaneously 3 times a week every week for 104 weeks) or observation.69 The stage entry criteria for this trial were the same as for the initial study. This 3-arm trial entered 642 patients. At a median follow-up of 52 months, a statistically significant relapse-free survival advantage was shown for all patients who received high-dose interferon (including the clinical stage II patients) when compared with the observation group (p=0.03), however there was no statistically significant relapse-free survival advantage for low-dose interferon when compared to the observation group. The 5-year estimated relapse-free survival rates for the high-dose interferon, low-dose interferon, and observation groups were 44%, 40%, and 35%, respectively. Neither high-dose nor low-dose

Kirkwood JM, Strawderman MH, Ernstoff MS, et al.: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group trial EST 1684. Journal of Clinical Oncology 14(1): 7-17, 1996. 68 Kirkwood JM, Strawderman MH, Ernstoff MS, et al.: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group trial EST 1684. Journal of Clinical Oncology 14(1): 7-17, 1996. 69 Kirkwood JM, Ibrahim JG, Sondak VK, et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. Journal of Clinical Oncology 18(12): 2444-2458, 2000. 67

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interferon yielded an overall survival benefit when compared to observation (hazard ratio [HR]=1.0, p=0.995).70 [Level of evidence: 1iiA] ·

Another multicenter prospective trial randomized patients with resected stage IIB or III melanoma to receive either the same high-dose interferonalfa-2b regimen or a vaccine of conjugated GM2 melanoma antigen (GM2-KLH/QS-21).71 Eight hundred eighty patients were randomized, and 774 were eligible for efficacy analysis. This trial was closed after an interim evaluation indicated the inferiority of the GMK vaccine compared to treatment with interferon. A statistically significant relapsefree survival was found for high-dose interferon (HR=1.47, p=0.0015), as was a statistically significant overall survival benefit (HR=1.52, p=.009). (In the intent-to-treat analysis, relapse-free survival HR=1.49; overall survival HR=1.38.) For the population eligible for efficacy analysis, the greatest benefit was seen in the node-negative (stage IIB) subset (relapsefree survival HR=2.07; overall survival HR=2.71).72 [Level of evidence: 1iiA]

·

Clinicians should be aware that the high dose regimens have substantial side effects and patients must be monitored closely.

Treatment options under clinical evaluation: ·

Because of the higher rate of treatment failure in this group, clinical trials exploring adjuvant chemotherapy and/or biologic therapy, or immunotherapy, are appropriate choices when possible for newly diagnosed patients. Other clinical trials are evaluating new techniques to detect submicroscopic sentinel lymph node metastasis, in order to identify those patients who may benefit from regional lymphadenectomy with or without adjuvant therapy. One of the objectives of the ongoing phase III “Sunbelt Melanoma Trial” is to determine the effects of lymphadenectomy with or without adjuvant high-dose interferon alfa-2b versus observation on disease-free and overall survival in patients with submicroscopic sentinel lymph node metastasis detected only by the

Kirkwood JM, Ibrahim JG, Sondak VK, et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. Journal of Clinical Oncology 18(12): 2444-2458, 2000. 71 Kirkwood JM, Ibrahim JG, Sosmam JA, et al.: High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIb-III melanoma: results of Intergroup trial E1694/S9512/C509801. Journal of Clinical Oncology 19(9): 2370-2380, 2001. 72 Kirkwood JM, Ibrahim JG, Sosmam JA, et al.: High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIb-III melanoma: results of Intergroup trial E1694/S9512/C509801. Journal of Clinical Oncology 19(9): 2370-2380, 2001. 70

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polymerase chain reaction (PCR) (i.e., sentinel lymph node negative by histology and immunohistochemistry).73 No survival data have been reported from this study. An ongoing diagnostic study is testing the combination of reverse transcription and PCR (RT-PCR) in the detection of melanoma tumor antigen transcripts in lymph nodes and peripheral blood samples.74 ·

An ongoing phase III trial is evaluating the effect of 1 month of high-dose adjuvant interferon alfa-2b versus observation on relapse-free and overall survival in patients with melanomas greater than 1.5 millimeters in thickness, with or without a single microscopically positive lymph node.75 Results are pending from another phase III study that randomized patients with stage II or III disease to adjuvant intermediate high-dose interferon alfa-2b versus intermediate low-dose interferon alfa-2b versus observation.76

·

Autologous bone marrow transplantation with high-dose chemotherapy has not been shown to improve survival.77

Urist MM, University of Alabama at Birmingham Comprehensive Cancer Center: Phase III Study of Adjuvant Interferon alfa-2b in Patients With Invasive Cutaneous Melanoma With Early Lymph Node Metastasis Detected By Intraoperative Lymphatic Mapping and Sentinel Lymph Node Biopsy (Summary Last Modified 10/2001), UAB-9735, clinical trial, active, 08/24/2001. 74 Gajewski TF, University of Chicago Cancer Research Center: Diagnostic Study of Reverse Transcriptase-Polymerase Chain Reaction to Detect Melanoma Markers in Lymph Nodes or Peripheral Blood of Patients With Melanoma (Summary Last Modified 06/2000), UCCRC9308, clinical trial, active, 06/01/1998. 75 Agarwala S, Eastern Cooperative Oncology Group: Phase III Randomized Adjuvant Study of High Dose Interferon Alfa-2b Therapy in Patients With Stage II and III Melanoma (Summary Last Modified 07/2000), E-1697, clinical trial, active, 12/22/1998. 76 Eggermont AM, EORTC Melanoma Group: Phase III Randomized Study of Adjuvant Intermediate High-Dose IFN-A vs Intermediate Low-Dose IFN-A vs Observation Following Definitive Resection of Thick Primary and/or Regional Lymph Node Metastases in HighRisk Stage III Melanoma (Summary Last Modified 08/2000), EORTC-18952, clinical trial, closed, 06/15/2000. 77 Meisenberg BR, Ross M, Vredenburgh JJ, et al.: Randomized trial of high-dose chemotherapy with autologous bone marrow support as adjuvant therapy for high-risk, multi-node-positive malignant melanoma. Journal of the National Cancer Institute 85(13): 1080-1085, 1993. 73

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Stage III Melanoma Standard treatment options: ·

Wide local excision of the primary tumor with 1 centimeter to 3 centimeter margins, depending on tumor depth and location.78 Skin grafting may be necessary to close the resulting defect.

·

A multicenter, randomized controlled study has compared a high-dose regimen of interferon alfa-2b (20 million units per square meter of body surface per day given intravenously for 5 days a week for 4 weeks, then 10 million units per square meter of body surface per day given subcutaneously 3 times a week for 48 weeks) to observation.79 This study included 287 patients at high risk for recurrence after potentially curative surgery for melanoma (patients with melanoma >4 millimeters thick without involved lymph nodes, or patients with melanomas of any thickness with positive lymph nodes). Patients who had recurrent melanoma only involving the regional lymph nodes were also eligible. At a median follow-up of 7 years, this trial demonstrated a significant prolongation of relapse-free (p=.0023) and overall survival (p=.0237) for patients receiving high-dose interferon.

·

The overall median survival for patients who received the high-dose regimen of interferon alfa-2b was 3.8 years compared with 2.8 years for

Veronesi U, Cascinelli N: Narrow excision (1-cm margin): a safe procedure for thin cutaneous melanoma. Archives of Surgery 126(4): 438-441, 1991. Veronesi U, Cascinelli N, Adamus J, et al.: Thin stage I primary cutaneous malignant melanoma: comparison of excision with margins of 1 or 3 cm. New England Journal of Medicine 318(18): 1159-1162, 1988. Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. Cohn-Cedermark G, Rutqvist LE, Andersson R, et al.: Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm. Cancer 89(7): 1495-1501, 2000. Balch CM, Soong SJ, Smith T, et al.: Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas. Annals of Surgical Oncology 8(2): 101-108, 2001. Heaton KM, Sussman JJ, Gershenwald JE, et al.: Surgical margins and prognostic factors in patients with thick (>4 mm) primary melanoma. Annals of Surgical Oncology 5(4): 322328, 1998. Balch CM, Urist MM, Karakousis CP, et al.: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm): results of a multi-institutional randomized surgical trial. Annals of Surgery 218(3): 262-269, 1993. 79 Kirkwood JM, Strawderman MH, Ernstoff MS, et al.: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group trial EST 1684. Journal of Clinical Oncology 14(1): 7-17, 1996. 78

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those in the observation group.80 [Level of evidence: 1iiA] However, a subset analysis of the stage II patients failed to show any benefit from high-dose interferon in terms of relapse-free or overall survival. Because the number of stage II patients was small in this subset analysis, it is difficult to draw meaningful conclusions from this study for this specific group. ·

A subsequent multicenter randomized controlled study by the same investigators compared the same high-dose regimen of interferon alfa to either a lower dose regimen (3 million units per day given subcutaneously 3 times a week every week for 104 weeks) or observation.81 The stage entry criteria for this trial were the same as for the initial study. This 3-arm trial entered 642 patients. At a median follow-up of 52 months, a statistically significant relapse-free survival advantage was shown for all patients who received high-dose interferon (including the clinical stage II patients) when compared with the observation group (p=0.03), however there was no statistically significant relapse-free survival advantage for low-dose interferon when compared to the observation group. The 5-year estimated relapse-free survival rates for the high-dose interferon, low-dose interferon, and observation groups were 44%, 40%, and 35%, respectively. Neither high-dose nor low-dose interferon yielded an overall survival benefit when compared to observation (hazard ratio [HR]=1.0, p=0.995).82 [Level of evidence: 1iiA]

·

Pooled analyses of the 2 high-dose arms versus the 2 observation arms from both studies suggest that treatment confers a significant relapse-free survival advantage, but not a significant benefit for survival.83 [Level of evidence: 1iiA]

·

Another multicenter, prospective trial randomized patients with resected stage IIB or III melanoma to receive either the same high-dose interferonalfa-2b regimen or a vaccine of conjugated GM2 melanoma antigen

Kirkwood JM, Strawderman MH, Ernstoff MS, et al.: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group trial EST 1684. Journal of Clinical Oncology 14(1): 7-17, 1996. 81 Kirkwood JM, Ibrahim JG, Sondak VK, et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. Journal of Clinical Oncology 18(12): 2444-2458, 2000. 82 Kirkwood JM, Ibrahim JG, Sondak VK, et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. Journal of Clinical Oncology 18(12): 2444-2458, 2000. 83 Kirkwood JM, Ibrahim JG, Sondak VK, et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. Journal of Clinical Oncology 18(12): 2444-2458, 2000. 80

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(GM2-KLH/QS-21).84 Eight hundred eighty patients were randomized, and 774 were eligible for efficacy analysis. This trial was closed after an interim evaluation indicated the inferiority of the GMK vaccine compared to treatment with interferon. A statistically significant relapsefree survival was found for high-dose interferon (HR=1.47, p=0.0015), as was a statistically significant overall survival benefit (HR=1.52, p=.009). (In the intent-to-treat analysis, relapse-free survival HR=1.49; overall survival HR=1.38.) ·

Clinicians should be aware that the higher dose regimens have significant toxic effects.

·

Autologous bone marrow transplantation with high-dose chemotherapy has not been shown to improve survival.85

Treatment options under clinical evaluation: ·

Because of the higher rate of treatment failure in this group, clinical trials exploring adjuvant chemotherapy and/or adjuvant biologic therapy, or immunologically active agents to prevent recurrences after control of the primary tumors with standard therapy are especially appropriate for newly diagnosed patients.

·

An ongoing phase III trial is evaluating the effect of 1 month of high-dose adjuvant interferon alfa-2b versus observation on relapse-free and overall survival in patients with melanomas greater than 1.5 millimeters in thickness, with or without a single microscopically positive lymph node.86 Another ongoing phase III trial is evaluating adjuvant pegylated interferon alfa-2b versus observation.87 Results are pending from a phase III study that randomized patients with stage II or III disease to adjuvant

Kirkwood JM, Ibrahim JG, Sosmam JA, et al.: High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIb-III melanoma: results of Intergroup trial E1694/S9512/C509801. Journal of Clinical Oncology 19(9): 2370-2380, 2001. 85 Meisenberg BR, Ross M, Vredenburgh JJ, et al.: Randomized trial of high-dose chemotherapy with autologous bone marrow support as adjuvant therapy for high-risk, multi-node-positive malignant melanoma. Journal of the National Cancer Institute 85(13): 1080-1085, 1993. 86 Agarwala S, Eastern Cooperative Oncology Group: Phase III Randomized Adjuvant Study of High Dose Interferon Alfa-2b Therapy in Patients With Stage II and III Melanoma (Summary Last Modified 07/2000), E-1697, clinical trial, active, 12/22/1998. 87 Eggermont AM, EORTC Melanoma Group: Phase III Randomized Study of Adjuvant Pegylated Interferon Alfa in Patients With Previously Resected Stage III Melanoma (Summary Last Modified 09/2000), EORTC-18991, clinical trial, active, 06/20/2000. 84

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intermediate high-dose interferon alfa-2b versus intermediate low-dose interferon alfa-2b versus observation.88 ·

For patients with high-risk stage III disease, phase III clinical trials are evaluating interferon alfa-2b versus chemoimmunotherapy.89

·

For patients with in-transit/satellite lesions (stage IIIC) of the extremities, isolated hyperthermic limb perfusion (ILP) with melphalan (L-PAM) with or without tumor necrosis factor-alfa (TNT-alfa) has resulted in high tumor response rates and palliative benefit.90 Results from a multicenter randomized phase II study showed no benefit from adding interferongamma to a regimen of melphalan plus TNF-alfa.91 Clinical trials are evaluating ILP using melphalan in combination with tumor necrosis factor or other chemotherapeutic agents.92

·

An ongoing phase I/II study is evaluating interferon alfa-2b in combination with radiotherapy.93

Eggermont AM, EORTC Melanoma Group: Phase III Randomized Study of Adjuvant Intermediate High-Dose IFN-A vs Intermediate Low-Dose IFN-A vs Observation Following Definitive Resection of Thick Primary and/or Regional Lymph Node Metastases in HighRisk Stage III Melanoma (Summary Last Modified 08/2000), EORTC-18952, clinical trial, closed, 06/15/2000. 89 Flaherty LE, Southwest Oncology Group: Phase III Randomized Study of Interferon alfa Versus Cisplatin, Vinblastine, and Dacarbazine Plus Interferon alfa and Interleukin-2 in Patients With High-Risk Melanoma (Summary Last Modified 09/2001), SWOG-S0008, clinical trial, active, 08/01/2000. Bedikian AY, University of Texas - MD Anderson Cancer Center: Phase III Randomized Adjuvant Study of Interferon Alfa-2b (IFN-A) Alone vs Biochemotherapy Using Cisplatin, Vinblastine, Dacarbazine (DTIC), IFN-A, and Interleukin-2 (IL-2) in Melanoma Patients with Regional Lymph Node Metastases (Summary Last Modified 08/1998), MDA-ID-95196, clinical trial, active, 11/21/1995. 90 Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. 91 Lienard D, Eggermont AM, Koops HS, et al.: Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study. Melanoma Research 9(5): 491-502, 1999. 92 Fraker DL, American College of Surgeons Oncology Group: Phase III Randomized Study of Hyperthermic Isolated Limb Perfusion and Melphalan With or Without Tumor Necrosis Factor in Patients With Locally Advanced Extremity Melanoma (Summary Last Modified 03/2002), ACOSOG-Z0020, clinical trial, active, 03/03/1999. Brady MS, Memorial Sloan-Kettering Cancer Center: Phase II Study of Isolated Limb Infusion With Melphalan and Dactinomycin in Patients With Primary or Recurrent, Unresectable Regional Melanoma or Soft Tissue Sarcoma of the Extremity (Summary Last Modified 07/2000), MSKCC-99047, clinical trial, active, 08/10/1999. 93 DeConti RC, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida: Phase I/II Study of Adjuvant Radiotherapy Plus Interferon alfa in Patients With Stage III or Recurrent Melanoma (Summary Last Modified 10/2001), MCC-11543, clinical trial, closed, 07/19/2001. 88

266 Melanoma

Stage IV Melanoma Standard treatment options: ·

Melanoma metastatic to distant, lymph node-bearing areas may be palliated by regional lymphadenectomy. Isolated metastases to the lung, GI tract, bone, or occasionally the brain may be palliated by resection with occasional long survival.94 Radiation therapy may provide symptomatic relief for metastases to brain, bones, and viscera.

·

Advanced melanoma is refractory to most standard systemic therapy, and all newly diagnosed patients should be considered candidates for clinical trials. Although advanced melanoma is relatively resistant to therapy, several biologic response modifiers and cytotoxic agents have been reported to produce objective responses.

·

The objective response rate to dacarbazine (DTIC) and the nitrosoureas, carmustine (BCNU) and lomustine (CCNU), is approximately 10% to 20%.95 Responses are usually short-lived, ranging from 3 to 6 months, although long-term remissions can occur in a limited number of patients who attain a complete response.96 Other agents with modest single-agent activity include vinca alkaloids, platinum compounds, and taxanes.97

Leo F, Cagini L, Rocmans P, et al.: Lung metastases from melanoma: when is surgical treatment warranted? British Journal of Cancer 83(5): 569-572, 2000. Ollila DW, Hsueh EC, Stern SL, et al.: Metastasectomy for recurrent stage IV melanoma. Journal of Surgical Oncology 71(4): 209-213, 1999. Gutman H, Hess KR, Kokotsakis JA, et al.: Surgery for abdominal metastases of cutaneous melanoma. World Journal of Surgery 25(6): 750-758, 2001. 95 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. Chapman PB, Einhorn LH, Meyers ML, et al.: Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. Journal of Clinical Oncology 17(9): 2745-2751, 1999. Mays SR, Nelson BR: Current therapy of cutaneous melanoma. Cutis 63(5): 293-298, 1999. 96 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. Mays SR, Nelson BR: Current therapy of cutaneous melanoma. Cutis 63(5): 293-298, 1999. 97 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. 94

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·

Phase II studies of 3-drug combinations showed higher response rates (ranging from 22% to 45%) than were seen with single agents.98 Randomized trials comparing 2- or 3-drug combination regimens with DTIC alone have not consistently demonstrated any advantage for the combination, although these trials had limited sample sizes and insufficient power to detect small but clinically relevant differences in response or survival.99

·

The addition of tamoxifen to the 3-drug combination regimen of cisplatin, BCNU, and DTIC (i.e., the Dartmouth regimen) showed high response rates in phase II studies, with a 20% complete response rate in several trials.100 A phase III trial testing the 3 drugs with and without tamoxifen showed no benefit for the addition of tamoxifen, and the response rates in both study arms were once again in the 20% to 30% range.101

·

One trial directly compared DTIC alone to the 3-drug regimen plus tamoxifen.102 Results from this trial indicated no difference in tumor response or overall survival between the 2 treatment groups. The tumor response rate to DTIC was 10.2%, compared with 18.5% for the 3-drug combination plus tamoxifen (p=.09). Pending the outcome of further randomized, controlled trials, no combination regimen has yet been proven to be superior to DTIC alone.

·

The 2 biologic therapies that appear most active against melanoma are interferon alfa and interleukin-2 (IL-2). Response rates for interferon range from 8% to 22%, and long-term administration on a daily or a 3

Sparano JA, Fisher RI, Sunderland M, et al.: Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. Journal of Clinical Oncology 11(10): 1969-1977, 1993. 98 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. 99 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. 100 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. 101 Rusthoven JJ, Quirt IC, Iscoe NA, et al.: Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. Journal of Clinical Oncology 14(7): 2083-2090, 1996. 102 Chapman PB, Einhorn LH, Meyers ML, et al.: Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. Journal of Clinical Oncology 17(9): 2745-2751, 1999.

268 Melanoma

times per week basis appears superior to once per week or more intermittent schedules.103 Response to IL-2 regimens is similar, in the 10% to 20% range.104 Attempts to improve on this with the addition of lymphokine-activated killer cells (autologous lymphocytes activated by IL-2 ex vivo) and by tumor-infiltrating lymphocytes (lymphocytes derived from tumor isolates cultured in the presence of IL-2) have not improved response rates or durable remissions sufficiently to merit the expense and complexity of this therapy. Phase II studies testing combinations of interferon and IL-2 have demonstrated high response rates, but a phase III comparison of interferon and IL-2 compared with IL-2 alone in 85 patients did not show any benefit for the combination.105 ·

Combinations of chemotherapy and biologics (chemoimmunotherapy or biochemotherapy) have been tested against chemotherapy alone. Four small phase III studies comparing DTIC and interferon with DTIC alone yielded conflicting results.106 In a larger randomized trial involving 271 patients, 258 eligible patients received either DTIC alone; DTIC plus interferon; DTIC plus tamoxifen; or DTIC, interferon, and tamoxifen (2x2 factorial design).107 No statistically significant differences were found in response rates, time-to-treatment failure, or survival among the different groups. Toxic effects were increased in the groups who received interferon.108 [Level of evidence: 1iiA] IL-2 has also been combined with

Agarwala SS, Kirkwood JM: Interferons in melanoma. Current Opinion in Oncology 8(2): 167-174, 1996. 104 Atkins MB, Lotze MT, Dutcher JP, et al.: High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. Journal of Clinical Oncology 17(7): 2105-2116, 1999. Atkins MB, Kunkel L, Sznol M, et al.: High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer Journal from Scientific American 6(suppl 1): S11-S14, 2000. Rosenberg SA, Yang JC, Topalian SL, et al.: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA: Journal of the American Medical Association 271(12): 907-913, 1994. 105 Sparano JA, Fisher RI, Sunderland M, et al.: Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. Journal of Clinical Oncology 11(10): 1969-1977, 1993. 106 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. 107 Falkson CI, Ibrahim J, Kirkwood JM, et al.: Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group Study. Journal of Clinical Oncology 16(5): 1743-1751, 1998. 108 Falkson CI, Ibrahim J, Kirkwood JM, et al.: Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an 103

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cisplatin in several phase II trials109 with encouraging response rates, but data supporting an improvement in survival are lacking. One prospective trial randomized 102 patients to either chemotherapy (DTIC, cisplatin, and tamoxifen) alone or chemotherapy plus IL-2 and interferon alfa-2b.110 No statistically significant differences were found in objective response rate or overall survival between the treatment groups, and toxic side effects were increased in the group that received biochemotherapy. ·

A meta-analysis of 20 randomized trials (involving 3273 patients) that compared single-agent DTIC to combination chemotherapy with or without immunotherapy found that the combination of DTIC and interferon-alfa produced a tumor response rate 53% greater (95% confidence interval, 1.10 to 2.13) than that seen with DTIC alone.111 However, no difference in overall survival was found.

·

Ongoing phase II and III trials are comparing complex biochemotherapy regimens (interferon, IL-2, and chemotherapy) to chemotherapy alone.112

Eastern Cooperative Oncology Group Study. Journal of Clinical Oncology 16(5): 1743-1751, 1998. 109 Demchak PA, Mier JW, Robert NJ, et al.: Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study. Journal of Clinical Oncology 9(10): 1821-1830, 1991. Flaherty LE, Robinson W, Redman BG, et al.: A phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin-2 in metastatic malignant melanoma. Cancer 71(11): 3520-3525, 1993. Atkins MB, O’Boyle KR, Sosman JA, et al.: Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. Journal of Clinical Oncology 12(8): 1553-1560, 1994. 110 Rosenberg SA, Yang JC, Schwartzentruber DJ, et al.: Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa2b. Journal of Clinical Oncology 17(3): 968-975, 1999. 111 Huncharek M, Caubet JF, McGarry R: Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials. Melanoma Research 11(1): 75-81, 2001. 112 Keilholz U, EORTC Melanoma Group: Phase II Randomized Study of Interferon alfa, Dacarbazine, Cisplatin, and Interleukin-2 in Patients With Metastatic Melanoma (Summary Last Modified 08/2000), EORTC-18951, clinical trial, active, 06/01/1995. Gajewski TF, University of Chicago Cancer Research Center: Phase II Study of Cisplatin and Dacarbazine Followed By Sargramostim (GM-CSF), Interferon alfa, and Interleukin-2 in Patients with Metastatic Melanoma (Summary Last Modified 11/1999), UCCRC-9372, clinical trial, active, 08/13/1998. Spitler LE, St. Francis Hospital: Phase II Study of Temozolomide Followed by Sargramostim (GM-CSF), Interleukin-2, and Interferon alfa in Patients With Unresectable Stage IV Melanoma (Summary Last Modified 04/2001), SFMH-BB-IND-5301, clinical trial, active, 12/15/1999. Atkins MB, Eastern Cooperative Oncology Group: Phase III Study of Cisplatin, Vinblastine, and Dacarbazine With or Without Interleukin-2 and Interferon alfa-2b in Patients With

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Pending the results of these and future trials, there is as yet no proof that biochemotherapy is superior to chemotherapy. Treatment options under clinical evaluation: ·

Patients should be considered appropriate candidates for clinical trials evaluating new forms of chemotherapy and/or biologic therapy (specific monoclonal antibodies, interleukin, interferons), or vaccines.

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Palliative radiation therapy for bone, spinal cord, or brain metastases.

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Complete surgical resection of all known disease.113

Recurrent Melanoma Recurrent melanoma is resistant to most standard systemic therapy, and all newly diagnosed patients should be considered candidates for clinical trials. Deciding on further treatment depends on many factors, including prior treatment and site of recurrence, as well as individual patient considerations. Surgery is the most efficacious therapy for isolated recurrence in sites where it can be accomplished (including lymph node, skin, brain, lung, liver, and gastrointestinal sites).114 Although advanced melanoma is relatively resistant to therapy, several biologic response modifiers and cytotoxic agents have been reported to produce objective responses. The objective response rate to dacarbazine (DTIC) and the nitrosoureas, carmustine (BCNU) and lomustine (CCNU), is approximately 10% to 20%.115 Metastatic Malignant Melanoma (Summary Last Modified 06/2002), E-E3695, clinical trial, active, 10/01/1997. 113 Gustin DM, Southwest Oncology Group: Phase II Study of Complete Surgical Resection in Patients With Stage IV Melanoma (Summary Last Modified 12/2001), SWOG-9430, clinical trial, active, 11/15/1996. 114 Wong JH, Skinner KA, Kim KA, et al.: The role of surgery in the treatment of nonregionally recurrent melanoma. Surgery 113(4): 389-394, 1993. Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. Ollila DW, Hsueh EC, Stern SL, et al.: Metastasectomy for recurrent stage IV melanoma. Journal of Surgical Oncology 71(4): 209-213, 1999. 115 Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. Chapman PB, Einhorn LH, Meyers ML, et al.: Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. Journal of Clinical Oncology 17(9): 2745-2751, 1999.

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Responses are usually short-lived, ranging from 3 to 6 months, although long-term remissions can occur in a limited number of patients who attain a complete response.116 Other agents with modest single agent activity include vinca alkaloids, platinum compounds, and taxanes.117 Phase II studies of 3-drug combinations showed higher response rates (ranging from 22% to 45%) than were seen with single agents.118 Randomized trials comparing 2- or 3-drug combination regimens with DTIC alone have not consistently demonstrated any advantage for the combination, although these trials had limited sample sizes and insufficient power to detect small but clinically relevant differences in response or survival.119 The addition of tamoxifen to the 3-drug combination regimen of cisplatin, BCNU, and DTIC (i.e., the Dartmouth regimen) showed high response rates in phase II studies, with a 20% complete response rate in several trials.120 A phase III trial testing the 3 drugs with and without tamoxifen showed no benefit for the addition of tamoxifen, and the response rates for both study arms were once again in the 20% to 30% range.121

Mays SR, Nelson BR: Current therapy of cutaneous melanoma. Cutis 63(5): 293-298, 1999. Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. Mays SR, Nelson BR: Current therapy of cutaneous melanoma. Cutis 63(5): 293-298, 1999. 117 Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. 118 Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. 119 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. 120 Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. 121 Rusthoven JJ, Quirt IC, Iscoe NA, et al.: Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. Journal of Clinical Oncology 14(7): 2083-2090, 1996. 116

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One trial directly compared DTIC alone to the 3-drug regimen plus tamoxifen.122 Results from this trial indicated no difference in tumor response or overall survival between the 2 treatment groups. The tumor response rate to DTIC was 10.2%, compared with 18.5% for the 3-drug combination plus tamoxifen (p=.09). Pending the outcome of further randomized, controlled trials, no combination regimen has yet been proven to be superior to DTIC alone. The 2 biologic therapies that appear most active against melanoma are interferon alfa and interleukin-2 (IL-2). Response rates for interferon range from 8% to 22% and long-term administration on a daily or a 3 times per week basis appears superior to once per week or more intermittent schedules.123 Response to IL-2 regimens is similar, in the 10% to 20% range.124 Attempts to improve on this with the addition of lymphokine-activated killer cells (autologous lymphocytes activated by IL-2 ex vivo) and by tumorinfiltrating lymphocytes (lymphocytes derived from tumor isolates cultured in the presence of IL-2) have not improved response rates or durable remissions sufficiently to merit the expense and complexity of these therapies. Phase II studies testing combinations of interferon and IL-2 have demonstrated high response rates, but a phase III comparison of interferon and IL-2 compared with IL-2 alone in 85 patients did not show any benefit for the combination.125 Combinations of chemotherapy and biologics (chemoimmunotherapy or biochemotherapy) have been tested against chemotherapy alone. Four small phase III studies comparing DTIC and interferon with DTIC alone yielded

Chapman PB, Einhorn LH, Meyers ML, et al.: Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. Journal of Clinical Oncology 17(9): 2745-2751, 1999. 123 Agarwala SS, Kirkwood JM: Interferons in melanoma. Current Opinion in Oncology 8(2): 167-174, 1996. 124 Atkins MB, Lotze MT, Dutcher JP, et al.: High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. Journal of Clinical Oncology 17(7): 2105-2116, 1999. Atkins MB, Kunkel L, Sznol M, et al.: High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer Journal from Scientific American 6(suppl 1): S11-S14, 2000. Rosenberg SA, Yang JC, Topalian SL, et al.: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA: Journal of the American Medical Association 271(12): 907-913, 1994. 125 Sparano JA, Fisher RI, Sunderland M, et al.: Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. Journal of Clinical Oncology 11(10): 1969-1977, 1993. 122

Physician Guidelines and Databases 273

conflicting results.126 In a larger randomized trial involving 271 patients, 258 eligible patients received either DTIC alone; DTIC plus interferon; DTIC plus tamoxifen; or DTIC, interferon, and tamoxifen (2X2 factorial design).127 No statistically significant differences were found in response rates, time-totreatment failure, or survival among the different groups. Toxic side effects were increased in the groups who received interferon.128 [Level of evidence: 1iiA] IL-2 has also been combined with cisplatin in several phase II trials129 with encouraging response rates, but data supporting an improvement in survival are lacking. One prospective trial randomized 102 patients to either chemotherapy (DTIC, cisplatin, and tamoxifen) alone or chemotherapy plus IL-2 and interferon alfa-2b.130 No statistically significant differences were found in objective response rate or overall survival between the treatment groups, and toxic side effects were increased in the group that received biochemotherapy. A meta-analysis of 20 randomized trials (involving 3273 patients) that compared single-agent DTIC to combination chemotherapy with or without immunotherapy found that the combination of DTIC and interferon-alfa produced a tumor response rate 53% greater (95% confidence interval, 1.10

Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology (Huntington NY) 9(11): 1149-1158, (discussion 1163-1164, 1167-1168), 1995. 127 Falkson G, Gelman RS, Pandya KJ, et al.: Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment. Journal of Clinical Oncology 16(5): 1669-1676, 1998. 128 Falkson G, Gelman RS, Pandya KJ, et al.: Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment. Journal of Clinical Oncology 16(5): 1669-1676, 1998. 129 Demchak PA, Mier JW, Robert NJ, et al.: Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study. Journal of Clinical Oncology 9(10): 1821-1830, 1991. Flaherty LE, Robinson W, Redman BG, et al.: A phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin-2 in metastatic malignant melanoma. Cancer 71(11): 3520-3525, 1993. Atkins MB, O’Boyle KR, Sosman JA, et al.: Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. Journal of Clinical Oncology 12(8): 1553-1560, 1994. 130 Rosenberg SA, Yang JC, Schwartzentruber DJ, et al.: Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa2b. Journal of Clinical Oncology 17(3): 968-975, 1999. 126

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to 2.13) than that seen with DTIC alone.131 However, no difference in overall survival was found. Two ongoing phase III trials are comparing complex biochemotherapy regimens (interferon, IL-2, and chemotherapy) to chemotherapy alone.132 Pending the results of these and future trials, there is no proof that biochemotherapy is superior to chemotherapy. Isolated hyperthermic limb perfusion (ILP) with melphalan (L-PAM) with or without tumor necrosis factor-alfa (TNT-alfa) has been associated with high tumor response rates and substantial palliative benefit.133 For patients with extremity recurrences, ILP with melphalan was shown in a randomized trial to increase disease-free survival, but had no effect on overall survival.134 Prolonged disease-free intervals have been reported in patients undergoing repeat ILPs for recurrence after initial complete responses.135 Ongoing clinical trials are evaluating ILP using melphalan in combination with tumor necrosis factor or other chemotherapeutic agents.136 Although melanoma is a relatively radiation-resistant tumor, palliative radiation therapy may alleviate symptoms. Retrospective studies have shown that patients with multiple brain metastases, bone metastases, and Huncharek M, Caubet JF, McGarry R: Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials. Melanoma Research 11(1): 75-81, 2001. 132 Atkins MB, Eastern Cooperative Oncology Group: Phase III Study of Cisplatin, Vinblastine, and Dacarbazine With or Without Interleukin-2 and Interferon alfa-2b in Patients With Metastatic Malignant Melanoma (Summary Last Modified 06/2002), E-E3695, clinical trial, active, 10/01/1997. Flaherty LE, Southwest Oncology Group: Phase III Randomized Study of Interferon alfa Versus Cisplatin, Vinblastine, and Dacarbazine Plus Interferon alfa and Interleukin-2 in Patients With High-Risk Melanoma (Summary Last Modified 09/2001), SWOG-S0008, clinical trial, active, 08/01/2000. 133 Wagner JD, Gordon MS, Chuang TY, et al.: Current therapy of cutaneous melanoma. Plastic and Reconstructive Surgery 105(5): 1774-1799, 2000. 134 Hafstrom L, Rudenstam CM, Blomquist E, et al.: Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. Journal of Clinical Oncology 9(12): 2091-2094, 1991. 135 Feldman AL, Alexander HR Jr, Bartlett DL, et al.: Management of extremity recurrences after complete responses to isolated limb perfusion in patients with melanoma. Annals of Surgical Oncology 6(6): 562-567, 1999. 136 Fraker DL, American College of Surgeons Oncology Group: Phase III Randomized Study of Hyperthermic Isolated Limb Perfusion and Melphalan With or Without Tumor Necrosis Factor in Patients With Locally Advanced Extremity Melanoma (Summary Last Modified 03/2002), ACOSOG-Z0020, clinical trial, active, 03/03/1999. Brady MS, Memorial Sloan-Kettering Cancer Center: Phase II Study of Isolated Limb Infusion With Melphalan and Dactinomycin in Patients With Primary or Recurrent, Unresectable Regional Melanoma or Soft Tissue Sarcoma of the Extremity (Summary Last Modified 07/2000), MSKCC-99047, clinical trial, active, 08/10/1999. 131

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spinal cord compression may achieve symptom relief and some shrinkage of the tumor with radiation therapy.137 The most effective dose-fractionation schedule for palliation of melanoma metastatic to the bone or spinal cord is unclear, but high-dose-per-fraction schedules are sometimes used to overcome tumor resistance. An ongoing phase I/II clinical trial is evaluating adjuvant radiotherapy plus interferon in patients with recurrent melanoma.138 Standard treatment options: ·

Resection of isolated single or localized metastases from skin, visceral, or brain sites in selected patients is sometimes associated with prolonged survival.

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Palliative radiation therapy for bone, spinal cord, or brain metastases.

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Palliative biologic therapy and/or chemotherapy in phase I and II clinical trials.

·

Palliative treatment with interleukin-2 or interferon can occasionally result in prolonged survival.

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Isolated hyperthermic limb perfusion for extremity recurrences.

Rate WR, Solin LJ, Turrisi AT: Palliative radiotherapy for metastatic malignant melanoma: brain metastases, bone metastases, and spinal cord compression. International Journal of Radiation Oncology, Biology, Physics 15(4): 859-864, 1988. Herbert SH, Solin LJ, Rate WR, et al.: The effect of palliative radiation therapy on epidural compression due to metastatic malignant melanoma. Cancer 67(10): 2472-2476, 1991. 138 DeConti RC, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida: Phase I/II Study of Adjuvant Radiotherapy Plus Interferon alfa in Patients With Stage III or Recurrent Melanoma (Summary Last Modified 10/2001), MCC-11543, clinical trial, closed, 07/19/2001. 137

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.139 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:140 ·

Bioethics: Access to published literature on the ethical, legal and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to caner-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 140 See http://www.nlm.nih.gov/databases/databases.html. 139

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·

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

While all of the above references may be of interest to physicians who study and treat melanoma, the following are particularly noteworthy.

The Combined Health Information Database A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to “Brochure/Pamphlet,” “Fact Sheet,” or “Information Package” and melanoma using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years,” select your preferred language, and the format option “Fact Sheet.” By making these selections and typing “melanoma” (or synonyms) into the “For these words:” box above, you will only receive results on fact sheets dealing with melanoma. The following is a sample result:

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·

Cancer in Minnesota: Racial and Ethnic Disparities: A Report on Cancers for Which Prevention or Early Detection Can Make a Difference Source: Minneapolis, MN, Minnesota Department of Health, Division of Chronic Disease Prevention and Control, 4 p., October 2001. Contact: Minnesota Department of Health, Division of Chronic Disease Prevention and Control, P.O. Box 9441, Minneapolis, MN 55440. (612) 676-5500. FAX: (612) 676-5520. Internet/Email: www.health.state.mn.us; http://www.health.state.mn.us/divs/dpc/cc/info/disparit.pdf. Summary: This report provides information on cancer incidence and mortality rates in Minnesota by race and ethnicity for cancers for which prevention and/or early detection has been shown to save lives. This includes cancers of the breast, cervix, colon and rectum, lung, prostate, and skin. Data is available by race for American Indians, Asian/Pacific Islanders, blacks, and whites. The breast cancer mortality rate in Minnesota is 50 percent higher in black women than in white nonHispanic women even though the incidence rates are similar. Black women in Minnesota have a cervical cancer incidence rate four times as high as the rate for white women. Lung cancer mortality rates for American Indian men, American Indian women, and black men are nearly double the rates for whites. The prostate cancer incidence rate is one-third higher in black men than whites. Colorectal cancer mortality is higher among white non-Hispanic women than Hispanic white women. White men have an incidence rate of melanoma nine times as high as the rate for nonwhite men. The report suggests areas for which targeted cancer control activities may be warranted.

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2001 Cancer Progress Report Source: Bethesda, MD, NCI Public Inquiries Office, 76 p., December 2001. Contact: NCI Public Inquiries Office, Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 422-6237. Internet/Email: http://progressreport.cancer.gov; http://progressreport.cancer.gov/additionalMaterials/sectionPDFs/NC I_CPR200 1.PDF. Publication no. 02-5045. Summary: 2001 Cancer Progress Report is the official report from the National Cancer Institute (NCI) of the nation's progress against cancer. The goal of this report is to establish a readily accessible, authoritative tool to track such progress over time. This report is not just a report of progress within the NCI. It also reflects efforts by other federal agencies, foundations, and state and local governments and health departments, as well as medical providers and researchers, cancer patients and advocates,

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and others concerned with making cancer an easily treated disease. This report includes key measures of progress in the areas of (1) prevention, (2) early detection, (3) diagnosis, (4) treatment, (5) life after cancer, and (6) end of life. Selected results showed that (1) rates of new cancer cases and cancer deaths are falling overall; (2) some prevention behaviors have shown improvement; (3) the use of screening tests for breast, cervical, and colorectal cancers is increasing; (4) some cancers, such as esophageal cancer and melanoma, are rising dramatically; (5) youth smoking is increasing; (6) people are doing less to protect themselves from the sun; (7) more people are overweight and obese, and physical activity is increasing only slightly; and (8) unexplained cancer-related health disparities remain among population subgroups. The report concludes that the nation is making progress against cancer, but much work remains to reach Healthy People 2010 targets. ·

Research Utilizing the California Cancer Registry Source: Cancer Surveillance Section, California Department of Health Services, 140 p., June 2000. Contact: Cancer Surveillance Section, Cancer Control Branch, Division of Chronic Disease and Injury Control, California Department of Health Services, 1700 Tribute Road, Suite 100, Sacramento, CA 95815-4402. (916) 779-0300. Internet/Email: http://www.dhs.cahwnet.gov/ps/cdic/cdicindex.htm. Summary: The California Cancer Registry (CCR) serves as the foundation for multidisciplinary cancer research in California. Since 1988, over 270 cancer research projects have been conducted using CCR data, bringing in approximately $203,916,199 in research funds to California. This report summarizes CCR-based research from 1988 to the present. CCR research project abstracts contained in this report deal with the following cancers: (1) Breast, (2) brain, (3) cervical, (4) colorectal, (5) corpus uteri, (6) Kaposi's sarcoma, (7) kidney and renal, (8) leukemia, (9) liver, (10) lung, (11) lymphoma, (12) melanoma, (13) myeloma, (14) oral cavity and pharynx, (15) ovarian, (16) pancreatic, (17) prostate gland, (18) testicular, (19) skin, (20) stomach, (21) thyroid, (22) urinary and bladder, and (23) multiple cancers. Information is also provided concerning CCR linkage studies and CCR response to cancer concerns. Appendix A offers a description of datasets. Appendix B contains a directory of regional registries. Appendix C contains a regional cancer registries map.

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Cancer in California, 2001 Source: Sacramento, CA, California Department of Health Services, Cancer Surveillance Section, 15 p., 2000.

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Contact: California Department of Health Services, Cancer Surveillance Section, 1700 Tribute Road, Suite 100, Sacramento, CA 95815-4402. (916) 779-0300. Internet/Email: http://www.ccrcal.org; http://www.dhs.cahwnet.gov/ps/cdic/cdicindex/htm. Summary: Cancer in California, 2001 summarizes cancer statistics in California as a result of 11 years of statewide cancer registration. The authors provide data on (1) expected new cancer cases and deaths, (2) prevalence and lifetime risk of diagnosis with cancer, (3) cancer trends, (4) trends in smoking-related cancers, (5) trends in cancer incidence by stage at diagnosis, (6) racial and ethnic differences in cancer risk, (7) racial and ethnic mortality trends, (8) childhood cancer, and (9) California statistics compared to the rest of the nation. About 135,000 Californians will be diagnosed with cancer in 2001. Cancer is second only to heart disease in cause of death. Breast and prostate cancer are the most commonly diagnosed cancers, but lung cancer accounts for more deaths than breast, prostate, colon, and rectum cancers combined. Based on current rates, more than two out of five Californians will be diagnosed with cancer during their lifetime. The incidence and mortality rates of all cancers combined have decreased since 1990. However, liver cancer has increased by more than 40 percent since 1988. Melanoma has also increased since 1988, although melanoma incidence and mortality has decreased since 1997. Smoking-related cancers have decreased since 1988. Black males have the highest overall cancer rates. Among females, whites have the highest cancer rates, but blacks have the highest mortality rates. Racial/ethnic differences are likely to be causes by dietary, lifestyle, socioeconomic, environmental, and genetic factors. Cancer is the leading cause of childhood death. ·

Run the Good Race: Cancer Prevention and Control in Missouri Source: Jefferson City, MO, Missouri Department of Health, 35 p., 2000. Contact: Missouri Department of Health, Bureau of Cancer Control, P.O. Box 570, Jefferson City, MO 65102-0570. (800) 316-0935. Summary: Run the Good Race: Cancer Prevention and Control in Missouri provides up-to-date information on the status of cancer in Missouri and efforts being taken to diminish its effects. Cancer is the second leading cause of death for Missourians. The report discusses the incidence, mortality, risk factors, effects of poverty, overall rates of cancer incidence, and specific cancers of concern in Missouri, such as lung, colorectal, breast, prostate, cervical, and melanoma. The cost of cancer is considered in terms of years of potential life lost, economic cost of cancer, and costs that cannot be measured in dollars. Also included is information on screening guidelines. Cancer control coalitions are listed

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along with allied agencies. Frequently asked questions are answered and sources are provided for further research. ·

Action Plan on Skin Cancer for the State of Texas Source: Austin, TX, Texas Cancer Council, 52 p., August 2000. Contact: Texas Cancer Council, P.O. Box 12097, Austin, TX 78711. (512) 463-3190. Summary: Action Plan on Skin Cancer for the State of Texas identifies current skin cancer education, prevention, detection, and treatment resources, recommending approaches and resources that must be developed to thoroughly evaluate and reduce the incidence of skin cancer in the state. It takes into account the demographic diversity of its people and the urgency of making skin cancer awareness and prevention a part of daily life. The report discusses (1) incidence, mortality, and impact on society; (2) basal cell carcinoma, squamous cell carcinoma, and malignant melanoma; (3) contributing and causative factors, including ultraviolet radiation; (4) prevention; (5) cancer prevention and information services that impact the skin cancer problem; (6) barriers to early detection and treatment of skin cancer in Texas; (7) policy initiatives that would affect skin cancer awareness and prevention; (8) professional practice regarding skin cancer prevention, detection, and treatment; and (9) prevention and information models. The Action Plan includes four goals: (1) Initiate data collection and analysis; (2) develop prevention information and services to increase public awareness; (3) enhance professional education and practice; and (4) improve access to prevention, detection, and treatment. Appendices provide data on skin cancer morbidity and mortality, counties reporting health care availability as an issue, federally designated medically underserved areas, and additional Texas Cancer Council initiatives.

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Basal Cell Carcinoma Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2001. 8 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail: [email protected]. Website: www.aad.org. Price: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have basal cell carcinoma with information on the etiology, features, diagnosis, treatment, and prevention of this common skin cancer. Basal cell cancer does not metastasize or travel in the bloodstream

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to other organs. Most cases are believed to be caused by exposure to the harmful ultraviolet rays of the sun, and basal cell cancer most often appears on sun exposed areas. Basal cell tumors have several different forms, with the most common being a small dome shaped bump that has a pearly white color. Other presentations include a pimple like growth that heals but recurs or a smooth white or yellowish waxy scar. A very common sign of basal cell cancer is a sore that bleeds and heals up but recurs. Diagnosis is based on the results of a biopsy of the growth. Surgical options for removing the growth include electrodesiccation and curettage and simple surgical excision. Other treatments, such as cryosurgery, radiation therapy, and laser surgery, may be used in certain situations. Cosmetic outcomes following surgery are usually excellent. Untreated basal cell cancer will continue to grow locally and may cause serious problems if it is located near the eyes, ears, nose, or other important organs. People who have had one basal cell cancer are at a 40 percent risk of getting a second basal cell cancer within 5 years, and people who have had multiple basal cell cancers or other skin cancers are at an increased risk for melanoma. Proper sun protection may help prevent the development of further basal cell cancers. 4 figures. ·

Atypical Nevus Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2001. 6 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail: [email protected]. Website: www.aad.org. Price: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have an atypical nevus with information on this benign growth that may share some of the clinical or microscopic features of melanoma. Although an atypical nevus is not a melanoma, the presence of atypical nevi may increase the risk of developing a melanoma. Atypical nevi can have a variable appearance. Features include being asymmetrical, variably colored, large, and slightly raised and having an irregular border. Atypical nevi can occur anywhere on the body, but they are more common in sun exposed areas. A person who has multiple atypical and normal nevi and a relative who has melanoma may have Familial Atypical Mole Syndrome (FAMS). Anyone diagnosed with FAMS is at significantly increased risk of developing melanoma, so he or she should perform a skin self examination every 2 to 3 months. Patients should also undergo a full body screen from their dermatologist every 3 to 12 months. Avoidance of ultraviolet light is important to help prevent

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the development of melanoma. Other preventive measures include using sunscreen and wearing protective clothing. 2 figures. ·

What You Need to Know About Moles and Dysplastic Nevi Source: Bethesda, MD: National Cancer Institute (NCI). 1999. 26 p. Contact: Available from National Cancer Institute, Cancer Information Service, Publications Ordering Service. P.O. Box 24128, Baltimore, MD 21227. (800) 4-CANCER. Price: Up to 20 items free; shipping charges apply on larger orders. Summary: This booklet provides the general public with information on common and atypical moles. The booklet describes what common and atypical moles look like and explains how moles may be related to a form a skin cancer known as melanoma. Other topics include the signs of melanoma, the risk factors for melanoma, the technique used to self check the skin for moles that might be cancerous, and the importance of protecting the skin. In addition, the booklet includes pictures of ordinary and atypical moles and melanomas, a glossary, and a list of National Cancer Institute information resources.

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Sun Fitness for All Ages Source: New York, NY: Skin Cancer Foundation. 1999. 12 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail: [email protected]. Website: www.skincancer.org. Price: Contact for current pricing; bulk orders available. Item No. BR-17. Summary: This illustrated booklet provides the general public with information on sun protection. Although the sun gives people a sense of warmth and well being, almost all of the effects of exposure to ultraviolet A and B rays are damaging to the skin. Too much sun exposure may cause basal cell carcinoma; squamous cell carcinoma; or melanoma, the most dangerous form of skin cancer. People who are at greatest risk of skin damage and skin cancers have fair skin that burns but does not tan; freckles; blond, red, or light brown hair; and blue, green, or gray eyes. People who have a large number of common moles or any atypical moles are at increased risk of developing melanoma. The warning signs of skin cancer include a skin growth that increases in size and is pearly, translucent, tan, brown, black, or multicolored; a mole that changes its color or texture, has an irregular border, increases in size or thickness, or is larger than a pencil eraser; a spot or growth that itches, hurts, crusts, scabs, erodes, or bleeds; an open sore that does not heal; and a new mole that appears after age 21. The booklet discusses special sun protection

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concerns for babies, children, adolescents, adults, and older adults and provides a sun fitness checklist for all ages. ·

Dermatologic Surgery Source: Schaumburg, IL: American Academy of Dermatology. 1998. 8 p. Contact: American Academy of Dermatology. Communications Department, 930 North Meacham Road, P.O. Box 4014, Schaumburg, IL 60168-4014. (847) 330-0230. Fax (847) 330-0050. Website: www.aad.org. Price: Contact for pricing information; bulk discounts available. Summary: This pamphlet for the general public focuses on dermatologic surgery. It presents reasons for performing skin surgery, including preventing or providing early control of disease, improving the appearance of the skin, and establishing a definite diagnosis. Types of skin cancer are identified, including basal cell cancer, squamous cell cancer, and malignant melanoma. Common forms of treatment for skin cancer are explained, including curettage and electrodesiccation, surgical excision, cryosurgery, Mohs' surgery, topical chemotherapy, and radiation therapy. Other skin blemishes that may be eliminated or improved by a dermatological surgical procedure are described, including age or liver spots, birthmarks, moles, warts, scars, wrinkles, actinic or seborrheic keratoses, cysts, and baldness. In addition, the pamphlet presents the events of a typical visit to the dermatologist's office.

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Seborrheic Keratoses Source: Schaumburg, IL: American Academy of Dermatology. 1997. 6 p. Contact: American Academy of Dermatology, 930 North Meacham Road, P.O. Box 4014, Schaumburg, IL 60168-4014. Summary: This pamphlet for the general public uses a question-andanswer format to discuss seborrheic keratoses, which are noncancerous growths of the outer layer of skin. The pamphlet explains the cause of these growths and how serious they are, identifies the most common places for them to appear. The individuals who may be susceptible to them, and discusses the treatment and prevention of these growths. In addition, the pamphlet presents the differences between seborrheic keratoses and warts, moles, actinic keratoses, and melanoma. 3 photographs.

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Aging Skin Source: Schaumburg, IL: American Academy of Dermatology. 1997. 10 p.

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Contact: Available from American Academy of Dermatology. P.O. Box 681069, Schaumburg, IL 60168-1069. (888) 462-3376 or (847) 330-0230. http://www.aad.org/index.html. Price: Single copy free; bulk prices available. Summary: This brochure for the general public describes skin changes that occur as a result of the aging process. It explains why wrinkles occur and how those caused by sun exposure can be prevented. The brochure identifies treatments for aging and dry skin. It describes skin growths and lesions that become common as individuals age, including actinic keratoses, age or liver spots, seborrheic keratoses, cherry angiomas, and broken capillaries or telangiectasia. Other skin lesions include basal and squamous cell carcinoma and malignant melanoma. In addition, the brochure highlights skin diseases that are more common in older people, including shingles, seborrheic dermatitis, varicose veins, varicose ulcers, bruising, and itching. 6 photographs and 1 table. ·

Ultraviolet Index: What You Need to Know Source: Schaumburg, IL: American Academy of Dermatology. 1996. 8 p. Contact: Available from American Academy of Dermatology. P.O. Box 681069, Schaumburg, IL 60168-1069. (888) 462-3376 or (847) 330-0230. http://www.aad.org/index.html. Price: Single copy free; bulk prices available. Summary: This brochure for the general public provides information on the ultraviolet light (UV) index. It explains that the UV index gives the next day's amount of exposure to UV rays and predicts UV levels on a 0 to 10+ scale. The brochure also discusses the various factors that affect sun exposure, as well as the ozone layer which protects the Earth from harmful UV rays. Decreases in the ozone layer have led to increases in the amount of UV radiation reaching the Earth's surface. The brochure also describes the effects of exposure to the sun including sunburn, tanning, premature wrinkling, basal and squamous cell cancer, melanoma, eye damage, allergic reactions, and immune system suppression. It outlines the many precautions to take for preventing skin cancer and eye damage, and states that children should be kept indoors during peak sunlight hours; sunscreen should be applied to those older than six months. 1 table.

·

Sun Protection for Children Source: Schaumburg, IL: American Academy of Dermatology. 1996. 8 p. Contact: Available from American Academy of Dermatology. P.O. Box 681069, Schaumburg, IL 60168-1069. (888) 462-3376 or (847) 330-0230.

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http://www.aad.org/index.html. Price: Single copy free; bulk prices available. Summary: This brochure for the general public uses a question and answer format to provide parents with information about protecting their children from the damaging effects of the sun. It explains that invisible ultraviolet light rays enter the skin and cause visible and invisible damage, including sunburn and cell damage that eventually appears as wrinkles, age spots, or skin cancer. Severe sunburns may be related to the development of melanoma. The brochure stresses that sun protection should begin in infancy and continue for a lifetime and that parents should teach their children to follow the ABCs of sun protection. 'A' stands for staying out of the sun during the middle of the day when the sun's energy is greatest. It also means avoiding long periods of sun exposure and avoiding sunburn. 'B' stands for blocking sun damage by using a broad-spectrum sunscreening agent. 'C' stands for covering up with a hat and dark clothing when outdoors. 'S' is for speaking out about to family and friends about sun protection. 1 figure. ·

Black Skin Source: Schaumburg, IL: American Academy of Dermatology. 1994. 8 p. Contact: Available from American Academy of Dermatology. P.O. Box 681069, Schaumburg, IL 60168-1069. (888) 462-3376 or (847) 330-0230. http://www.aad.org/index.html. Price: Single copy free; bulk prices available. Summary: This brochure for African Americans provides information on skin, hair, and nail conditions that more commonly affect this ethnic group. It explains that African Americans may experience dry skin, variations in skin color, vitiligo, pityriasis alba, dermatosis papulosa nigra, keloids, and folliculitis keloidalis. Problems with hair loss or breaking may occur as a result of certain techniques and preparations used to treat African American hair. Other hair-related conditions include tinea capitis and ingrown hairs of the beard. The brochure highlights the features of and treatments for these conditions. It also notes that African Americans should be aware that increased darkening around the base of the nail could be a sign of malignant melanoma. 7 photographs.

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Sun, Your Skin, and Your Health Source: New York, NY: American Skin Association. 199x. 7 p.

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Contact: Available from American Skin Association. 150 East 58th Street, 32nd Floor, New York, NY 10155-0002. (800) 499-SKIN or (212) 753-8260. Fax (212) 688-6547. Price: Single copy free; bulk orders available at cost. Summary: This pamphlet provides the general public with information about the dangers of exposing unprotected skin to the sun. Two major adverse effects are skin cancer and premature aging. Skin cancer is the most common type of cancer, and up to 90 percent of the signs of skin aging are caused by unprotected exposure to the sun. The pamphlet highlights the warning signs of basal and squamous cell carcinoma and melanoma, outlines ways to prevent skin damage or disease, and presents ways to protect others from exposure to the sun. In addition, the pamphlet stresses the need to end the practice of suntanning. An insert presents various skin types and their reaction to sun exposure and provides examples of each.

The NLM Gateway141 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing “one-stop searching” for many of NLM’s information resources or databases.142 One target audience for the Gateway is the Internet user who is new to NLM’s online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, researchers, librarians, students, and, increasingly, patients, their families, and the public.143 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “melanoma” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 143 Other users may find the Gateway useful for an overall search of NLM’s information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 141 142

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Results Summary Category Items Found Journal Articles 352276 Books / Periodicals / Audio Visual 2590 Consumer Health 294 Meeting Abstracts 2575 Other Collections 87 Total 357822

HSTAT144 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.145 HSTAT’s audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-reference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.146 Simply search by “melanoma” (or synonyms) at the following Web site: http://text.nlm.nih.gov. Coffee Break: Tutorials for Biologists147 Some patients may wish to have access to a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. To this end, we Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. The HSTAT URL is http://hstat.nlm.nih.gov/. 146 Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration’s Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force’s Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 147 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 144 145

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recommend “Coffee Break,” a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.148 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.149 This site has new articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are a few examples that may interest you: ·

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

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Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center’s MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.

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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

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MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.

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Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 149 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 148

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vocabularies; see the following http://www.lexical.com/Metaphrase.html.

Web

site:

The Genome Project and Melanoma With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and patients want to know about how human genes relate to melanoma. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).150 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “melanoma” (or synonyms) in the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. By following these links, especially the link titled “Database Links,” you will be exposed to numerous specialized databases that are largely used by the scientific community. These databases are overly technical and seldom used by the general public, but offer an abundance of information. The following is an example of the results you can obtain from the OMIM for melanoma: ·

Absent in Melanoma 1 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?601797

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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·

Absent in Melanoma 2 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?604578

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B Melanoma Antigen Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?605167

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Melanoma Adhesion Molecule Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?155735

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Melanoma Antigen Recognized by T Cells 2 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?605743

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Melanoma Antigen, Family A, 1 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?300016

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Melanoma Antigen, Family A, 10 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?300343

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Melanoma Antigen, Family A, 11 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?300344

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Melanoma Antigen, Family A, 12 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?300177

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Melanoma Antigen, Family A, 2 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?300173

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Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by the system of the body associated with it. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to re-visit it from time to time. The following systems and associated disorders are addressed: ·

Cancer: Uncontrolled cell division. Examples: Breast And Ovarian Cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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·

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” In the box next to “for,” enter “melanoma” (or synonyms) and click “Go.”

Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database151 This online resource can be quite useful. It has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At the following Web site you can also search across syndromes using an index: http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html. You can search by keywords at this Web site: http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

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The Genome Database152 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “melanoma” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms). This database is extremely technical as it was created for specialists. The articles are the results which are the most accessible to non-professionals and often listed under the heading “Citations.” The contact names are also accessible to non-professionals.

Specialized References The following books are specialized references written for professionals interested in melanoma (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): · Advanced and Critical Care Oncology Nursing: Managing Primary Complications by Cynthia C. Chernecky (Editor), et al; Paperback - 736 pages (September 18, 1997), W B Saunders Co; ISBN: 0721668607; http://www.amazon.com/exec/obidos/ASIN/0721668607/icongroupinterna · Cancer: Etiology, Diagnosis, and Treatment by Walter J. Burdette; Paperback - 287 pages, 1st edition (January 15, 1998), McGraw Hill Text; Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html#mission.

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ISBN: 0070089922; http://www.amazon.com/exec/obidos/ASIN/0070089922/icongroupinterna · Cancer Management: A Multidisciplinary Approach: Medical, Surgical & Radiation by Richard Pazdur (Editor), et al; Paperback - 982 pages, 5th edition (June 15, 2001), Publisher Research & Representation, Inc.; ISBN: 1891483080; http://www.amazon.com/exec/obidos/ASIN/1891483080/icongroupinterna · Familial Cancer and Prevention: Molecular Epidemiology: A New Strategy Toward Cancer Control by Joji Utsunomiya (Editor), et al; Hardcover (April 1999), Wiley-Liss; ISBN: 0471249378; http://www.amazon.com/exec/obidos/ASIN/0471249378/icongroupinterna · Fundamentals of Cancer Epidemiology by Philip C. Nasca, Ph.D. (Editor), Pastides Harris, Ph.D., MPH (Editor); Hardcover - 368 pages, 1st edition (February 15, 2001), Aspen Publishers, Inc.; ISBN: 0834217767; http://www.amazon.com/exec/obidos/ASIN/0834217767/icongroupinterna · Helping Cancer Patients Cope: A Problem-Solving Approach by Arthur M. Nezu (Editor), et al; Hardcover - 314 pages (December 15, 1998), American Psychological Association (APA); ISBN: 1557985332; http://www.amazon.com/exec/obidos/ASIN/1557985332/icongroupinterna · Quantitative Estimation and Prediction of Human Cancer Risks (Iarc Scientific Publications, 131) by Suresh H. Moolgavkar (Editor), et al; Paperback (September 1999), Oxford University Press; ISBN: 9283221311; http://www.amazon.com/exec/obidos/ASIN/9283221311/icongroupinterna · Textbook of Cancer Epidemiology by ADAMI, et al; Hardcover - 385 pages, 1st edition (July 15, 2002), Oxford University Press; ISBN: 0195109694; http://www.amazon.com/exec/obidos/ASIN/0195109694/icongroupinterna

Vocabulary Builder Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Corpus: The body of the uterus. [NIH] Dermatosis:

Any skin disease, especially one not characterized by

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inflammation. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH]

Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Folliculitis: Inflammation of a follicle or follicles; used ordinarily in reference to hair follicles, but sometimes in relation to follicles of other kinds. [EU]

Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Hematogenous: bloodstream. [NIH]

Originating in the blood or spread through the

Histology: The study of tissues and cells under a microscope. [NIH] Hyperplasia: An abnormal increase in the number of cells in an organ or tissue. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Keloid: A thick, irregular scar caused by excessive tissue growth at the site of an incision or wound. [NIH] Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. Also called lymph node dissection. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Nitrosoureas: A group of anticancer drugs that can cross the blood-brain barrier. Carmustine and lomustine are nitrosoureas. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Pityriasis: A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. [EU] Platinum: A metal that is an important component of some anticancer drugs, such as cisplatin and carboplatin. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which

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refers to the number of new cases in the population at a given time. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Taxanes: Anticancer drugs that inhibit cancer cell growth by stopping cell division. Also called antimitotic or antimicrotubule agents or mitotic inhibitors. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Testicular: Pertaining to a testis. [EU] Ulceration: 1. the formation or development of an ulcer. 2. an ulcer. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Veins: The vessels carrying blood toward the heart. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH]

Dissertations 299

CHAPTER 10. DISSERTATIONS ON MELANOMA Overview University researchers are active in studying almost all known diseases. The result of research is often published in the form of Doctoral or Master’s dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to melanoma. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.

Dissertations on Melanoma ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to melanoma. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with melanoma: ·

Analysis of Dna Sequences in a Human Melanoma by Higgins, Michael Joseph; PhD from Queen's University at Kingston (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL38467

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·

Association between Dna Amplification and Enhanced Malignancy in a Human Melanoma Cell-line by Gitelman, Inna; PhD from Queen's University at Kingston (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL32189

·

Cell Kinetics of B16 Melanoma and the Induction of in Vivo Cell Synchrony by Cytosine Arabinoside by Gibson, Maurice Henry Lindsay; PhD from The University of Manitoba (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK10964

·

Characterization and Partial Purification of the 22-kilodalton Psoralen Binding Protein from S91 Mouse Melanoma Cells by Dowdy, John Carlton; PhD from The University of Memphis, 2001, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3003738

·

Cutaneous Malignant Melanoma: a Study of Skin Cancer in the United States from 1973--1997 by Mcoliver, Cynthia Chioma; MPh from The Univ. of Texas H.s.c. at Houston Sch. of Public Health, 2001, 66 pages http://wwwlib.umi.com/dissertations/fullcit/1406492

·

Does Use of Tetracyclines among Veterans Increase Their Risk for Melanoma? by Fagan, Nancy Kitchin; PhD from University of South Florida, 2001, 117 pages http://wwwlib.umi.com/dissertations/fullcit/3030306

·

Effective Immunotherapy of Murine Melanoma by in Vivo Electroporation by Lucas, Melinda Lee (bradford); PhD from University of South Florida, 2001, 110 pages http://wwwlib.umi.com/dissertations/fullcit/3041114

·

FAS Ligand and Soluble Fas-opposing Molecules in Melanoma Lung Metastasis by Hall, Christopher Louis; PhD from The Univ. of Texas H.s.c. at Houston Grad. Sch. of Biomed. Sci., 2001, 114 pages http://wwwlib.umi.com/dissertations/fullcit/3013879

·

Malignant Melanoma in Southern Sweden: Histopathology, Prognosis and Aetiology by Masback, Anna; from Lunds Universitet (Sweden), 2002, 118 pages http://wwwlib.umi.com/dissertations/fullcit/f125009

·

Melanoma Models for Chemoprevention and Ultraviolet Radiation Susceptibility by Lluria-prevatt, Maria Del Carmen; PhD from the University of Arizona, 2001, 171 pages http://wwwlib.umi.com/dissertations/fullcit/3016511

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Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to melanoma is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.

Vocabulary Builder Aetiology: Study of the causes of disease. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Kinetic: Pertaining to or producing motion. [EU] Tetracycline: An antibiotic drug used to treat infection. [NIH]

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PART III. APPENDICES

ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients with melanoma and related conditions.

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APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients with melanoma. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications for melanoma. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of melanoma. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

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Your Medications: The Basics153 The Agency for Health Care Research and Quality has published extremely useful guidelines on how you can best participate in the medication aspects of melanoma. Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients with melanoma take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·

Ask about all parts of your treatment, including diet changes, exercise, and medicines.

·

Ask about the risks and benefits of each medicine or other treatment you might receive.

·

Ask how often you or your doctor will check for side effects from a given medication.

Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect how you live or work. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best treatment for you. Do not be afraid to “bother” your doctor with your concerns and questions about medications for melanoma. You can also talk to a nurse or a pharmacist. They can help you better understand your treatment plan. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·

The name of the medicine and what it is supposed to do.

·

How and when to take the medicine, how much to take, and for how long.

·

What food, drinks, other medicines, or activities you should avoid while taking the medicine.

·

What side effects the medicine may have, and what to do if they occur.

·

If you can get a refill, and how often.

153

This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.

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·

About any terms or directions you do not understand.

·

What to do if you miss a dose.

·

If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).

Do not forget to tell your doctor about all the medicines you are currently taking (not just those for melanoma). This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·

Name of medicine

·

Reason taken

·

Dosage

·

Time(s) of day

Also include any over-the-counter medicines, such as: ·

Laxatives

·

Diet pills

·

Vitamins

·

Cold medicine

·

Aspirin or other pain, headache, or fever medicine

·

Cough medicine

·

Allergy relief medicine

·

Antacids

·

Sleeping pills

·

Others (include names)

Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended for melanoma. One such source

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is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the “U.S. Pharmacopeia (USP).” Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database.154 While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopoeia (USP). It is important to read the disclaimer by the USP (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with the treatment of melanoma. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to melanoma: Bleomycin ·

Systemic - U.S. Brands: Blenoxane http://www.nlm.nih.gov/medlineplus/druginfo/bleomycinsyste mic202093.html

Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.

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Carboplatin ·

Systemic - U.S. Brands: Paraplatin http://www.nlm.nih.gov/medlineplus/druginfo/carboplatinsyste mic202115.html

Carmustine ·

Systemic - U.S. Brands: BiCNU http://www.nlm.nih.gov/medlineplus/druginfo/carmustinesyste mic202117.html

Dacarbazine ·

Systemic - U.S. Brands: DTIC-Dome http://www.nlm.nih.gov/medlineplus/druginfo/dacarbazinesyst emic202178.html

Interferons, Alpha ·

Systemic - U.S. Brands: Alferon N; Intron A; Roferon-A http://www.nlm.nih.gov/medlineplus/druginfo/interferonsalpha systemic202299.html

Levamisole ·

Systemic - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/dacarbazinesyst emic202178.html

Melphalan ·

Systemic - U.S. Brands: Alkeran http://www.nlm.nih.gov/medlineplus/druginfo/melphalansyste mic202345.html

Tamoxifen ·

Systemic - U.S. Brands: Nolvadex http://www.nlm.nih.gov/medlineplus/druginfo/tamoxifensyste mic202545.html

Vinblastine ·

Systemic - U.S. Brands: Velban http://www.nlm.nih.gov/medlineplus/druginfo/vinblastinesyste mic202593.html

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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. You may be able to access these sources from your local medical library or your doctor’s office.

Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html.

Mosby’s GenRx Mosby’s GenRx database (also available on CD-Rom and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Information can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html. Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm.

Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. which allows users to download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.

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Drug Development and Approval The following Web sites can be valuable resources when conducting research on the development and approval of new cancer drugs: ·

FDA Home Page: Search for drugs currently in development or those which have been recently approved by the FDA. http://redir.nci.nih.gov/cgibin/redir.pl?section=Cancerinfo&destURI=http://www.fda.gov/

·

Cancer Liaison Program: Answers questions from the public about drug approval processes, cancer clinical trials, and access to investigational therapies. http://redir.nci.nih.gov/cgibin/redir.pl?section=Cancerinfo&destURI=http://www.fda.gov/oashi/c ancer/cancer.html

·

Center for Drug Evaluation and Research http://redir.nci.nih.gov/cgibin/redir.pl?section=Cancerinfo&destURI=http://www.fda.gov/cder/

·

Drug Approvals by Cancer Indications (Alphabetical List) http://redir.nci.nih.gov/cgibin/redir.pl?section=Cancerinfo&destURI=http://www.fda.gov/oashi/c ancer/cdrugalpha.html

·

Drug Approvals by Cancer Indications (Cancer Type) http://redir.nci.nih.gov/cgibin/redir.pl?section=Cancerinfo&destURI=http://www.fda.gov/oashi/c ancer/cdrugind.html

·

Electronic Orange Book of Approved Drug Products http://redir.nci.nih.gov/cgibin/redir.pl?section=Cancerinfo&destURI=http://www.fda.gov/cder/ob /default.htm

·

Guidance Documents for Industry: Contains an archive of documents describing FDA policies on specific topics. http://redir.nci.nih.gov/cgibin/redir.pl?section=Cancerinfo&destURI=http://www.fda.gov/cder/gu idance/index.htm

·

Industry Collaboration: Provides information to industry on the process for getting new drugs into clinical trials. http://ctep.cancer.gov/industry/index.html

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·

Investigator’s Handbook: Provides information to investigators on specific procedures related to clinical trial development. http://ctep.cancer.gov/handbook/index.html

·

Questions and Answers About NCI’s Natural Products Branch: A fact sheet that describes the functions of this branch, which collects and analyzes specimens of plant, marine, and microbial origin for possible anticancer properties. http://cis.nci.nih.gov/fact/7_33.htm

Understanding the Approval Process for New Cancer Drugs155 Since June 1996, about 80 new cancer-related drugs, or new uses for drugs already on the market, have been approved by the U.S. Food and Drug Administration (FDA), the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs before they can go on the market. (The FDA maintains an annotated online list of drugs approved for use with cancer since 1996.) Some of these drugs treat cancer, some alleviate pain and other symptoms, and, in one case, reduce the risk of invasive cancer in people who are considered highrisk. The FDA relied on the results of clinical trials in making every one of these approvals. Without reliable information about a drug’s effects on humans, it would be impossible to approve any drug for widespread use. When considering a new drug, the FDA faces two challenges: ·

First, making sure that the drug is safe and effective before it is made widely available;

·

Second, ensuring that drugs which show promise are made available as quickly as possible to the people they can help.

To deal with these challenges, the FDA maintains a rigorous review process but also has measures in place to make some drugs available in special cases. This aim of this section is to acquaint you with the drug approval process and point you to other resources for learning more about it.

Adapted from the NCI: http://www.cancer.gov/clinical_trials/doc_header.aspx?viewid=d94cbfac-e478-4704-9052d8e8a3372b56.

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The Role of the Federal Drug Administration (FDA) Approval is only one step in the drug development process. In fact, the FDA estimates that, on average, it takes eight and a half years to study and test a new drug before it can be approved for the general public. That includes early laboratory and animal testing, as well as the clinical trials that evaluate the drugs in humans. The FDA plays a key role at three main points in this process: ·

Determining whether or not a new drug shows enough promise to be given to people in clinical trials

·

Once clinical trials begin, deciding whether or not they should continue, based on reports of efficacy and adverse reactions

·

When clinical trials are completed, deciding whether or not the drug can be sold to the public and what its label should say about directions for use, side effects, warnings, and the like.

To make these decisions, the FDA must review studies submitted by the drug’s sponsor (usually the manufacturer), evaluate any adverse reports from preclinical studies and clinical trials (that is, reports of side effects or complications), and review the adequacy of the chemistry and manufacturing. This process is lengthy, but it is meant to ensure that only beneficial drugs with acceptable side effects will make their way into the hands of the public. At the same time, recent legislative mandates and streamlined procedures within the FDA have accelerated the approval of effective drugs, especially for serious illnesses such as cancer. In addition, specific provisions make some drugs available to patients with special needs even before the approval process is complete.

From Lab to Patient Care By law, the Food and Drug Administration (FDA) must review all test results for new drugs to ensure that products are safe and effective for specific uses. “Safe” does not mean that the drug is free of possible adverse side effects; rather, it means that the potential benefits have been determined to outweigh any risks. The testing process begins long before the first person takes the drug, with preliminary research and animal testing. If a drug proves promising in the lab, the drug company or sponsor must apply for FDA approval to test it in clinical trials involving people. For drugs, the application, called an Investigational New Drug (IND)

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Application, is sent through the Center for Drug Evaluation and Research’s (CDER) IND Review Process; for biological agents, the IND is sent to the Center for Biologics Evaluation and Research (CBER). Once the IND is approved by CDER or CBER, clinical trials can begin. If the drug makes it through the clinical trials process—that is, the studies show that it is superior to current drugs—the manufacturer must submit a New Drug Application (NDA) or (for biological agents) a Biologics License Application (BLA) to the FDA. (Biological agents, such as serums, vaccines, and cloned proteins, are manufactured from substances taken from living humans or animals.) This application must include: ·

The exact chemical makeup of the drug or biologic and the mechanisms by which it is effective

·

Results of animal studies

·

Results of clinical trials

·

How the drug or biologic is manufactured, processed, and packaged

·

Quality control standards

·

Samples of the product in the form(s) in which it is to be administered.

Once the FDA receives the NDA or BLA from the manufacturer or developer, the formal New Drug Application Review Process or Biologics/Product License Application Review Process begins. For an overview of the entire process from start to finish, see the CDER’s visual representation of The New Drug Development Process: Steps from Test Tube to New Drug Application Review, which is available for public viewing at the following Web address: http://www.fda.gov/cder/handbook/develop.htm.

Speed versus Safety in the Approval Process The FDA’s current goal is that no more than ten months will pass between the time that a complete application is submitted and the FDA takes action on it. But the process is not always smooth. Sometimes FDA’s external advisory panels call for additional research or data. In other cases, the FDA staff asks for more information or revised studies. Some new drug approvals have taken as little as 42 days; other more difficult NDAs have spent years in the approval process.

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Setting Priorities The order in which NDAs are assessed by the FDA is determined by a classification system designed to give priority to drugs with the greatest potential benefits. All drugs that offer significant medical advances over existing therapies for any disease are considered “priority” drugs in the approval process. NDAs for cancer treatment drugs are reviewed for this status primarily by the Division of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research (CDER). For Biologic License Applications (vaccines, blood products, and medicines made from animal products), the Center for Biologics Evaluation and Research (CBER) provides additional regulation and oversight.

Expert Advice The FDA relies on a system of independent advisory committees, made up of professionals from outside the agency, for expert advice and guidance in making sound decisions about drug approval. Each committee meets as needed to weigh available evidence and assess the safety, effectiveness, and appropriate use of products considered for approval. In addition, these committees provide advice about general criteria for evaluation and scientific issues not related to specific products. The Oncologic Drugs Advisory Committee (ODAC) meets regularly to provide expert advice on cancer-related treatments and preventive drugs. Each committee is composed of representatives from the research science and medical fields. At least one member on every advisory committee must represent the consumer perspective. Final Approval As the FDA looks at all the data submitted and the results of its own review, it applies two benchmark questions to each application for drug approval: ·

Do the results of well-controlled studies provide substantial evidence of effectiveness?

·

Do the results show the product is safe under the conditions of use in the proposed labeling? In this context, “safe” means that potential benefits have been determined to outweigh any risks.

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Continued Vigilance The FDA’s responsibility for new drug treatments does not stop with final approval. The Office of Compliance in the Center for Drug Evaluation and Research (CDER) implements and tracks programs to make sure manufacturers comply with current standards and practice regulations. CDER’s Office of Drug Marketing, Advertising, and Communication monitors new drug advertising to make sure it is truthful and complete. At the Center for Biologic Evaluation and Research, biologics are followed with the same vigilance after approval. And through a system called MedWatch, the FDA gets feedback from health professionals and consumers on how the new drugs are working, any adverse reactions, and potential problems in labeling and dosage. Online FDA Resources The following information from the FDA should help you better understand the drug approval process: ·

Center for Drug Evaluation http://www.fda.gov/cder/handbook

·

From Test Tube to Patient: New Drug Development in the U.S. – a special January 1995 issue of the magazine FDA Consumer: http://www.fda.gov/fdac/special/newdrug/ndd_toc.html

·

Milestones in U.S. Food and Drug Law History: http://www.fda.gov/opacom/backgrounders/miles.html

·

Drug Approvals for Cancer Indications: http://www.fda.gov/oashi/cancer/cdrug.html

and

Research:

Getting Drugs to Patients Who Need Them Clinical trials provide the most important information used by the FDA in determining whether a new drug shows “substantial evidence of effectiveness,” or whether an already-approved drug can be used effectively in new ways (for example, to treat or prevent other types of cancer, or at a different dosage). The FDA must certify that a drug has shown promise in laboratory and animal trials before human testing can begin. The trials process includes three main stages and involves continuous review, which ensures that the sponsor can stop the study early if major problems develop or unexpected levels of treatment benefit are found. As with all clinical trials,

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benefits and risks must be carefully weighed by the researchers conducting the study and the patients who decide to participate. Not everyone is eligible to participate in a clinical trial. Some patients do not fit the exact requirements for studies, some have rare forms of cancer for which only a limited number of studies are underway, and others are too ill to participate. Working with the NCI and other sponsors, the FDA has established special conditions under which a patient and his or her physician can apply to receive cancer drugs that have not yet been through the approval process. In the past, these special case applications for new drugs were grouped under the name “compassionate uses.” More recently, such uses have expanded to include more patients and more categories of investigational drugs.

Access to Investigational Drugs The process of new drug development has many parts. In the United States, until a drug has been approved by the FDA, it can generally be obtained only through several mechanisms: enrollment in a clinical trial studying the drug, an expanded access program or special exemption/compassionate use programs. For more information about investigational drugs, see “Questions and Answers: Access to Investigational Drugs“ at http://www.cancer.gov/cancer_information/doc_img.aspx?viewid=74b62d8 4-e135-451f-9bc9-d54358ede947.

“Group C” Drugs In the 1970s, researchers from the NCI became concerned about the lag between the date when an investigational drug was found to have antitumor activity and the time that drug became available on the market. Working with the FDA, the NCI established the “Group C” classification to allow access to drugs with reproducible activity. Group C drugs are provided to properly trained physicians who have registered using a special form to assure that their patient qualifies under guideline protocols for the drug. Each Group C drug protocol specifies patient eligibility, reporting methodology, and drug use. Not only does Group C designation (now called Group C/Treatment INDs) speed new drugs to patients who need them most, but the process also allows the NCI to gather important information on the safety as well as activity of the drugs in the settings in which they will be most used after final FDA approval. Drugs are placed in the Group C category by agreement between the FDA and the NCI. Group C drugs are

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always provided free of charge, and the Health Care Financing Administration provides coverage for care associated with Group C therapy.

Treatment INDs In 1987, the FDA began authorizing the use of new drugs still in the development process to treat certain seriously ill patients. In these cases, the process is referred to as a treatment investigational new drug application (Treatment IND). Clinical trials of the new drug must already be underway and have demonstrated positive results that are reproducible. The FDA sets guidelines about what constitutes serious and life-threatening illnesses, how much must already be known about a drug’s side effects and benefits, and where physicians can obtain the drug for treatment. For many seriously ill patients, the risks associated with taking a not-yet-completely proven drug are outweighed by the possible benefits.

Accelerated Approval “Accelerated approval” is the short-hand term for the FDA’s new review system which, in the 1990s, has been used to ensure rapid approval while at the same time putting new safeguards into place. Accelerated approval is based on “surrogate endpoint” judgments: FDA can grant marketing approval to drugs and treatments that, according to certain indicators, prove they are likely to have beneficial effects on a disease or condition, even before such direct benefits have been shown clinically. Accelerated approval does NOT mean that additional clinical trials are not needed or that FDA stops gathering information about the effects of the drug; a follow-up study is required to demonstrate activity by more conventional endpoints.

Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients with melanoma--not because they are used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat melanoma or potentially create deleterious side effects in patients with melanoma. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments.

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Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it’s especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take. The package insert provides more information about potential drug interactions.

A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients with melanoma. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with melanoma. The FDA warns patients to watch out for156: ·

Secret formulas (real scientists share what they know)

·

Amazing breakthroughs or miracle cures (real breakthroughs don’t happen very often; when they do, real scientists do not call them amazing or miracles)

156

This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.

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·

Quick, painless, or guaranteed cures

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If it sounds too good to be true, it probably isn’t true.

If you have any questions about any kind of medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

Antifolate Drugs in Cancer Therapy (Cancer Drug Discovery and Development) by Ann L. Jackman (Editor); Hardcover: 480 pages; (March 1999), Humana Press; ISBN: 0896035964; http://www.amazon.com/exec/obidos/ASIN/0896035964/icongroupinterna

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Consumers Guide to Cancer Drugs by Gail M. Wilkes, et al; Paperback 448 pages, 1st edition (January 15, 2000), Jones & Bartlett Publishing; ISBN: 0763711705; http://www.amazon.com/exec/obidos/ASIN/0763711705/icongroupinterna

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Patient Education Guide to Oncology Drugs (Book with CD-ROM) by Gail M. Wilkes, et al; CD-ROM - 447 pages, 1st edition (January 15, 2000), Jones & Bartlett Publishing; ISBN: 076371173X; http://www.amazon.com/exec/obidos/ASIN/076371173X/icongroupinterna

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The Role of Multiple Intensification in Medical Oncology by M. S. Aapro (Editor), D. Maraninchi (Editor); Hardcover (June 1998), Springer Verlag; ISBN: 3540635432; http://www.amazon.com/exec/obidos/ASIN/3540635432/icongroupinterna

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Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Carboplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH]

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APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview157 Research indicates that the use of complementary and alternative therapies is increasing. A large-scale study published in the November 11, 1998, issue of the Journal of the American Medical Association found that CAM use among the general public increased from 34 percent in 1990 to 42 percent in 1997. Several surveys of CAM use by cancer patients have been conducted with small numbers of patients. One study published in the February 2000 issue of the journal Cancer reported that 37 percent of 46 patients with prostate cancer used one or more CAM therapies as part of their cancer treatment. These therapies included herbal remedies, old-time remedies, vitamins, and special diets. A larger study of CAM use in patients with different types of cancer was published in the July 2000 issue of the Journal of Clinical Oncology . That study found that 83 percent of 453 cancer patients had used at least one CAM therapy as part of their cancer treatment. The study included CAM therapies such as special diets, psychotherapy, spiritual practices, and vitamin supplements. When psychotherapy and spiritual practices were excluded, 69 percent of patients had used at least one CAM therapy in their cancer treatment. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to melanoma. Finally, at the conclusion of this chapter, we will provide a list of readings on melanoma from various authors. We will begin, however, with the National Center for

157Adapted

from the NCI: http://cis.nci.nih.gov/fact/9_14.htm.

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Complementary and Alternative Medicine’s (NCCAM) overview of complementary and alternative medicine.

What Is CAM?158 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also known as “preventive,” which means that the practitioner educates and treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture. Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. 158

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.

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The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.

What Are the Domains of Alternative Medicine?159 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each. Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India’s traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic

159

Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.

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treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body’s defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology. Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind’s capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.

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Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine’s use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.

Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body’s systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues. Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch.

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Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient’s recovery and that healing is promoted when the body’s energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields. Research indicates that the use of complementary and alternative therapies is increasing. A large-scale study published in the November 11, 1998, issue of the Journal of the American Medical Association found that CAM use among the general public increased from 34 percent in 1990 to 42 percent in 1997. Several surveys of CAM use by cancer patients have been conducted with small numbers of patients. One study published in the February 2000 issue of the journal Cancer reported that 37 percent of 46 patients with prostate cancer used one or more CAM therapies as part of their cancer treatment. These therapies included herbal remedies, old-time remedies, vitamins, and special diets. A larger study of CAM use in patients with different types of cancer was published in the July 2000 issue of the Journal of Clinical Oncology . That study found that 83 percent of 453 cancer patients had used at least one CAM therapy as part of their cancer treatment. The study included CAM therapies such as special diets, psychotherapy, spiritual practices, and vitamin supplements. When psychotherapy and spiritual practices were excluded, 69 percent of patients had used at least one CAM therapy in their cancer treatment.

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How Are Complementary and Alternative Approaches Evaluated?160 It is important that the same scientific evaluation which is used to assess conventional approaches be used to evaluate complementary and alternative therapies. A number of medical centers are evaluating complementary and alternative therapies by developing clinical trials (research studies with people) to test them. Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a rigorous scientific process, including clinical trials with large numbers of patients. Often, less is known about the safety and effectiveness of complementary and alternative methods. Some of these complementary and alternative therapies have not undergone rigorous evaluation. Others, once considered unorthodox, are finding a place in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) Consensus Conference in November 1997, acupuncture has been found to be effective in the management of chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery. Some approaches, such as laetrile, have been studied and found ineffective or potentially harmful.

NCI-Sponsored Clinical Trials in Complementary and Alternative Medicine The NCI is currently sponsoring several clinical trials (research studies with patients) that study complementary and alternative treatments for cancer. Current trials include enzyme therapy with nutritional support for the treatment of inoperable pancreatic cancer, shark cartilage therapy for the treatment of non-small cell lung cancer, and studies of the effects of diet on prostate and breast cancers. Some of these trials compare alternative therapies with conventional treatments, while others study the effects of complementary approaches used in addition to conventional treatments. Patients who are interested in taking part in these or any clinical trials should talk with their doctor. More information about clinical trials sponsored by the NCI can be obtained from NCCAM (http://nccam.nih.gov, 1-888-644-6226), OCCAM

160Adapted

from the NCI: http://cis.nci.nih.gov/fact/9_14.htm

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(http://occam.nci.nih.gov), and the NCI’s Cancer Information Service (CIS) (http://cis.nci.nih.gov, 1-800-4-CANCER).

Questions to Ask Your Healthcare Provider about CAM When considering complementary and alternative therapies, ask your healthcare provider the following questions: ·

What benefits can be expected from this therapy?

·

What are the risks associated with this therapy?

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Do the known benefits outweigh the risks?

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What side effects can be expected?

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Will the therapy interfere with conventional treatment?

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Is this therapy part of a clinical trial? If so, who is sponsoring the trial?

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Will the therapy be covered by health insurance?

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How can patients and their health care providers learn more about complementary and alternative therapies?

Finding CAM References on Melanoma Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for melanoma. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov) has created a link to the National Library of Medicine’s databases to allow patients to search for articles that specifically relate to melanoma and complementary medicine. To search the database, go to the following Web site: www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “melanoma” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of

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complementary and alternative medicine (CAM) that are related to melanoma: ·

(+)-Tiliarine, a selective in vitro inhibitor of human melanoma cells. Author(s): Seal T, Mukherjee B. Source: Phytotherapy Research : Ptr. 2002 September; 16(6): 596-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12237824&dopt=Abstract

·

12(S)-hydroxyeicosatetraenoic acid increases the actin microfilament content in B16a melanoma cells: a protein kinase-dependent process. Author(s): Rice RL, Tang DG, Haddad M, Honn KV, Taylor JD. Source: International Journal of Cancer. Journal International Du Cancer. 1998 July 17; 77(2): 271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9650564&dopt=Abstract

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A clinical trial of intravenous vinorelbine tartrate plus tamoxifen in the treatment of patients with advanced malignant melanoma. Author(s): Feun LG, Savaraj N, Hurley J, Marini A, Lai S. Source: Cancer. 2000 February 1; 88(3): 584-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10649251&dopt=Abstract

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A factual, not arbitrary, basis for choice of resection margins in melanoma. Author(s): Piepkorn M, Barnhill RL. Source: Archives of Dermatology. 1996 July; 132(7): 811-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8678574&dopt=Abstract

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A novel gelatinolytic enzyme secreted by amelanotic cells isolated from B16 melanoma cell line. Author(s): Kobayashi T, Hayashi A, Ura-Ishikou A, Tajima S, Nishikawa T. Source: Cancer Letters. 1994 October 14; 85(2): 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7954332&dopt=Abstract

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A structured psychiatric intervention for patients with malignant melanoma: Fawzy et al. (1990b). Author(s): Payne D.

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Source: Advances in Mind-Body Medicine. 2001 Winter; 17(1): 21-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11270055&dopt=Abstract ·

Acceptance by Swedish users of a multimedia program for primary and secondary prevention of malignant melanoma. Author(s): Lindholm LH, Isacsson A, Slaug B, Moller TR. Source: J Cancer Educ. 1998 Winter; 13(4): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9883779&dopt=Abstract

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Accuracy of presumed uveal melanoma diagnosis before alternative therapy. Author(s): Char DH, Miller T. Source: The British Journal of Ophthalmology. 1995 July; 79(7): 692-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7662638&dopt=Abstract

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Acquisition of multiple copies of a mutant topoisomerase IIalpha allele by chromosome 17 aneuploidy is associated with etoposide resistance in human melanoma cell lines. Author(s): Campain JA, Slovak ML, Schoenlein PV, Popescu NC, Gottesman MM, Pastan I. Source: Somatic Cell and Molecular Genetics. 1995 November; 21(6): 45171. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8600572&dopt=Abstract

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Activity of extracts of Kigelia pinnata against melanoma and renal carcinoma cell lines. Author(s): Houghton PJ, Photiou A, Uddin S, Shah P, Browning M, Jackson SJ, Retsas S. Source: Planta Medica. 1994 October; 60(5): 430-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7997471&dopt=Abstract

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Adenovirus infection enhances killing of melanoma cells by a mitotoxin. Author(s): Satyamoorthy K, Soballe PW, Soans F, Herlyn M.

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Source: Cancer Research. 1997 May 15; 57(10): 1873-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9157978&dopt=Abstract ·

Adjuvant regional isolated perfusion with melphalan for patients with Clark V melanoma of the extremities. Author(s): Vrouenraets BC, Kroon BB, Klaase JM, Van Geel BN, Eggermont AM, Franklin HR. Source: Journal of Surgical Oncology. 1993 April; 52(4): 249-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8468989&dopt=Abstract

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Adjuvant therapy for cutaneous malignant melanoma. Author(s): Demierre MF, Koh HK. Source: Journal of the American Academy of Dermatology. 1997 May; 36(5 Pt 1): 747-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9146538&dopt=Abstract

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Adjuvant therapy of malignant melanoma. Author(s): Molife R, Hancock BW. Source: Critical Reviews in Oncology/Hematology. 2002 October; 44(1): 81-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12399001&dopt=Abstract

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Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania and bipolar syndromes. Author(s): Greenberg DB, Jonasch E, Gadd MA, Ryan BF, Everett JR, Sober AJ, Mihm MA, Tanabe KK, Ott M, Haluska FG. Source: Cancer. 2000 July 15; 89(2): 356-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10918166&dopt=Abstract

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Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. Author(s): Lissoni P, Brivio O, Brivio F, Barni S, Tancini G, Crippa D, Meregalli S. Source: Journal of Pineal Research. 1996 November; 21(4): 239-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8989723&dopt=Abstract

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Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells. Author(s): Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, Greenberg PD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 11 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12427970&dopt=Abstract

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AgNOR values in Callender histopathological types of malignant uveal melanomas. Author(s): Mera M. Source: Rom J Morphol Embryol. 1995 July-December; 41(3-4): 125-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8772368&dopt=Abstract

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Alterations of DNA repair in melanoma cell lines resistant to cisplatin, fotemustine, or etoposide. Author(s): Runger TM, Emmert S, Schadendorf D, Diem C, Epe B, Hellfritsch D. Source: The Journal of Investigative Dermatology. 2000 January; 114(1): 34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10620112&dopt=Abstract

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Anti-B16-F10 melanoma activity of a basic fibroblast growth factorsaporin mitotoxin. Author(s): Ying W, Martineau D, Beitz J, Lappi DA, Baird A. Source: Cancer. 1994 August 1; 74(3): 848-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8039113&dopt=Abstract

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Anti-tumor effect of electrotherapy alone or in combination with interleukin-2 in mice with sarcoma and melanoma tumors. Author(s): Sersa G, Miklavcic D, Batista U, Novakovic S, Bobanovic F, Vodovnik L. Source: Anti-Cancer Drugs. 1992 June; 3(3): 253-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1525406&dopt=Abstract

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Apoptotic effects of ginsenoside Rh2 on human malignant melanoma A375-S2 cells. Author(s): Fei XF, Wang BX, Tashiro S, Li TJ, Ma JS, Ikejima T. Source: Acta Pharmacologica Sinica. 2002 April; 23(4): 315-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11931705&dopt=Abstract

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Attitude toward alternative therapy, compliance with standard treatment, and need for emotional support in patients with melanoma. Author(s): Sollner W, Zingg-Schir M, Rumpold G, Fritsch P. Source: Archives of Dermatology. 1997 March; 133(3): 316-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9080891&dopt=Abstract

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Ayurvedic agents produce differential effects on murine and human melanoma cells in vitro. Author(s): Prasad ML, Parry P, Chan C. Source: Nutrition and Cancer. 1993; 20(1): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8415133&dopt=Abstract

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Benzo-gamma-pyrone analogues of geiparvarin: synthesis and biological evaluation against B16 melanoma cells. Author(s): Valenti P, Da Re P, Rampa A, Montanari P, Carrara M, Cima L. Source: Anti-Cancer Drug Design. 1993 October; 8(5): 349-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8251042&dopt=Abstract

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Binding of mistletoe lectins to cutaneous malignant melanoma: implications for prognosis and therapy. Author(s): Thies A, Pfuller U, Schachner M, Horny HP, Molls I, Schumacher U. Source: Anticancer Res. 2001 July-August; 21(4B): 2883-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11712781&dopt=Abstract

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Biotransformation of the antimelanoma agent betulinic acid by Bacillus megaterium ATCC 13368. Author(s): Chatterjee P, Kouzi SA, Pezzuto JM, Hamann MT.

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Source: Applied and Environmental Microbiology. 2000 September; 66(9): 3850-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10966400&dopt=Abstract ·

Cell differentiation and cell-cycle alterations by tyrosine kinase inhibitors in human melanoma cells. Author(s): Hartmann RR, Rimoldi D, Lejeune FJ, Carrel S. Source: Melanoma Research. 1997 August; 7 Suppl 2: S27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9578414&dopt=Abstract

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Cell-killing by paclitaxel in a metastatic murine melanoma cell line is mediated by extensive telomere erosion with no decrease in telomerase activity. Author(s): Multani AS, Li C, Ozen M, Imam AS, Wallace S, Pathak S. Source: Oncol Rep. 1999 January-February; 6(1): 39-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9864398&dopt=Abstract

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Cellular resistance to the antimelanoma immunotoxin ZME-gelonin and strategies to target resistant cells. Author(s): Rosenblum MG, Cheung L, Kim SK, Mujoo K, Donato NJ, Murray JL. Source: Cancer Immunology, Immunotherapy : Cii. 1996 February; 42(2): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8620520&dopt=Abstract

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Changes in immunological parameters after combination adjuvant therapy with intravenous DTIC, ACNU, and VCR, and local injection of IFN-beta (DAV + IFN-beta therapy) into malignant melanoma. Author(s): Umeda T, Aoki K, Yokoyama A, Ohara H, Hayashi O, Tanaka K, Nishioka K. Source: J Dermatol. 1998 September; 25(9): 569-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9798342&dopt=Abstract

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Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. Author(s): Cole DJ, Weil DP, Shilyansky J, Custer M, Kawakami Y, Rosenberg SA, Nishimura MI.

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Source: Cancer Research. 1995 February 15; 55(4): 748-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7531614&dopt=Abstract ·

Chemotherapy of metastatic melanoma. Author(s): Cohen SM. Source: The Mount Sinai Journal of Medicine, New York. 1992 May; 59(3): 220-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1351249&dopt=Abstract

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Clinical and immunologic effects of T-activin therapy in early stage melanoma patients. Author(s): Stanojevic-Bakic N, Milosevic D, Vuckovic-Dekic L, Sasic M, Markovic L. Source: Neoplasma. 1996; 43(4): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8931749&dopt=Abstract

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Clinical experience with high-dose tumor necrosis factor alpha in regional therapy of advanced melanoma. Author(s): Lejeune F, Lienard D, Eggermont A, Schraffordt Koops H, Kroon B, Gerain J, Rosenkaimer F, Schmitz P. Source: Circ Shock. 1994 August; 43(4): 191-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7895325&dopt=Abstract

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Cloning and characterization of anti-cathepsin L single chain variable fragment whose expression inhibits procathepsin L secretion in human melanoma cells. Author(s): Guillaume-Rousselet N, Jean D, Frade R. Source: The Biochemical Journal. 2002 October 1; 367(Pt 1): 219-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12241546&dopt=Abstract

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Comparative cytotoxicity and pharmacokinetics of antimelanoma immunotoxins containing either natural or recombinant gelonin. Author(s): Rosenblum MG, Marks JW, Cheung LH. Source: Cancer Chemotherapy and Pharmacology. 1999; 44(4): 343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10447583&dopt=Abstract

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Comparison of apoptotic, necrotic and clonogenic cell death and inhibition of cell growth following camptothecin and X-radiation treatment in a human melanoma and a human fibroblast cell line. Author(s): Quto b SS, Ng CE. Source: Cancer Chemotherapy and Pharmacology. 2002 February; 49(2): 167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11862432&dopt=Abstract

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Comparison of the effects of Viscum album lectin ML-1 and fresh plant extract (Isorel) on the cell growth in vitro and tumorigenicity of melanoma B16F10. Author(s): Zarkovic N, Kalisnik T, Loncaric I, Borovic S, Mang S, Kissel D, Konitzer M, Jurin M, Grainza S. Source: Cancer Biotherapy & Radiopharmaceuticals. 1998 April; 13(2): 121-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10850348&dopt=Abstract

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Cutaneous malignant melanoma and sun exposure in Spain. Author(s): Espinosa Arranz J, Sanchez Hernandez JJ, Bravo Fernandez P, Gonzalez-Baron M, Zamora Aunon P, Espinosa Arranz E, Jalon Lopez JI, Ordonez Gallego A. Source: Melanoma Research. 1999 April; 9(2): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10380943&dopt=Abstract

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Cutaneous malignant melanoma in children. Author(s): Vandeweyer E, Sales F, Deraemaecker R. Source: European Journal of Pediatrics. 2000 August; 159(8): 582-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10968235&dopt=Abstract

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Cytotoxic interactions of Zn2+ in vitro: melanoma cells are more susceptible than melanocytes. Author(s): Borovansky J, Blasko M, Siracky J, Schothorst AA, Smit NP, Pavel S. Source: Melanoma Research. 1997 December; 7(6): 449-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9464616&dopt=Abstract

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Detection of P-glycoprotein in the Golgi apparatus of drug-untreated human melanoma cells. Author(s): Molinari A, Calcabrini A, Meschini S, Stringaro A, Del Bufalo D, Cianfriglia M, Arancia G. Source: International Journal of Cancer. Journal International Du Cancer. 1998 March 16; 75(6): 885-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9506534&dopt=Abstract

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DFNA5 (ICERE-1) contributes to acquired etoposide resistance in melanoma cells. Author(s): Lage H, Helmbach H, Grottke C, Dietel M, Schadendorf D. Source: Febs Letters. 2001 April 6; 494(1-2): 54-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11297734&dopt=Abstract

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Dietary supplementation of selenomethionine reduces metastasis of melanoma cells in mice. Author(s): Yan L, Yee JA, Li D, McGuire MH, Graef GL. Source: Anticancer Res. 1999 March-April; 19(2A): 1337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10368696&dopt=Abstract

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Differential response of human melanoma and Ehrlich ascites cells in vitro to the ribosome-inactivating protein luffin. Author(s): Poma A, Miranda M, Spano L. Source: Melanoma Research. 1998 October; 8(5): 465-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9835461&dopt=Abstract

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Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Author(s): Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CW, Fong HH, Kinghorn AD, Brown DM, et al. Source: Nature Medicine. 1995 October; 1(10): 1046-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7489361&dopt=Abstract

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Distinct Chk2 activation pathways are triggered by genistein and DNA-damaging agents in human melanoma cells. Author(s): Darbon JM, Penary M, Escalas N, Casagrande F, GoubinGramatica F, Baudouin C, Ducommun B.

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Source: The Journal of Biological Chemistry. 2000 May 19; 275(20): 153639. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10809772&dopt=Abstract ·

Diverse activity of sc-RIP saporin 6 on primary and metastatic melanoma cells in vitro. Author(s): Gasperi-Campani A, Musa AR, Roncuzzi L. Source: Melanoma Research. 1993 October; 3(5): 363-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8292894&dopt=Abstract

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DNA topoisomerase I content of a pair of human melanoma cell lines with very different radiosensitivities correlates with their in vitro sensitivities to camptothecin. Author(s): Ng CE, Cybulski SE, Bussey AM, Aubin RA, Raaphorst GP. Source: Anticancer Res. 1998 July-August; 18(4C): 3119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9713520&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.thedacare.org/healthnotes/

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Open Directory Project: http://dmoz.org/Health/Alternative/

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TPN.com: http://www.tnp.com/

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

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·

WellNet: http://www.wellnet.ca/herbsa-c.htm

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

The following is a specific Web list relating to melanoma; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·

General Overview Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cancer_Breast.ht m Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cancer_Diet.htm Cancer, Skin Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Can cerSkincc.html Cervical Dysplasia Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Cer vicalDysplasiacc.html Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cancer_Colon.htm

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Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cancer_Lung.htm Pap Smear, Abnormal Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Cer vicalDysplasiacc.html Photodermatitis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Skin DisordersPhotodermatitiscc.html Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Cancer_Prostate.h tm Skin Cancer Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Can cerSkincc.html Skin Disorders, Photodermatitis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Skin DisordersPhotodermatitiscc.html

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Sunburn Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Skin DisordersPhotodermatitiscc.html Uveitis Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Uve itiscc.html Vitiligo Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Vitiligo.htm ·

Herbs and Supplements Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Brahmi Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/GotuKol ach.html Bryonia Bryony Alternative names: Bryony; Bryonia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/

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Centella Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/GotuKol ach.html Centella asiatica Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/GotuKol ach.html Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Chemotherapy.htm Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Cyclophosphamide.h tm Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Docetaxel.htm

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Flaxseed Alternative names: Linum usitatissimum, Linseed Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Flaxseed ch.html Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Fluorouracil.htm Gamma-Linolenic Acid (GLA) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/G ammaLinolenicAcidGLAcs.html GLA Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/G ammaLinolenicAcidGLAcs.html Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Gotu Kola Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/GotuKol ach.html

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Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Herb/Green_Tea.htm Hydrocotyle Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/GotuKol ach.html Indian Pennywort Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/GotuKol ach.html Linseed Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Flaxseed ch.html Linum usitatissimum Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Flaxseed ch.html Luffa Alternative names: Luffa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/

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Marsh Pennywort Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/GotuKol ach.html Melatonin Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Melatonin.htm Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Methotrexate.htm Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Paclitaxel.htm Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Phenylalanine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/P henylalaninecs.html Phytolacca Alternative names: Poke root, Endod; Phytolacca dodecandra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/

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Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Tocotrienols Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Tocotrienols.htm Turmeric Alternative names: Curcuma longa Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Herb/Turmeric.htm Tyrosine Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/T yrosinecs.html Yucca Alternative names: Yucca schidigera , Yucca spp. Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Herb/Yucca.htm Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at: www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site

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provides a general overview of various topics and can lead to a number of general sources. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Alternative Medicine Definitive Guide to Cancer by W. John Diamond, et al; Hardcover - 1120 pages Package edition (March 18, 1997), Alternativemedicine.Com Books; ISBN: 1887299017; http://www.amazon.com/exec/obidos/ASIN/1887299017/icongroupinterna · Beating Cancer With Nutrition - Revised by Patrick Quillin, Noreen Quillin (Contributor); Paperback - 352 pages; Book & CD edition (January 1, 2001), Bookworld Services; ISBN: 0963837281; http://www.amazon.com/exec/obidos/ASIN/0963837281/icongroupinterna · Cancer: Increasing Your Odds for Survival - A Resource Guide for Integrating Mainstream, Alternative and Complementary Therapies by David Bognar, Walter Cronkite; Paperback (August 1998), Hunter House; ISBN: 0897932471; http://www.amazon.com/exec/obidos/ASIN/0897932471/icongroupinterna · Choices in Healing by Michael Lerner; Paperback - 696 pages; (February 28, 1996), MIT Press; ISBN: 0262621045; http://www.amazon.com/exec/obidos/ASIN/0262621045/icongroupinterna · The Gerson Therapy: The Amazing Nutritional Program for Cancer and Other Illnesses by Charlotte Gerson, Morton Walker, D.P.M.; Paperback 448 pages (October 2001), Kensington Publishing Corp.; ISBN: 1575666286; http://www.amazon.com/exec/obidos/ASIN/1575666286/icongroupinterna · Natural Compounds in Cancer Therapy by John C. Boik; Paperback - 520 pages (March 2001), Oregon Medical Press; ISBN: 0964828014; http://www.amazon.com/exec/obidos/ASIN/0964828014/icongroupinterna · There’s No Place Like Hope: A Guide to Beating Cancer in Mind-Sized Bites by Vickie Girard, Dan Zadra (Editor); Hardcover - 161 pages (April 2001), Compendium Inc.; ISBN: 1888387416; http://www.amazon.com/exec/obidos/ASIN/1888387416/icongroupinterna · Your Life in Your Hands by Jane A. Plant, Ph.D; Hardcover - 272 pages (December 13, 2000), St. Martins Press (Trade); ISBN: 0312275617; http://www.amazon.com/exec/obidos/ASIN/0312275617/icongroupinterna

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For additional information on complementary and alternative medicine, ask your doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218

Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Ascites: Abnormal buildup of fluid in the abdomen. [NIH] Camptothecin: An anticancer drug that belongs to the family of drugs called topoisomerase inhibitors. [NIH] Cyclophosphamide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Etoposide: An anticancer drug that is a podophyllotoxin derivative and belongs to the family of drugs called mitotic inhibitors. [NIH] Ginseng: An herb with a root that has been used in some cultures to treat certain medical problems. It may have anticancer effects. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH] Inoperable: Not suitable to be operated upon. [EU] Lectins: Protein or glycoprotein substances, usually of plant origin, that bind to sugar moieties in cell walls or membranes and thereby change the physiology of the membrane to cause agglutination, mitosis, or other biochemical changes in the cell. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU]

Methotrexate: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH]

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Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pharmacokinetics: The activity of drugs in the body over a period of time, including the processes by which drugs are absorbed, distributed in the body, localized in the tissues, and excreted. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH]

Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the diagnosis and treatment of cancer and in pain management of bone metastases. Also called radioactive drugs. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Supplementation: Adding nutrients to the diet. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Viscum: A genus of Old World parasitic plants of the Loranthaceae. Viscum album and Phorandendron flavescens were formerly used as emmenagogues, cardiac stimulants, and vasodilators. The plants contain toxins, lectins, tyramine, phenethylamines, and other useful or dangerous compounds. [NIH]

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APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to patients’ health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements to patients with melanoma. Any dietary recommendation is based on a patient’s age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients with melanoma may be given different recommendations. Some recommendations may be directly related to melanoma, while others may be more related to the patient’s general health. These recommendations, themselves, may differ from what official sources recommend for the average person. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of melanoma. We will then show you how to find studies dedicated specifically to nutrition and melanoma.

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Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and (6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·

Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.

·

Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.

·

Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.

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Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.

Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·

Vitamin A is important to the health of your eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.

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Vitamin B1, also known as thiamine, is important for your nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.

·

Vitamin B2, also known as riboflavin, is important for your nervous system and muscles, but is also involved in the release of proteins from

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nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs. ·

Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains

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Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.

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Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.

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Vitamin C allows the body’s immune system to fight various diseases, strengthens body tissue, and improves the body’s use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.

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Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.

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Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.

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Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.

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Folic Acid maintains healthy cells and blood and, when taken by a pregnant woman, can prevent her fetus from developing neural tube defects; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.

It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·

Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.

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Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.

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·

Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.

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Iodine helps regulate the body’s use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.

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Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.

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Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.

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Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.

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Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.

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Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.

The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, your doctor may encourage deviations from the average official recommendation based on your specific condition. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/labcons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:161 ·

DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.

·

DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.

161

Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.

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·

RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.”

·

RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?162

Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. The Office of Dietary Supplements (ODS) of the National Institutes of Health is the official agency of the United States which has the expressed goal of acquiring “new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.”163 According to the ODS, dietary supplements can have an important impact on the prevention and management of disease and on the maintenance of health.164 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 163 Contact: The Office of Dietary Supplements, National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: (301) 435-2920, Fax: (301) 480-1845, E-mail: [email protected]. 164 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 162

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the use of plant products, in particular, has a long tradition. However, the overwhelming majority of supplements have not been studied scientifically. To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of Dietary Supplements National Institutes of Health Building 31, Room 1B29 31 Center Drive, MSC 2086 Bethesda, Maryland 20892-2086 Tel: (301) 435-2920 Fax: (301) 480-1845 E-mail: [email protected]

Finding Studies on Melanoma The NIH maintains an office dedicated to patient nutrition and diet. The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.165 IBIDS is available to the public free of charge through the ODS Internet page: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

165

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periodically as this database is frequently updated. More studies can be found by searching the Full IBIDS Database. Healthcare professionals and researchers generally use the third option, which lists peer-reviewed citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “melanoma” (or synonyms) into the search box. To narrow the search, you can also select the “Title” field. The following information is typical of that found when using the “Full IBIDS Database” when searching using “melanoma” (or a synonym): ·

5-S-cysteinyldopa as diagnostic tumor marker for uveal malignant melanoma. Author(s): Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan. Source: Goto, H Usui, M Wakamatsu, K Ito, S Jpn-J-Ophthalmol. 2001 Sep-October; 45(5): 538-42 0021-5155

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A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma. Author(s): Division of Medical Oncology, University of Colorado Cancer Center, Denver 80262, USA. Source: Gibbs, P Iannucci, A Becker, M Allen, J O'Driscoll, M McDowell, K Williams, P Rosse, P Murphy, J Gonzalez, R Melanoma-Res. 2000 April; 10(2): 171-9 0960-8931

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A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumour tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-borono-2[18F]fluoro-L-phenylalanine. Author(s): Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. Source: Ishiwata, K Shiono, M Kubota, K Yoshino, K Hatazawa, J Ido, T Honda, C Ichihashi, M Mishima, Y Melanoma-Res. 1992 September; 2(3): 171-9 0960-8931

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Adjuvant therapy of malignant melanoma: is there a choice? Author(s): Melanoma Unit, Department of Medical Oncology, Charing Cross Hospital, Fulham Palace Road, W6 8RF, London, UK. [email protected] Source: Retsas, S Crit-Rev-Oncol-Hematol. 2001 November; 40(2): 187-93 1040-8428

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·

Advantages of concurrent biochemotherapy modified by decrescendo interleukin-2, granulocyte colony-stimulating factor, and tamoxifen for patients with metastatic melanoma. Author(s): Division of Medical and Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA. o'[email protected] Source: O'Day, S J Gammon, G Boasberg, P D Martin, M A Kristedja, T S Guo, M Stern, S Edwards, S Fournier, P Weisberg, M Cannon, M Fawzy, N W Johnson, T D Essner, R Foshag, L J Morton, D L J-Clin-Oncol. 1999 September; 17(9): 2752-61 0732-183X

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An association of zinc with omega-6-fatty acid and cAMP synthesis in melanoma cells. Source: Skeef, N.S. Duncan, J.R. Trace elements in man and animals 6 / edited by Lucille S. Hurley, ... [et al.]. New York : Plenum Press, c1988. page 367-368. ISBN: 0306430045

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An inhibitor of stress-activated MAP-kinases reduces invasion and MMP-2 expression of malignant melanoma cells. Author(s): Institute of Pathology, Charite Hospital, Berlin, Germany. Source: Denkert, Carsten Siegert, Antje Leclere, Anja Turzynski, Andreas Hauptmann, Steffen Clin-Exp-Metastasis. 2002; 19(1): 79-85 0262-0898

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Antimelanoma monoclonal antibody-ricin A chain immunoconjugate (XMMME-001-RTA) plus cyclophosphamide in the treatment of metastatic malignant melanoma: results of a phase II trial. Author(s): Kaplan Cancer Center, New York University Medical Center, New York, New York 10016. Source: Oratz, R Speyer, J L Wernz, J C Hochster, H Meyers, M Mischak, R Spitler, L E J-Biol-Response-Mod. 1990 August; 9(4): 345-54 0732-6580

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Association of genomic imbalances with resistance to therapeutic drugs in human melanoma cell lines. Author(s): Abteilung Organisation komplexer Genome, Deutsches Krebsforschungszentrum, Heidelberg, Germany. Source: Nessling, M Kern, M A Schadendorf, D Lichter, P Cytogenet-CellGenet. 1999; 87(3-4): 286-90 0301-0171

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Atypical protein kinase Czeta suppresses migration of mouse melanoma cells. Author(s): Department of Chemistry and Biochemistry, Queens College of the City University of New York, Flushing, New York 11367, USA. Source: Sanz Navares, E Fernandez, N Kazanietz, M G Rotenberg, S A Cell-Growth-Differ. 2001 October; 12(10): 517-24 1044-9523

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·

Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes. Author(s): Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, 14195, Berlin, Germany. Source: Raisova, Monika Goltz, Gerit Bektas, Meryem Bielawska, Alicja Riebeling, Christian Hossini, Amir M Eberle, Jurgen Hannun, Yusuf A Orfanos, Constantin E Geilen, Christoph C FEBS-Lett. 2002 April 10; 516(1-3): 47-52 0014-5793

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Beta-thujaplicin zinc chelate induces apoptosis in mouse high metastatic melanoma B16BL6 cells. Author(s): Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, Japan. Source: Miyamoto, D Endo, N Oku, N Arima, Y Suzuki, T Suzuki, Y BiolPharm-Bull. 1998 December; 21(12): 1258-62 0918-6158

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Changes in immunological parameters after combination adjuvant therapy with intravenous DTIC, ACNU, and VCR, and local injection of IFN-beta (DAV + IFN-beta therapy) into malignant melanoma. Author(s): Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Japan. Source: Umeda, T Aoki, K Yokoyama, A Ohara, H Hayashi, O Tanaka, K Nishioka, K J-Dermatol. 1998 September; 25(9): 569-72 0385-2407

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Characterization of melanoma associated spongiform scleropathy. Author(s): Eye Pathology Institute, University of Copenhagen, Denmark. Source: Alyahya, Ghassan Ayish Heegaard, Steffen Prause, January Ulrik Acta-Ophthalmol-Scand. 2002 June; 80(3): 322-6 1395-3907

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Chemotherapy-induced apoptosis in melanoma cells is p53 dependent. Author(s): Department of Medicine, University of British Columbia and the Vancouver Hospital and Health Science Centre, Canada. Source: Li, G Tang, L Zhou, X Tron, V Ho, V Melanoma-Res. 1998 February; 8(1): 17-23 0960-8931

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Circuit and protocol for hypoxic hyperthermic isolated limb perfusion to treat malignant melanoma. Author(s): Department of Cardiothoracic Surgery-Perfusion, Waikato Hospital, Hamilton, New Zealand. [email protected] Source: Innet, L M Haripershad, V Van Den Berg, J Cooper, L Perfusion. 2001 July; 16(4): 325-30 0267-6591

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Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or cytosine arabinoside. Author(s): Department of Pathology, Institute of Ophthalmology, University College London, UK.

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Source: Neale, M H Myatt, N Cree, I A Kurbacher, C M Foss, A J Hungerford, J L Plowman, P N Br-J-Cancer. 1999 March; 79(9-10): 1487-93 0007-0920 ·

Combination chemotherapy with vinblastine, BCNU and cisplatin in advanced malignant melanoma. Author(s): Division of Medical Oncology A, National Tumor Institute, Naples, Italy. Source: Comella, G Daponte, A Comella, P Casaretti, R Iervolino, V Santillo, G Zarrilli, D Tumori. 1991 June 30; 77(3): 216-8 0300-8916

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Comparison of apoptotic, necrotic and clonogenic cell death and inhibition of cell growth following camptothecin and X-radiation treatment in a human melanoma and a human fibroblast cell line. Author(s): Ottawa Regional Cancer Centre, Ottawa, ON, K1H 1C4, Canada. Source: Quto b, Sami S Ng, Cheng E Cancer-Chemother-Pharmacol. 2002 February; 49(2): 167-75 0344-5704

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Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a single-centre randomized four-arm study. Author(s): Institute for Oncology and Radiology of Serbia, Department of Medical Oncology, Pasterova 14, 11000 Belgrade, Yugoslavia. [email protected] Source: Jelic, S Babovic, N Kovcin, V Milicevic, N Milanovic, N Popov, I Radosavljevic, D Melanoma-Res. 2002 February; 12(1): 91-8 0960-8931

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: ·

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.thedacare.org/healthnotes/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDÒHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

The following is a specific Web list relating to melanoma; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation:

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·

Vitamins Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525, 10066,00.html

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Minerals Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Cisplatin.htm Selenium Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000233.html

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Food and Diet Omega-6 Fatty Acids Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsSupplements/O mega6FattyAcidscs.html Tea Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Food_Guide/Tea.htm

Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: Calcium: A mineral found in teeth, bones, and other body tissues. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH]

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Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Hypoxic: Having too little oxygen. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Phosphorous: Having to do with or containing the element phosphorus. [NIH]

Potassium: A metallic element that is important in body functions such as regulation of blood pressure and of water content in cells, transmission of nerve impulses, digestion, muscle contraction, and heart beat. [NIH] Radiology: The use of radiation (such as x-rays) or other imaging technologies (such as ultrasound and magnetic resonance imaging) to diagnose or treat disease. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its

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principal forms in tissues and cells are as FMN and FAD. [NIH] Selenium: An essential dietary mineral. [NIH] Thermoregulation: Heat regulation. [EU] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tomography: A series of detailed pictures of areas inside the body; the pictures are created by a computer linked to an x-ray machine. [NIH] Treosulfan: A substance that is being studied as a treatment for cancer. It belongs to the family of drugs called alkylating agents. [NIH]

Finding Medical Libraries 367

APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this appendix, we show you how to quickly find a medical library in your area.

Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, your local public library and medical libraries have Interlibrary Loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. NLM’s interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.166

166

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located):167 ·

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM

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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

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California: Kris Kelly Health Information Center (St. Joseph Health System), http://www.humboldt1.com/~kkhic/index.html

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California: Community Health Library of Los Gatos (Community Health Library of Los Gatos), http://www.healthlib.org/orgresources.html

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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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California: Health Library (Stanford University Medical Center), http://www-med.stanford.edu/healthlibrary/

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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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·

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: San José PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html

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California: University of California, Davis. Health Sciences Libraries

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html

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California: Washington Community Health Resource Library (Washington Community Health Resource Library), http://www.healthlibrary.org/

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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm

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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital), http://www.waterburyhospital.com/library/consumer.shtml

·

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm

·

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine), http://www.delamed.org/chls.html

·

Georgia: Family Resource Library (Medical College of Georgia), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

·

Georgia: Health Resource Center (Medical Center of Central Georgia), http://www.mccg.org/hrc/hrchome.asp

·

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library), http://hml.org/CHIS/

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·

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center), http://www.nicon.org/DeArmond/index.htm

·

Illinois: Health Learning Center of Northwestern Memorial Hospital (Northwestern Memorial Hospital, Health Learning Center), http://www.nmh.org/health_info/hlc.html

·

Illinois: Medical Library (OSF Saint Francis Medical Center), http://www.osfsaintfrancis.org/general/library/

·

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital), http://www.centralbap.com/education/community/library.htm

·

Kentucky: University of Kentucky - Health Information Library (University of Kentucky, Chandler Medical Center, Health Information Library), http://www.mc.uky.edu/PatientEd/

·

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation), http://www.ochsner.org/library/

·

Louisiana: Louisiana State University Health Sciences Center Medical Library-Shreveport, http://lib-sh.lsuhsc.edu/

·

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital), http://www.fchn.org/fmh/lib.htm

·

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center), http://www.cmmc.org/library/library.html

·

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare), http://www.emh.org/hll/hpl/guide.htm

·

Maine: Maine Medical Center Library (Maine Medical Center), http://www.mmc.org/library/

·

Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library

·

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center), http://www.smmc.org/services/service.php3?choice=10

·

Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html

·

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml

Finding Medical Libraries 371

·

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Md., Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

·

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

·

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://medlibwww.bu.edu/library/lib.html

·

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

·

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital), http://www.nebh.org/health_lib.asp

·

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital), http://www.southcoast.org/library/

·

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

·

Massachusetts: UMass HealthNet (University of Massachusetts Medical School), http://healthnet.umassmed.edu/

·

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

·

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

·

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

·

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41

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·

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

·

National: National Network of Libraries of Medicine (National Library of Medicine) - provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

·

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

·

Nevada: Health Science Library, West Charleston Library (Las Vegas Clark County Library District), http://www.lvccld.org/special_collections/medical/index.htm

·

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

·

New Jersey: Consumer Health Library (Rahway Hospital), http://www.rahwayhospital.com/library.htm

·

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center), http://www.englewoodhospital.com/links/index.htm

·

New Jersey: Meland Foundation (Englewood Hospital and Medical Center), http://www.geocities.com/ResearchTriangle/9360/

·

New York: Choices in Health Information (New York Public Library) NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

·

New York: Health Information Center (Upstate Medical University, State University of New York), http://www.upstate.edu/library/hic/

·

New York: Health Sciences Library (Long Island Jewish Medical Center), http://www.lij.edu/library/library.html

·

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

·

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

·

Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp

Finding Medical Libraries 373

·

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center), http://www.mcmc.net/phrc/

·

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center), http://www.hmc.psu.edu/commhealth/

·

Pennsylvania: Community Health Resource Library (Geisinger Medical Center), http://www.geisinger.edu/education/commlib.shtml

·

Pennsylvania: HealthInfo Library (Moses Taylor Hospital), http://www.mth.org/healthwellness.html

·

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System), http://www.hsls.pitt.edu/chi/hhrcinfo.html

·

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

·

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System), http://www.shscares.org/services/lrc/index.asp

·

Pennsylvania: Medical Library (UPMC Health System), http://www.upmc.edu/passavant/library.htm

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/

·

South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm

·

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

·

Texas: Matustik Family Resource Center (Cook Children’s Health Care System), http://www.cookchildrens.com/Matustik_Library.html

·

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

·

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/

Your Rights and Insurance 375

APPENDIX E. YOUR RIGHTS AND INSURANCE Overview Any patient with melanoma faces a series of issues related more to the healthcare industry than to the medical condition itself. This appendix covers two important topics in this regard: your rights and responsibilities as a patient, and how to get the most out of your medical insurance plan.

Your Rights as a Patient The President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has created the following summary of your rights as a patient.168 Information Disclosure Consumers have the right to receive accurate, easily understood information. Some consumers require assistance in making informed decisions about health plans, health professionals, and healthcare facilities. Such information includes: ·

Health plans. Covered benefits, cost-sharing, and procedures for resolving complaints, licensure, certification, and accreditation status, comparable measures of quality and consumer satisfaction, provider network composition, the procedures that govern access to specialists and emergency services, and care management information.

168Adapted

from Consumer Bill of Rights and Responsibilities: http://www.hcqualitycommission.gov/press/cbor.html#head1.

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·

Health professionals. Education, board certification, and recertification, years of practice, experience performing certain procedures, and comparable measures of quality and consumer satisfaction.

·

Healthcare facilities. Experience in performing certain procedures and services, accreditation status, comparable measures of quality, worker, and consumer satisfaction, and procedures for resolving complaints.

·

Consumer assistance programs. Programs must be carefully structured to promote consumer confidence and to work cooperatively with health plans, providers, payers, and regulators. Desirable characteristics of such programs are sponsorship that ensures accountability to the interests of consumers and stable, adequate funding.

Choice of Providers and Plans Consumers have the right to a choice of healthcare providers that is sufficient to ensure access to appropriate high-quality healthcare. To ensure such choice, the Commission recommends the following: ·

Provider network adequacy. All health plan networks should provide access to sufficient numbers and types of providers to assure that all covered services will be accessible without unreasonable delay -including access to emergency services 24 hours a day and 7 days a week. If a health plan has an insufficient number or type of providers to provide a covered benefit with the appropriate degree of specialization, the plan should ensure that the consumer obtains the benefit outside the network at no greater cost than if the benefit were obtained from participating providers.

·

Women’s health services. Women should be able to choose a qualified provider offered by a plan -- such as gynecologists, certified nurse midwives, and other qualified healthcare providers -- for the provision of covered care necessary to provide routine and preventative women’s healthcare services.

·

Access to specialists. Consumers with complex or serious medical conditions who require frequent specialty care should have direct access to a qualified specialist of their choice within a plan’s network of providers. Authorizations, when required, should be for an adequate number of direct access visits under an approved treatment plan.

·

Transitional care. Consumers who are undergoing a course of treatment for a chronic or disabling condition (or who are in the second or third trimester of a pregnancy) at the time they involuntarily change health

Your Rights and Insurance 377

plans or at a time when a provider is terminated by a plan for other than cause should be able to continue seeing their current specialty providers for up to 90 days (or through completion of postpartum care) to allow for transition of care. ·

Choice of health plans. Public and private group purchasers should, wherever feasible, offer consumers a choice of high-quality health insurance plans.

Access to Emergency Services Consumers have the right to access emergency healthcare services when and where the need arises. Health plans should provide payment when a consumer presents to an emergency department with acute symptoms of sufficient severity--including severe pain--such that a “prudent layperson” could reasonably expect the absence of medical attention to result in placing that consumer’s health in serious jeopardy, serious impairment to bodily functions, or serious dysfunction of any bodily organ or part.

Participation in Treatment Decisions Consumers have the right and responsibility to fully participate in all decisions related to their healthcare. Consumers who are unable to fully participate in treatment decisions have the right to be represented by parents, guardians, family members, or other conservators. Physicians and other health professionals should: ·

Provide patients with sufficient information and opportunity to decide among treatment options consistent with the informed consent process.

·

Discuss all treatment options with a patient in a culturally competent manner, including the option of no treatment at all.

·

Ensure that persons with disabilities have effective communications with members of the health system in making such decisions.

·

Discuss all current treatments a consumer may be undergoing.

·

Discuss all risks, nontreatment.

·

Give patients the opportunity to refuse treatment and to express preferences about future treatment decisions.

benefits,

and

consequences

to

treatment

or

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·

Discuss the use of advance directives -- both living wills and durable powers of attorney for healthcare -- with patients and their designated family members.

·

Abide by the decisions made by their patients and/or their designated representatives consistent with the informed consent process.

Health plans, health providers, and healthcare facilities should: ·

Disclose to consumers factors -- such as methods of compensation, ownership of or interest in healthcare facilities, or matters of conscience -that could influence advice or treatment decisions.

·

Assure that provider contracts do not contain any so-called “gag clauses” or other contractual mechanisms that restrict healthcare providers’ ability to communicate with and advise patients about medically necessary treatment options.

·

Be prohibited from penalizing or seeking retribution against healthcare professionals or other health workers for advocating on behalf of their patients.

Respect and Nondiscrimination Consumers have the right to considerate, respectful care from all members of the healthcare industry at all times and under all circumstances. An environment of mutual respect is essential to maintain a quality healthcare system. To assure that right, the Commission recommends the following: ·

Consumers must not be discriminated against in the delivery of healthcare services consistent with the benefits covered in their policy, or as required by law, based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment.

·

Consumers eligible for coverage under the terms and conditions of a health plan or program, or as required by law, must not be discriminated against in marketing and enrollment practices based on race, ethnicity, national origin, religion, sex, age, mental or physical disability, sexual orientation, genetic information, or source of payment. Confidentiality of Health Information

Consumers have the right to communicate with healthcare providers in confidence and to have the confidentiality of their individually identifiable

Your Rights and Insurance 379

healthcare information protected. Consumers also have the right to review and copy their own medical records and request amendments to their records. Complaints and Appeals Consumers have the right to a fair and efficient process for resolving differences with their health plans, healthcare providers, and the institutions that serve them, including a rigorous system of internal review and an independent system of external review. A free copy of the Patient’s Bill of Rights is available from the American Hospital Association.169

Patient Responsibilities Treatment is a two-way street between you and your healthcare providers. To underscore the importance of finance in modern healthcare as well as your responsibility for the financial aspects of your care, the President’s Advisory Commission on Consumer Protection and Quality in the Healthcare Industry has proposed that patients understand the following “Consumer Responsibilities.”170 In a healthcare system that protects consumers’ rights, it is reasonable to expect and encourage consumers to assume certain responsibilities. Greater individual involvement by the consumer in his or her care increases the likelihood of achieving the best outcome and helps support a quality-oriented, cost-conscious environment. Such responsibilities include: ·

Take responsibility for maximizing healthy habits such as exercising, not smoking, and eating a healthy diet.

·

Work collaboratively with healthcare providers in developing and carrying out agreed-upon treatment plans.

·

Disclose relevant information and clearly communicate wants and needs.

·

Use your health insurance plan’s internal complaint and appeal processes to address your concerns.

·

Avoid knowingly spreading disease.

To order your free copy of the Patient’s Bill of Rights, telephone 312-422-3000 or visit the American Hospital Association’s Web site: http://www.aha.org. Click on “Resource Center,” go to “Search” at bottom of page, and then type in “Patient’s Bill of Rights.” The Patient’s Bill of Rights is also available from Fax on Demand, at 312-422-2020, document number 471124. 170 Adapted from http://www.hcqualitycommission.gov/press/cbor.html#head1. 169

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·

Recognize the reality of risks, the limits of the medical science, and the human fallibility of the healthcare professional.

·

Be aware of a healthcare provider’s obligation to be reasonably efficient and equitable in providing care to other patients and the community.

·

Become knowledgeable about your health plan’s coverage and options (when available) including all covered benefits, limitations, and exclusions, rules regarding use of network providers, coverage and referral rules, appropriate processes to secure additional information, and the process to appeal coverage decisions.

·

Show respect for other patients and health workers.

·

Make a good-faith effort to meet financial obligations.

·

Abide by administrative and operational procedures of health plans, healthcare providers, and Government health benefit programs.

Choosing an Insurance Plan There are a number of official government agencies that help consumers understand their healthcare insurance choices.171 The U.S. Department of Labor, in particular, recommends ten ways to make your health benefits choices work best for you.172 1. Your options are important. There are many different types of health benefit plans. Find out which one your employer offers, then check out the plan, or plans, offered. Your employer’s human resource office, the health plan administrator, or your union can provide information to help you match your needs and preferences with the available plans. The more information you have, the better your healthcare decisions will be. 2. Reviewing the benefits available. Do the plans offered cover preventive care, well-baby care, vision or dental care? Are there deductibles? Answers to these questions can help determine the out-of-pocket expenses you may face. Matching your needs and those of your family members will result in the best possible benefits. Cheapest may not always be best. Your goal is high quality health benefits.

More information about quality across programs is provided at the following AHRQ Web site: http://www.ahrq.gov/consumer/qntascii/qnthplan.htm. 172 Adapted from the Department of Labor: http://www.dol.gov/dol/pwba/public/pubs/health/top10-text.html. 171

Your Rights and Insurance 381

3. Look for quality. The quality of healthcare services varies, but quality can be measured. You should consider the quality of healthcare in deciding among the healthcare plans or options available to you. Not all health plans, doctors, hospitals and other providers give the highest quality care. Fortunately, there is quality information you can use right now to help you compare your healthcare choices. Find out how you can measure quality. Consult the U.S. Department of Health and Human Services publication “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer. 4. Your plan’s summary plan description (SPD) provides a wealth of information. Your health plan administrator can provide you with a copy of your plan’s SPD. It outlines your benefits and your legal rights under the Employee Retirement Income Security Act (ERISA), the federal law that protects your health benefits. It should contain information about the coverage of dependents, what services will require a co-pay, and the circumstances under which your employer can change or terminate a health benefits plan. Save the SPD and all other health plan brochures and documents, along with memos or correspondence from your employer relating to health benefits. 5. Assess your benefit coverage as your family status changes. Marriage, divorce, childbirth or adoption, and the death of a spouse are all life events that may signal a need to change your health benefits. You, your spouse and dependent children may be eligible for a special enrollment period under provisions of the Health Insurance Portability and Accountability Act (HIPAA). Even without life-changing events, the information provided by your employer should tell you how you can change benefits or switch plans, if more than one plan is offered. If your spouse’s employer also offers a health benefits package, consider coordinating both plans for maximum coverage. 6. Changing jobs and other life events can affect your health benefits. Under the Consolidated Omnibus Budget Reconciliation Act (COBRA), you, your covered spouse, and your dependent children may be eligible to purchase extended health coverage under your employer’s plan if you lose your job, change employers, get divorced, or upon occurrence of certain other events. Coverage can range from 18 to 36 months depending on your situation. COBRA applies to most employers with 20 or more workers and requires your plan to notify you of your rights. Most plans require eligible individuals to make their COBRA election within 60 days of the plan’s notice. Be sure to follow up with your plan sponsor if you don’t receive notice, and make sure you respond within the allotted time.

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7. HIPAA can also help if you are changing jobs, particularly if you have a medical condition. HIPAA generally limits pre-existing condition exclusions to a maximum of 12 months (18 months for late enrollees). HIPAA also requires this maximum period to be reduced by the length of time you had prior “creditable coverage.” You should receive a certificate documenting your prior creditable coverage from your old plan when coverage ends. 8. Plan for retirement. Before you retire, find out what health benefits, if any, extend to you and your spouse during your retirement years. Consult with your employer’s human resources office, your union, the plan administrator, and check your SPD. Make sure there is no conflicting information among these sources about the benefits you will receive or the circumstances under which they can change or be eliminated. With this information in hand, you can make other important choices, like finding out if you are eligible for Medicare and Medigap insurance coverage. 9. Know how to file an appeal if your health benefits claim is denied. Understand how your plan handles grievances and where to make appeals of the plan’s decisions. Keep records and copies of correspondence. Check your health benefits package and your SPD to determine who is responsible for handling problems with benefit claims. Contact PWBA for customer service assistance if you are unable to obtain a response to your complaint. 10. You can take steps to improve the quality of the healthcare and the health benefits you receive. Look for and use things like Quality Reports and Accreditation Reports whenever you can. Quality reports may contain consumer ratings -- how satisfied consumers are with the doctors in their plan, for instance-- and clinical performance measures -- how well a healthcare organization prevents and treats illness. Accreditation reports provide information on how accredited organizations meet national standards, and often include clinical performance measures. Look for these quality measures whenever possible. Consult “Your Guide to Choosing Quality Health Care” on the Internet at www.ahcpr.gov/consumer.

Medicare and Medicaid Illness strikes both rich and poor families. For low-income families, Medicaid is available to defer the costs of treatment. The Health Care Financing Administration (HCFA) administers Medicare, the nation’s largest health insurance program, which covers 39 million Americans. In the following pages, you will learn the basics about Medicare insurance as well as useful

Your Rights and Insurance 383

contact information on how to find more in-depth information about Medicaid.173

Who is Eligible for Medicare? Generally, you are eligible for Medicare if you or your spouse worked for at least 10 years in Medicare-covered employment and you are 65 years old and a citizen or permanent resident of the United States. You might also qualify for coverage if you are under age 65 but have a disability or EndStage Renal disease (permanent kidney failure requiring dialysis or transplant). Here are some simple guidelines: You can get Part A at age 65 without having to pay premiums if: ·

You are already receiving retirement benefits from Social Security or the Railroad Retirement Board.

·

You are eligible to receive Social Security or Railroad benefits but have not yet filed for them.

·

You or your spouse had Medicare-covered government employment.

If you are under 65, you can get Part A without having to pay premiums if: ·

You have received Social Security or Railroad Retirement Board disability benefit for 24 months.

·

You are a kidney dialysis or kidney transplant patient.

Medicare has two parts: ·

Part A (Hospital Insurance). Most people do not have to pay for Part A.

·

Part B (Medical Insurance). Most people pay monthly for Part B. Part A (Hospital Insurance)

Helps Pay For: Inpatient hospital care, care in critical access hospitals (small facilities that give limited outpatient and inpatient services to people in rural areas) and skilled nursing facilities, hospice care, and some home healthcare.

This section has been adapted from the Official U.S. Site for Medicare Information: http://www.medicare.gov/Basics/Overview.asp.

173

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Cost: Most people get Part A automatically when they turn age 65. You do not have to pay a monthly payment called a premium for Part A because you or a spouse paid Medicare taxes while you were working. If you (or your spouse) did not pay Medicare taxes while you were working and you are age 65 or older, you still may be able to buy Part A. If you are not sure you have Part A, look on your red, white, and blue Medicare card. It will show “Hospital Part A” on the lower left corner of the card. You can also call the Social Security Administration toll free at 1-800-772-1213 or call your local Social Security office for more information about buying Part A. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Fiscal Intermediary about Part A bills and services. The phone number for the Fiscal Intermediary office in your area can be obtained from the following Web site: http://www.medicare.gov/Contacts/home.asp. Part B (Medical Insurance) Helps Pay For: Doctors, services, outpatient hospital care, and some other medical services that Part A does not cover, such as the services of physical and occupational therapists, and some home healthcare. Part B helps pay for covered services and supplies when they are medically necessary. Cost: As of 2001, you pay the Medicare Part B premium of $50.00 per month. In some cases this amount may be higher if you did not choose Part B when you first became eligible at age 65. The cost of Part B may go up 10% for each 12-month period that you were eligible for Part B but declined coverage, except in special cases. You will have to pay the extra 10% cost for the rest of your life. Enrolling in Part B is your choice. You can sign up for Part B anytime during a 7-month period that begins 3 months before you turn 65. Visit your local Social Security office, or call the Social Security Administration at 1-800-7721213 to sign up. If you choose to enroll in Part B, the premium is usually taken out of your monthly Social Security, Railroad Retirement, or Civil Service Retirement payment. If you do not receive any of the above payments, Medicare sends you a bill for your part B premium every 3 months. You should receive your Medicare premium bill in the mail by the 10th of the month. If you do not, call the Social Security Administration at 1800-772-1213, or your local Social Security office. If you get benefits from the Railroad Retirement Board, call your local RRB office or 1-800-808-0772. For more information, call your Medicare carrier about bills and services. The

Your Rights and Insurance 385

phone number for the Medicare carrier in your area can be found at the following Web site: http://www.medicare.gov/Contacts/home.asp. You may have choices in how you get your healthcare including the Original Medicare Plan, Medicare Managed Care Plans (like HMOs), and Medicare Private Fee-for-Service Plans.

Medicaid Medicaid is a joint federal and state program that helps pay medical costs for some people with low incomes and limited resources. Medicaid programs vary from state to state. People on Medicaid may also get coverage for nursing home care and outpatient prescription drugs which are not covered by Medicare. You can find more information about Medicaid on the HCFA.gov Web site at http://www.hcfa.gov/medicaid/medicaid.htm. States also have programs that pay some or all of Medicare’s premiums and may also pay Medicare deductibles and coinsurance for certain people who have Medicare and a low income. To qualify, you must have: ·

Part A (Hospital Insurance),

·

Assets, such as bank accounts, stocks, and bonds that are not more than $4,000 for a single person, or $6,000 for a couple, and

·

A monthly income that is below certain limits.

For more information on these programs, look at the Medicare Savings Programs brochure, http://www.medicare.gov/Library/PDFNavigation/PDFInterim.asp?Langua ge=English&Type=Pub&PubID=10126. There are also Prescription Drug Assistance Programs available. Find information on these programs which offer discounts or free medications to individuals in need at http://www.medicare.gov/Prescription/Home.asp.

Financial Assistance for Cancer Care174 Cancer imposes heavy economic burdens on both patients and their families. For many people, a portion of medical expenses is paid by their health insurance plan. For individuals who do not have health insurance or who need financial assistance to cover health care costs, resources are available,

174

Adapted from the NCI: http://cis.nci.nih.gov/fact/8_3.htm.

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including government-sponsored programs and services supported by voluntary organizations. Cancer patients and their families should discuss any concerns they may have about health care costs with their physician, medical social worker, or the business office of their hospital or clinic. The organizations and resources listed below may offer financial assistance. Organizations that provide publications in Spanish or have Spanishspeaking staff have been identified. ·

The American Cancer Society (ACS) office can provide the telephone number of the local ACS office serving your area. The local ACS office may offer reimbursement for expenses related to cancer treatment including transportation, medicine, and medical supplies. The ACS also offers programs that help cancer patients, family members, and friends cope with the emotional challenges they face. Some publications are available in Spanish. Spanish-speaking staff are available. Telephone: 1– 800–ACS–2345 (1–800–227–2345). Web site: http://www.cancer.org

·

The AVONCares Program for Medically Underserved Women provides financial assistance and relevant education and support to low income, under- and uninsured, underserved women throughout the country in need of diagnostic and/or related services (transportation, child care, and social support) for the treatment of breast, cervical, and ovarian cancers. Telephone: 1–800–813–HOPE (1–800–813–4673). Web site: http://www.cancercare.org.

Community voluntary agencies and service organizations such as the Salvation Army, Lutheran Social Services, Jewish Social Services, Catholic Charities, and the Lions Club may offer help. These organizations are listed in your local phone directory. Some churches and synagogues may provide financial help or services to their members. Fundraising is another mechanism to consider. Some patients find that friends, family, and community members are willing to contribute financially if they are aware of a difficult situation. Contact your local library for information about how to organize fundraising efforts. General assistance programs provide food, housing, prescription drugs, and other medical expenses for those who are not eligible for other programs. Funds are often limited. Information can be obtained by contacting your state or local Department of Social Services; this number is found in the local telephone directory.

Your Rights and Insurance 387

Hill-Burton is a program through which hospitals receive construction funds from the Federal Government. Hospitals that receive Hill-Burton funds are required by law to provide some services to people who cannot afford to pay for their hospitalization. Information about which facilities are part of this program is available by calling the toll-free number or visiting the Web site shown below. A brochure about the program is available in Spanish. Telephone: 1–800–638–0742. Web site: http://www.hrsa.gov/osp/dfcr/obtain/consfaq.htm.

Income Tax Deductions Medical costs that are not covered by insurance policies sometimes can be deducted from annual income before taxes. Examples of tax deductible expenses might include mileage for trips to and from medical appointments, out-of-pocket costs for treatment, prescription drugs or equipment, and the cost of meals during lengthy medical visits. The local Internal Revenue Service office, tax consultants, or certified public accountants can determine medical costs that are tax deductible. These telephone numbers are available in the local telephone directory. Web site: http://www.irs.ustreas.gov.

The Patient Advocate Foundation The Patient Advocate Foundation (PAF) is a national nonprofit organization that provides education, legal counseling, and referrals to cancer patients and survivors concerning managed care, insurance, financial issues, job discrimination, and debt crisis matters. Telephone: 1–800–532–5274. Web site: http://www.patientadvocate.org. Patient Assistance Programs are offered by some pharmaceutical manufacturers to help pay for medications. To learn whether a specific drug might be available at reduced cost through such a program, talk with a physician or a medical social worker.

Transportation There are nonprofit organizations that arrange free or reduced cost air transportation for cancer patients going to or from cancer treatment centers. Financial need is not always a requirement. To find out about these programs, talk with a medical social worker. Ground transportation services

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may be offered or mileage reimbursed through the local ACS or your state or local Department of Social Services.

Veterans Benefits Eligible veterans and their dependents may receive cancer treatment at a Veterans Administration Medical Center. Treatment for service-connected conditions is provided, and treatment for other conditions may be available based on the veteran’s financial need. Some publications are available in Spanish. Spanish-speaking staff are available in some offices. Telephone: 1– 877–222–VETS. Web site: http://www.va.gov/vbs/health.

NORDs Medication Assistance Programs Finally, the National Organization for Rare Disorders, Inc. (NORD) administers medication programs sponsored by humanitarian-minded pharmaceutical and biotechnology companies to help uninsured or underinsured individuals secure life-saving or life-sustaining drugs.175 NORD programs ensure that certain vital drugs are available “to those individuals whose income is too high to qualify for Medicaid but too low to pay for their prescribed medications.” The program has standards for fairness, equity, and unbiased eligibility. It currently covers some 14 programs for nine pharmaceutical companies. NORD also offers early access programs for investigational new drugs (IND) under the approved “Treatment INDs” programs of the Food and Drug Administration (FDA). In these programs, a limited number of individuals can receive investigational drugs that have yet to be approved by the FDA. These programs are generally designed for rare diseases or disorders. For more information, visit www.rarediseases.org.

Adapted from NORD: http://www.rarediseases.org/cgibin/nord/progserv#patient?id=rPIzL9oD&mv_pc=30.

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Your Rights and Insurance 389

Additional Resources In addition to the references already listed in this chapter, you may need more information on health insurance, hospitals, or the healthcare system in general. The NIH has set up an excellent guidance Web site that addresses these and other issues. Topics include:176 ·

Health Insurance: http://www.nlm.nih.gov/medlineplus/healthinsurance.html

·

Health Statistics: http://www.nlm.nih.gov/medlineplus/healthstatistics.html

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HMO and Managed Care: http://www.nlm.nih.gov/medlineplus/managedcare.html

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Hospice Care: http://www.nlm.nih.gov/medlineplus/hospicecare.html

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Medicaid: http://www.nlm.nih.gov/medlineplus/medicaid.html

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Medicare: http://www.nlm.nih.gov/medlineplus/medicare.html

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Nursing Homes and Long-term Care: http://www.nlm.nih.gov/medlineplus/nursinghomes.html

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Patient’s Rights, Confidentiality, Informed Consent, Ombudsman Programs, Privacy and Patient Issues: http://www.nlm.nih.gov/medlineplus/patientissues.html

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Veteran’s Health, Persian Gulf War, Gulf War Syndrome, Agent Orange: http://www.nlm.nih.gov/medlineplus/veteranshealth.html

You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

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Vocabulary Builder Conjunctiva: A membrane that lines the inner surface of the eyelid and also covers the front part of the eye. Conjunctivitis is inflammation of the conjunctiva. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH]

Online Glossaries 391

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. The National Library of Medicine has compiled the following list of online dictionaries: ·

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

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On-line Medical Dictionary (CancerWEB): http://www.graylab.ac.uk/omd/

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

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Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html

Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to melanoma and keep them on file. The NIH, in particular, suggests that patients with melanoma visit the following Web sites in the ADAM Medical Encyclopedia:

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·

Basic Guidelines for Melanoma Malignant melanoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001442.htm Melanoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm Melanoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001442.htm Melanoma of the eye Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001022.htm

·

Signs & Symptoms for Melanoma Blistering Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Eyes, bulging Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003033.htm Hyperpigmentation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003242.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Macule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003229.htm

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Painful eye Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003032.htm Papule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003233.htm Poor vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Skin lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Sunburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003227.htm ·

Diagnostics and Tests for Melanoma Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Cranial CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003786.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Lymph node biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003933.htm

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MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm MRI of the head Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003791.htm Punch biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Skin biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Skin lesion biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm ·

Surgery and Procedures for Melanoma Skin graft Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002982.htm

·

Background Topics for Melanoma Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm

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Cancer - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002166.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Choroid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002318.htm Conjunctiva Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002326.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Iris Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002386.htm Macule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003229.htm Melanin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002256.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm

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Retina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002291.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

·

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

·

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

Glossary 397

MELANOMA GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Abdomen: The part of the body that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Accommodation: distances. [EU]

Adjustment, especially that of the eye for various

Acetaminophen: A drug that reduces pain and fever (but not inflammation). [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Aetiology: Study of the causes of disease. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Anesthesia: Loss of feeling or awareness. Local anesthetics cause loss of feeling in a part of the body. General anesthetics put the person to sleep. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the

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release of chemicals by the tumor. [NIH] Anthrax: An infectious bacterial zoonotic disease usually acquired by ingestion of Bacillus anthracis or its spores from infected pastures by herbivores or indirectly from infected carcasses by carnivores. It is transmitted to humans usually by contact with infected animals or their discharges (agricultural a.) or with contaminated animal products (industrial a.). Anthrax is classified by primary routes of inoculation as : cutaneous, gastrointestinal, and inhalational. Called also charbon, milzbrand and splenic fever. [EU] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antigens: Substances that cause the immune system to make a specific immune response. [NIH] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastons: Substances isolated from normal human blood and urine being tested as a type of treatment for some tumors and AIDS. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: A normal series of events in a cell that leads to its death. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Ascites: Abnormal buildup of fluid in the abdomen. [NIH] Aspiration: Removal of fluid from a lump, often a cyst, with a needle and a syringe. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-

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shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autopsy: Postmortem examination of the body. [NIH] Bacillus: A genus of bacteria of the family Bacillaceae, including large aerobic or facultatively anaerobic, spore-forming, rod-shaped cells, the great majority of which are gram-positive and motile. The genus is separated into 48 species, of which three are pathogenic, or potentially pathogenic, and the remainder are saprophytic soil forms. Many organisms historically called Bacillus are now classified in other genera. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Bevacizumab: A monoclonal antibody that may prevent the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: The removal of cells or tissues for examination under a microscope. When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When an entire tumor or lesion is removed, the procedure is called an excisional biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle biopsy or fineneedle aspiration. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics. [NIH] Calcium: A mineral found in teeth, bones, and other body tissues. [NIH] Camptothecin: An anticancer drug that belongs to the family of drugs called topoisomerase inhibitors. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as

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semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU]

Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Carboplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH] Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Charities: Social welfare organizations with programs designed to assist individuals in times of need. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorofluorocarbons: A series of hydrocarbons containing both chlorine

Glossary 401

and fluorine. These have been used as refrigerants, blowing agents, cleaning fluids, solvents, and as fire extinguishing agents. They have been shown to cause stratospheric ozone depletion and have been banned for many uses. [NIH]

Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chondrosarcoma: A type of cancer that forms in cartilage. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Cisplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] CNS: Central nervous system. The brain and spinal cord. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: A membrane that lines the inner surface of the eyelid and also covers the front part of the eye. Conjunctivitis is inflammation of the conjunctiva. [NIH] Constitutional: 1. affecting the whole constitution of the body; not local. 2. pertaining to the constitution. [EU] Contraceptive: conception. [EU]

An agent that diminishes the likelihood of or prevents

Corpus: The body of the uterus. [NIH] Corynebacterium: A genus of asporogenous bacteria that is widely distributed in nature. Its organisms appear as straight to slightly curved rods and are known to be human and animal parasites and pathogens. [NIH] Cryosurgery: Treatment performed with an instrument that freezes and destroys abnormal tissues. This procedure is a form of cryotherapy. [NIH] Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH]

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Cyclophosphamide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Cysteinyldopa: Found in large amounts in the plasma and urine of patients with malignant melanoma. It is therefore used in the diagnosis of melanoma and for the detection of postoperative metastases. Cysteinyldopa is believed to be formed by the rapid enzymatic hydrolysis of 5-S-glutathionedopa found in melanin-producing cells. [NIH] Cytokines: A class of substances that are produced by cells of the immune system and can affect the immune response. Cytokines can also be produced in the laboratory by recombinant DNA technology and given to people to affect immune responses. [NIH] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Dacarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dendritic: 1. branched like a tree. 2. pertaining to or possessing dendrites. [EU]

Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Dexamethasone: A synthetic steroid (similar to steroid hormones produced naturally in the adrenal gland). Dexamethasone is used to treat leukemia and lymphoma and may be used to treat some of the problems caused by other cancers and their treatment. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Doxorubicin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics. It is an anthracycline. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH]

Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents, characterized in the acute stage by erythema, edema associated with a serous exudate between the cells of the epidermis (spongiosis) and an inflammatory infiltrate in the dermis, oozing and vesiculation, and crusting and scaling; and in the more chronic stages by

Glossary 403

lichenification or thickening or both, signs of excoriations, and hyperpigmentation or hypopigmentation or both. Atopic dermatitis is the most common type of dermatitis. Called also eczematous dermatitis. [EU] Electrodesiccation: The drying of tissue by a high-frequency electric current applied with a needle-shaped electrode. [NIH] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other health-related event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: The upper or outer layer of the two main layers of tissue that make up the skin. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Etoposide: An anticancer drug that is a podophyllotoxin derivative and belongs to the family of drugs called mitotic inhibitors. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU]

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Fenretinide: A drug being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Flt3L: A drug that increases the number of immune cells and may stimulate the immune system to kill cancer cells. [NIH] Fluorouracil: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Folliculitis: Inflammation of a follicle or follicles; used ordinarily in reference to hair follicles, but sometimes in relation to follicles of other kinds. [EU]

Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Ginseng: An herb with a root that has been used in some cultures to treat certain medical problems. It may have anticancer effects. [NIH] Glioblastoma: A general term that refers to malignant astrocytoma, a type of brain tumor. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH]

Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious

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agents. [NIH] Groin: The area where the thigh meets the abdomen. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Hematogenous: bloodstream. [NIH]

Originating in the blood or spread through the

Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hyperplasia: An abnormal increase in the number of cells in an organ or tissue. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Immunity: The condition of being immune; the protection against infectious disease conferred either by the immune response generated by immunization or previous infection or by other nonimmunologic factors (innate i.). [EU] Immunization: The induction of immunity. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH]

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Immunosuppression: Suppression of the body's immune system and its ability to fight infections or disease. Immunosuppression may be deliberately induced with drugs, as in preparation for bone marrow or other organ transplantation to prevent rejection of the donor tissue. It may also result from certain diseases such as AIDS or lymphoma or from anticancer drugs. [NIH] Immunosuppressive: responses. [NIH]

Describes the ability to lower immune system

Immunotherapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also called biological therapy or biological response modifier (BRM) therapy. [NIH] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A response of redness, swelling, pain, and a feeling of heat in certain areas which is meant to protect tissues affected by injury or disease. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inoperable: Not suitable to be operated upon. [EU] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation

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of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intravenous: IV. Into a vein. [NIH] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

Ipsilateral: Having to do with the same side of the body. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Keloid: A thick, irregular scar caused by excessive tissue growth at the site of an incision or wound. [NIH] Keratoacanthoma: A benign (noncancerous), rapidly growing skin tumor that usually occurs on sun-exposed areas of the skin and that can go away without treatment. [NIH] Keratosis: Any horny growth such as a wart or callus. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lectins: Protein or glycoprotein substances, usually of plant origin, that bind to sugar moieties in cell walls or membranes and thereby change the physiology of the membrane to cause agglutination, mitosis, or other biochemical changes in the cell. [NIH] Lethal: Deadly, fatal. [EU] Leukapheresis: Removal of the blood to collect specific blood cells; the remaining blood is returned to the body. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Lipid: Fat. [NIH] Lipoxygenase:

An enzyme of the oxidoreductase class that catalyzes

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reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5-lipoxygenase, arachidonate 12lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Lomustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. Also called lymph node dissection. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoma: Cancer that arises in cells of the lymphatic system. [NIH] Lymphoscintigraphy: A method used to identify the sentinel node (the first draining lymph node near a tumor). A radioactive substance that can be taken up by lymph nodes is injected at the site of the tumor, and a doctor follows the movement of this substance on a computer screen. Once the lymph nodes that have taken up the substance are identified, they can be removed and examined to see if they contain tumor cells. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammography: The use of x-rays to create a picture of the breast. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU]

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Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Cells in the skin that produce and contain the pigment called melanin. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanosis: A disorder caused by a disturbance in melanin pigmentation; melanism. [EU] Melphalan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolite: process. [EU]

Any substance produced by metabolism or by a metabolic

Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methotrexate: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH]

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Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monocyte: A type of white blood cell. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mycobacterium: An organism of the genus Mycobacterium. [EU] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Necrosis: Refers to the death of living tissues. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and

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nucleic acids and found in all living cells. [NIH] Nitrosoureas: A group of anticancer drugs that can cross the blood-brain barrier. Carmustine and lomustine are nitrosoureas. [NIH] Nonmetastatic: Cancer that has not spread from the primary (original) site to other sites in the body. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Oligopeptides: Peptides composed of between two and twelve amino acids. [NIH]

Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Paclitaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH] Palliative: 1. affording relief, but not cure. 2. an alleviating medicine. [EU] Pancreas: A glandular organ located in the abdomen. It makes pancreatic juices, which contain enzymes that aid in digestion, and it produces several hormones, including insulin. The pancreas is surrounded by the stomach, intestines, and other organs. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pap test: The collection of cells from the cervix for examination under a microscope. It is used to detect changes that may be cancer or may lead to cancer, and can show noncancerous conditions, such as infection or

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inflammation. Also called a Pap smear. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] Particle: A tiny mass of material. [EU] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perineal: Pertaining to the perineum. [EU] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetics: The activity of drugs in the body over a period of time, including the processes by which drugs are absorbed, distributed in the body, localized in the tissues, and excreted. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH]

Pityriasis: A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. [EU] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH]

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Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: A metal that is an important component of some anticancer drugs, such as cisplatin and carboplatin. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyvalent: Having more than one valence. [EU] Potassium: A metallic element that is important in body functions such as regulation of blood pressure and of water content in cells, transmission of nerve impulses, digestion, muscle contraction, and heart beat. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH]

Proportional: Being in proportion: corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Pruritus: 1. itching; an unpleasant cutaneous sensation that provokes the desire to rub or scratch the skin to obtain relief. 2. any of various conditions

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marked by itching, the specific site or type being indicated by a modifying term. [EU] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A chronic disease of the skin marked by red patches covered with white scales. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrazoloacridine: An anticancer drug that belongs to the family of drugs called acridines. [NIH] Radiodermatitis: A cutaneous inflammatory reaction occurring as a result of exposure to ionizing radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH] Radiology: The use of radiation (such as x-rays) or other imaging technologies (such as ultrasound and magnetic resonance imaging) to diagnose or treat disease. [NIH] Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the diagnosis and treatment of cancer and in pain management of bone metastases. Also called radioactive drugs. [NIH] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Radium: Radium. A radioactive element of the alkaline earth series of metals. It has the atomic symbol Ra, atomic number 88, and atomic weight 226. Radium is the product of the disintegration of uranium and is present in pitchblende and all ores containing uranium. It is used clinically as a source of beta and gamma-rays in radiotherapy, particularly brachytherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH]

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Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]

Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Rheumatoid: Resembling rheumatism. [EU] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH]

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Sarcoma: A cancer of the bone, cartilage, fat, muscle, blood vessels or other connective or supportive tissue. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Scabies: A contagious dermatitis of humans and various wild and domestic animals caused by the itch mite, Sarcoptes scabiei, transmitted by close contact, and characterized by a papular eruption over tiny, raised sinuous burrows (cuniculi) produced by digging into the upper layer of the epidermis by the egg-laying female mite, which is accompanied by intense pruritus and sometimes associated with eczema from scratching and secondary bacterial infection. Called also the itch and seven-year itch. [EU] Schwannoma: A tumor of the peripheral nervous system that begins in the nerve sheath (protective covering). It is almost always benign, but rare malignant schwannomas have been reported. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. the process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. any substance produced by secretion. [EU] Selenium: An essential dietary mineral. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Somatic: 1. pertaining to or characteristic of the soma or body. 2. pertaining to the body wall in contrast to the viscera. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] SPF: Sun protection factor, scale for rating the level of sunburn protection in sunscreen products. The higher the SPF, the more sunburn protection it provides. Sunscreens with an SPF value of 2 through 11 provide minimal

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protection against sunburns. Sunscreens with an SPF of 12 through 29 provide moderate protection, which is adequate for most people. Those with an SPF of 30 or higher provide high protection against sunburn and are sometimes recommended for people who are highly sensitive to the sun. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spotting: A slight discharge of blood via the vagina, especially as a sideeffect of oral contraceptives. [EU] Squamous: Scaly, or platelike. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH] Stimulant: 1. producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. an agent or remedy that produces stimulation. [EU] Stomach: An organ that is part of the digestive system. It helps in the digestion of food by mixing it with digestive juices and churning it into a thin liquid. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] SU5416: An anticancer drug that belongs to the family of drugs called angiogenesis inhibitors. [NIH] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Substrate: A substance upon which an enzyme acts. [EU] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Sunscreen: A substance that helps protect the skin from the sun's harmful rays. Sunscreens reflect, absorb, and scatter both UVA and UVB radiation. Using lotions, creams, or gels that contain sunscreens can help protect the skin from premature aging and damage that may lead to skin cancer. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Systemic: Affecting the entire body. [NIH]

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Tamoxifen: An anticancer drug that belongs to the family of drugs called antiestrogens. Tamoxifen blocks the effects of the hormone estrogen in the body. It is used to prevent or delay the return of breast cancer or to control its spread. [NIH] Taxanes: Anticancer drugs that inhibit cancer cell growth by stopping cell division. Also called antimitotic or antimicrotubule agents or mitotic inhibitors. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetracycline: An antibiotic drug used to treat infection. [NIH] Thalidomide: A drug that belongs to the family of drugs called angiogenesis inhibitors. It prevents the growth of new blood vessels into a solid tumor. [NIH] Thermoregulation: Heat regulation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tolerance: 1. the ability to endure unusually large doses of a drug or toxin. 2. acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU]

Tomography: A series of detailed pictures of areas inside the body; the pictures are created by a computer linked to an x-ray machine. [NIH] Topical: On the surface of the body. [NIH]

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Transplantation: person. [NIH]

The replacement of an organ with one from another

Treosulfan: A substance that is being studied as a treatment for cancer. It belongs to the family of drugs called alkylating agents. [NIH] Tretinoin: A drug that belongs to the family of drugs called retinoids. It is used in the treatment of acne and is being studied in cancer prevention. [NIH] Trustees: Board members of an institution or organization who are entrusted with the administering of funds and the directing of policy. [NIH] Tumour: 1. swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. a new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulceration: 1. the formation or development of an ulcer. 2. an ulcer. [EU] Unresectable: Unable to be surgically removed. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Treatment with a vaccine. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and sometimes systemic reactions associated with vaccination with smallpox vaccine. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Veins: The vessels carrying blood toward the heart. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH]

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Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscum: A genus of Old World parasitic plants of the Loranthaceae. Viscum album and Phorandendron flavescens were formerly used as emmenagogues, cardiac stimulants, and vasodilators. The plants contain toxins, lectins, tyramine, phenethylamines, and other useful or dangerous compounds. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH]

Xenograft: The cells of one species transplanted to another species. [NIH]

General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

The Cancer Dictionary by Roberta Altman, Michael J., Md Sarg; Paperback - 368 pages, 2nd Revised edition (November 1999), Checkmark Books; ISBN: 0816039542; http://www.amazon.com/exec/obidos/ASIN/0816039542/icongroupinterna

·

Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna

·

Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna

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A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna

Glossary 421

·

Dorland’s Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna

·

Dorland’s Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna

·

Dorland’s Pocket Medical Dictionary (Dorland’s Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618

·

Melloni’s Illustrated Medical Dictionary (Melloni’s Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna

·

Stedman’s Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna

·

Stedman’s Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna

·

Stedman’s Oncology Words by Beverly J. Wolpert (Editor), Stedmans; Paperback - 502 pages, 3rd edition (June 15, 2000), Lippincott, Williams & Wilkins; ISBN: 0781726549; http://www.amazon.com/exec/obidos/ASIN/0781726549/icongroupinterna

·

Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co., ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna

422 Melanoma

INDEX A Abdomen ......60, 161, 199, 350, 351, 398, 405, 408, 410, 411 Aberrant...............................................133 Accommodation...................................214 Acetaminophen......................................70 Acne ......................................32, 166, 419 Adenovirus...........................................151 Adolescence ................207, 351, 397, 412 Allogeneic ....................154, 172, 180, 186 Alum ......................................................87 Anesthesia...........................................220 Angiogenesis ......111, 159, 240, 397, 403, 417, 418 Antiproliferative............................188, 193 Antiviral ........................................350, 406 Anus ........................59, 60, 172, 401, 415 Apoptosis ....129, 131, 132, 134, 135, 137, 158, 169, 174, 175, 230, 339, 361 Arterial ...........................................14, 151 Ascites .................................................339 Aspiration...............................34, 150, 399 Assay...........................................134, 175 Astrocytoma.................177, 178, 198, 404 Asymptomatic ......................................189 Autoantigens........................................186 Autologous....... 125, 139, 159, 174, 186, 261, 264, 268, 272 Autopsy................................................120 B Bacillus ................................................181 Bevacizumab .........................................66 Biochemical .................199, 350, 407, 412 Bladder ................................111, 279, 419 Bleomycin ............................................148 C Calcium........................................355, 356 Camptothecin ......................338, 340, 362 Capillary...............................................158 Capsules..............................................357 Carbohydrate...............................198, 356 Carboplatin ..................................296, 413 Carcinogen ..........................................138 Carcinogenesis....................................155 Carmustine .....70, 81, 147, 266, 267, 270, 271 Ceramide .............................................153 Cervical....47, 59, 278, 279, 280, 386, 400 Cervix ......................59, 60, 278, 400, 411 Chemoprevention ........131, 134, 135, 142 Chlorofluorocarbons ............................212

Cholesterol.................. 161, 354, 356, 404 Chondrosarcoma .......................... 83, 190 Chromosomal ............. 138, 168, 351, 418 Chromosome ...... 122, 143, 332, 351, 418 Chronic.... 34, 35, 117, 292, 376, 402, 414 Cisplatin ...... 68, 141, 147, 174, 267, 269, 271, 273, 296, 334, 362, 413 Colon...... 59, 75, 173, 185, 198, 222, 278, 280, 292, 401 Colorectal............................ 186, 279, 280 Conjunctiva ................................. 390, 401 Constitutional ...................................... 197 Corpus ................................................ 279 Cryosurgery ...... 25, 26, 29, 119, 282, 284 Cryotherapy .......... 34, 117, 118, 233, 401 Curative......... 49, 118, 259, 262, 365, 410 Curettage ...... 25, 117, 118, 238, 282, 284 Cyclophosphamide ............................. 360 Cysteinyldopa ............................. 148, 359 Cytokines ............................................ 129 Cytosine .............................................. 361 Cytotoxic ............. 139, 174, 194, 266, 270 D Dacarbazine... 68, 73, 147, 148, 152, 172, 195, 226, 228, 266, 267, 268, 269, 270, 271, 272, 273, 362 Degenerative ...................................... 355 Dendritic................................ 93, 153, 237 Dermatologist...... 131, 213, 220, 282, 284 Dermatology.......................... 38, 123, 131 Dermatosis.......................................... 286 Dexamethasone.......................... 170, 192 Diarrhea .............................................. 354 Doxorubicin ......................................... 230 Dysplasia ............................................ 247 E Eczema ................................. 32, 224, 416 Electrodesiccation...... 25, 117, 238, 282, 284 Electroporation............................ 301, 403 Endogenous.......................... 34, 141, 402 Epidemic ............. 118, 132, 165, 173, 417 Epidemiological........................... 126, 213 Epidermal............................ 179, 297, 420 Epidermis ...... 11, 12, 34, 161, 184, 198, 224, 247, 402, 403, 405, 416 Epithelial ..................................... 158, 185 Esophageal ......................................... 279 Etoposide ............................ 332, 334, 339 Exogenous ............ 34, 126, 161, 402, 403 Extracellular ........................................ 158

Index 423

Extravascular.......................................158 Extremity......................................274, 275 F Fenretinide...................................134, 135 Fetus....................................................355 Flavopiridol ............................................74 Fluorouracil....................25, 118, 321, 407 Folliculitis .............................................286 Fractionation........................................275 G Gastrointestinal......................33, 270, 398 Gemcitabine ........................................361 Gemfibrozil ..........................................131 Genotype .....................................164, 412 Ginseng ...............................................347 Glioblastoma........................................173 Glioma .................................................179 Glycoprotein ................154, 339, 350, 407 Granulocyte .........................159, 162, 360 Granuloma...........................................143 Groin ............................................120, 224 H Hematogenous ....................................245 Histamine.......................78, 141, 159, 398 Histology......................................256, 261 Hybridization................................169, 191 Hyperpigmentation ........................34, 403 Hyperplasia..........................................247 Hypoxia................................................147 I Immunity ......110, 128, 130, 172, 180, 405 Immunization ......128, 130, 162, 180, 185, 237, 405 Immunoglobulin ...................................136 Immunohistochemistry ................256, 261 Immunology ...........................33, 205, 397 Immunosuppression ....................117, 122 Immunosuppressive ............................220 Immunotoxins ......................................337 Indicative .....................................175, 419 Indolent................................................193 Induction .....110, 128, 129, 133, 153, 170, 181, 191, 196, 273, 339, 405 Infiltration .............................121, 181, 246 Infusion ....................72, 79, 110, 195, 406 Inoperable............................................329 Intermittent.............25, 202, 237, 268, 272 Interstitial .............................................130 Intravenous....... 100, 110, 226, 331, 336, 361, 406 Invasive .......133, 184, 187, 192, 247, 312 Ipsilateral .............................................120 Iris ........................83, 85, 86, 87, 110, 407 K Keratoacanthoma ................................117 Keratosis............25, 27, 28, 117, 120, 121

L Lectins................................. 335, 351, 420 Lethal .......................... 133, 173, 194, 207 Leukapheresis ...................................... 93 Leukemia ..... 81, 127, 186, 198, 279, 292, 402 Leukoplakia........................................... 28 Lipid .................................... 131, 161, 404 Localization ................. 136, 182, 296, 405 Lomustine ........... 148, 266, 270, 296, 411 Lymphadenectomy .... 248, 250, 255, 257, 258, 260, 266 Lymphocyte... 72, 134, 150, 163, 186, 409 Lymphocytic ................................ 181, 246 Lymphoma .. 162, 198, 279, 292, 402, 406 Lymphoscintigraphy.................... 149, 257 M Macrophage ........................ 154, 159, 162 Malignancy... 40, 117, 133, 190, 195, 203, 207 Mammography...................................... 47 Mania .................................................. 333 Manifest .............................................. 138 Mediator .............................................. 172 Medullary ............................................ 173 Melanin .... 11, 35, 60, 110, 149, 160, 166, 172, 173, 177, 402, 407, 409, 419 Melanosis.............................................. 41 Melphalan ............. 80, 253, 265, 274, 333 Membrane.. 154, 184, 186, 205, 350, 390, 401, 407, 415 Meninges ............................................ 182 Mesenchymal...................................... 185 Metabolite ........................................... 357 Microscopy.................................. 116, 120 Millimeter... 25, 30, 35, 120, 251, 252, 410 Molecule..... 136, 163, 165, 176, 178, 184, 187, 189, 194, 410, 415 Monocyte ............................................ 130 Morphogenesis ................................... 190 Morphology ................. 109, 158, 190, 405 Mutagenesis ....................................... 138 Myeloma ............................................. 279 N Nausea................................................ 329 Necrosis ........ 80, 227, 253, 265, 274, 337 Neoplasm............ 118, 166, 172, 183, 419 Neural ...... 137, 151, 176, 178, 187, 193, 244, 355 Neuroblastoma ................... 173, 176, 179 Niacin .................................................. 355 Nitrogen .............................. 119, 295, 397 Nitrosoureas................ 266, 270, 296, 411 Non .. 5, 18, 115, 126, 134, 142, 166, 172, 188, 189, 193, 278, 294, 308, 324, 329, 419

424 Melanoma

Nonmetastatic......................................137 O Occult ..........................175, 255, 257, 258 Oligopeptides.......................................171 Oncogene ............137, 164, 174, 292, 411 Oncologist......................................60, 411 Oncology .......................................18, 168 Osteosarcoma .......................................83 Ovalbumin ...........................................237 Overdose .............................................355 P Paclitaxel .....................................195, 336 Palliative ................49, 120, 265, 274, 275 Pancreas ......60, 160, 186, 199, 217, 351, 397, 399, 411, 416 Pancreatic............199, 279, 292, 329, 411 Papillary.......................................247, 251 Pathologist...................................244, 246 Peptide ....... 87, 150, 187, 188, 190, 192, 199, 226, 229, 413 Perfusion ..14, 35, 80, 119, 162, 223, 253, 265, 274, 275, 333, 361, 405, 412 Perineal .......................................188, 193 Pharmacodynamics .............................195 Pharmacokinetics ................................337 Pharmacologic.....................................135 Pharynx ...............................................279 Phenotype ..136, 138, 164, 169, 185, 190, 191, 207, 412 Phenylalanine ......................................359 Phosphorous .......................................356 Pityriasis ..............................................286 Plasma .......93, 110, 160, 168, 296, 402, 410, 412 Platelets .................................93, 111, 416 Platinum.......109, 266, 271, 321, 400, 401 Polypeptide..........171, 179, 186, 198, 405 Polyvalent ............................................180 Potassium............................................356 Precancerous ............25, 27, 29, 164, 413 Preclinical ....................127, 205, 209, 313 Precursor .............133, 166, 351, 412, 419 Premalignant .................35, 117, 118, 413 Preoperative ........................................169 Prevalence...........................................280 Proportional .........................................251 Protease ..............................................194 Pruritus ................................120, 224, 416 Psoralen ......................................122, 202 Psoriasis ........................32, 122, 164, 414 Psychiatric ...........................................331 Psychotherapy.............................323, 328 Pyogenic ..............................................143 Pyrazoloacridine ....................................83 R Radiodermatitis......................................28

Radiotherapy ..... 165, 187, 193, 252, 265, 275, 414 Receptor .... 126, 128, 135, 137, 142, 150, 152, 158, 187, 192, 336 Recombinant....... 92, 160, 170, 191, 253, 268, 272, 337, 402 Rectal.......................................... 187, 193 Rectum... 59, 60, 197, 198, 278, 280, 398, 401, 415 Recurrence .. 73, 119, 160, 168, 179, 182, 229, 245, 254, 256, 259, 262, 270, 274, 400 Refractory ............. 82, 184, 226, 227, 266 Regimen....... 71, 87, 169, 195, 197, 226, 252, 258, 259, 260, 262, 263, 265, 266, 267, 270, 271, 272 Registries ............................................ 279 Relapse ....... 82, 232, 234, 245, 252, 259, 260, 261, 262, 263, 264, 333 Remission ... 172, 179, 180, 199, 273, 415 Resected.... 151, 227, 252, 253, 259, 260, 262, 263, 264 Resection ... 128, 144, 168, 253, 254, 256, 262, 266, 270, 331 Retina.......................... 351, 365, 415, 419 Retinoid....................................... 134, 135 Retrospective ...................................... 258 Rheumatoid......................................... 155 Riboflavin ............................................ 354 S Sarcoma....... 79, 83, 110, 148, 159, 179, 279, 334, 411 Sargramostim ..................... 68, 80, 87, 91 Scabies ............................................... 224 Schwannoma ...................................... 154 Secretion.... 110, 154, 165, 183, 337, 405, 416 Selenomethionine ............................... 339 Serum 161, 168, 190, 226, 227, 230, 248, 404 Somatic ............................... 351, 397, 418 Species ...... 122, 159, 165, 166, 198, 397, 399, 416, 420 Sporadic...................... 136, 144, 147, 156 Stimulant ..................................... 110, 405 Stomach..... 199, 217, 279, 296, 397, 403, 404, 411, 412 Stool.............................................. 59, 401 Subclinical........................................... 175 Subcutaneous .... 128, 141, 178, 237, 247, 248 Substrate............................................. 190 Sunburn ...... 36, 118, 204, 221, 236, 285, 286, 416 Supplementation ................................. 339 Suppressive ................................ 170, 192

Index 425

Systemic ....... 14, 16, 128, 151, 166, 169, 172, 181, 183, 195, 245, 252, 253, 266, 270, 419 T Tamoxifen...147, 267, 268, 269, 271, 272, 273, 331, 360 Taxanes.......................................266, 271 Telangiectasia .....................................285 Telomerase..........................................336 Telomere .............................................336 Temozolomide .............67, 68, 85, 86, 141 Teratogenic..........................................131 Testicular .............................................279 Testis ...................................172, 297, 418 Thalidomide ...................................85, 232 Thermoregulation ................................354 Thyroid...60, 173, 279, 365, 366, 407, 418 Tolerance.....................117, 165, 179, 418 Tomography ........................................359 Topical .....25, 26, 117, 118, 134, 135, 284 Transplantation .......69, 72, 81, 162, 261, 264, 406 Treosulfan............................................361

Tretinoin ...................................... 134, 135 Tumour........................ 144, 148, 265, 359 Tyrosine ...................... 137, 187, 192, 336 U Ulceration.................... 244, 246, 247, 248 Unresectable......................................... 81 Urinary ................................................ 279 Urine ...... 59, 64, 93, 109, 160, 297, 365, 398, 399, 402, 415, 419 V Vaccination ................. 166, 229, 253, 419 Vaccinia ...................................... 142, 229 Vascular .............................. 147, 351, 419 Veins ................................................... 285 Vinblastine ............................ 68, 141, 362 Vincristine ........................................... 148 Vinorelbine .......................................... 331 Virus...................................................... 92 Visceral ....................................... 248, 275 Vitiligo ................................. 164, 286, 414 W Warts................................................... 284 Withdrawal .......................................... 197

426 Melanoma

The Official Patient's Sourcebook on Melanoma: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Intraocular Melanoma: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Botulism: A Revised and Updated Directory for the Internet Age

The 2002 Official Patient's Sourcebook on Psoriasis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Genital Candidiasis: A Revised and Updated Directory for the Internet Age

The Official Parent's Sourcebook on Ataxia Telangiectasia: A Revised and Updated Directory for the Internet Age

The 2002 Official Patient's Sourcebook on Shigellosis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Brainerd Diarrhea: A Revised and Updated Directory for the Internet Age

The Official Parent's Sourcebook on Adrenoleukodystrophy: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Balantidiasis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Coccidioidomycosis: A Revised and Updated Directory for the Internet Age

The 2002 Official Patient's Sourcebook on Psoriasis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Toxocariasis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Opsoclonus Myoclonus: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Shingles: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Penile Cancer: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Hansen's Disease: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Cerebral Atrophy: A Revised and Updated Directory for the Internet Age

The 2002 Official Patient's Sourcebook on Prolactinoma: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Macular Pucker: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Sjgren's Syndrome: A Revised and Updated Directory for the Internet Age

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The Official Patient's Sourcebook on Pheochromocytoma: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Bladder Cancer: A Revised and Updated Directory for the Internet Age

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The Official Patient's Sourcebook on Kaposi's Sarcoma: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Melanoma: A Revised and Updated Directory for the Internet Age

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The Official Patient's Sourcebook on Botulism: A Revised and Updated Directory for the Internet Age

The 2002 Official Patient's Sourcebook on Psoriasis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Genital Candidiasis: A Revised and Updated Directory for the Internet Age

The Official Parent's Sourcebook on Ataxia Telangiectasia: A Revised and Updated Directory for the Internet Age

The 2002 Official Patient's Sourcebook on Shigellosis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Brainerd Diarrhea: A Revised and Updated Directory for the Internet Age

The Official Parent's Sourcebook on Adrenoleukodystrophy: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Balantidiasis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Coccidioidomycosis: A Revised and Updated Directory for the Internet Age

The 2002 Official Patient's Sourcebook on Psoriasis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Toxocariasis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Opsoclonus Myoclonus: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Shingles: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Penile Cancer: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Hansen's Disease: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Cerebral Atrophy: A Revised and Updated Directory for the Internet Age

The 2002 Official Patient's Sourcebook on Prolactinoma: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Macular Pucker: A Revised and Updated Directory for the Internet Age

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The Official Patient's Sourcebook on Dry Mouth: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Prostatitis: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Ketamine Dependence: A Revised and Updated Directory for the Internet Age

The Official Patient's Sourcebook on Mdma Dependence: A Revised and Updated Directory for the Internet Age

The Official Parent's Sourcebook on Tourette Syndrome: A Revised and Updated Directory for the Internet Age

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The Official Patient's Sourcebook on Sjgren's Syndrome: A Revised and Updated Directory for the Internet Age

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