DOCETAXEL A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 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: Philip Parker, Ph.D. 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 for the diagnosis or treatment of a health problem. 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. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing 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., 1960Docetaxel: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00374-0 1. Docetaxel-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. 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, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on docetaxel. Books in this series 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 book. 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 Freeman 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 health books 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 ICON Health Publications.
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About ICON Health Publications 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
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON DOCETAXEL .............................................................................................. 3 Overview........................................................................................................................................ 3 Federally Funded Research on Docetaxel....................................................................................... 3 E-Journals: PubMed Central ....................................................................................................... 19 The National Library of Medicine: PubMed ................................................................................ 20 CHAPTER 2. NUTRITION AND DOCETAXEL .................................................................................... 39 Overview...................................................................................................................................... 39 Finding Nutrition Studies on Docetaxel...................................................................................... 39 Federal Resources on Nutrition ................................................................................................... 45 Additional Web Resources ........................................................................................................... 45 CHAPTER 3. ALTERNATIVE MEDICINE AND DOCETAXEL .............................................................. 47 Overview...................................................................................................................................... 47 National Center for Complementary and Alternative Medicine.................................................. 47 Additional Web Resources ........................................................................................................... 92 General References ....................................................................................................................... 93 CHAPTER 4. PATENTS ON DOCETAXEL ........................................................................................... 95 Overview...................................................................................................................................... 95 Patents on Docetaxel.................................................................................................................... 95 Patent Applications on Docetaxel.............................................................................................. 102 Keeping Current ........................................................................................................................ 112 CHAPTER 5. PERIODICALS AND NEWS ON DOCETAXEL ............................................................... 115 Overview.................................................................................................................................... 115 News Services and Press Releases.............................................................................................. 115 Academic Periodicals covering Docetaxel .................................................................................. 118 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................. 119 Overview.................................................................................................................................... 119 U.S. Pharmacopeia..................................................................................................................... 119 Commercial Databases ............................................................................................................... 120 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 123 Overview.................................................................................................................................... 123 NIH Guidelines.......................................................................................................................... 123 NIH Databases........................................................................................................................... 125 Other Commercial Databases..................................................................................................... 127 APPENDIX B. PATIENT RESOURCES ............................................................................................... 129 Overview.................................................................................................................................... 129 Patient Guideline Sources.......................................................................................................... 129 Finding Associations.................................................................................................................. 131 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 133 Overview.................................................................................................................................... 133 Preparation................................................................................................................................. 133 Finding a Local Medical Library................................................................................................ 133 Medical Libraries in the U.S. and Canada ................................................................................. 133 ONLINE GLOSSARIES................................................................................................................ 139 Online Dictionary Directories ................................................................................................... 139 DOCETAXEL DICTIONARY ...................................................................................................... 141 INDEX .............................................................................................................................................. 187
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FORWARD 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."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with docetaxel is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about docetaxel, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to docetaxel, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on docetaxel. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to docetaxel, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on docetaxel. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON DOCETAXEL Overview In this chapter, we will show you how to locate peer-reviewed references and studies on docetaxel.
Federally Funded Research on Docetaxel The U.S. Government supports a variety of research studies relating to docetaxel. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 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. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to docetaxel. 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 docetaxel. The following is typical of the type of information found when searching the CRISP database for docetaxel: •
Project Title: ANTI-TUMOR MECHANISMS & THERAPEUTIC EFFECTS OF VITAMIN D Principal Investigator & Institution: Johnson, Candace S.; Professor of Pharmaceutical Sciences And; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2003; Project Start 01-MAY-1995; Project End 28-FEB-2008
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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: (provided by applicant): Vitamin D, 1,25 dihydroxycholecalciferol (calcitriol) has significant antiproliferative activity in vivo and in vitro. Calcitriol induces G0/G1 arrest, modulates p27 and p21, induces cleavage of caspase 3, MEK, and PARP, inhibits P-Akt and significantly increases MEKK-1. In vitro and in vivo, dexamethasone (dex) potentiates calcitriol-mediated antitumor activity through the vitamin D receptor (VDR). In a phase II trial in androgen-independent prostate cancer (AIPC) with high dose oral calcitriol and dex, we observed a 50 percent reduction in serum prostate specific antigen (PSA) in 28 percent of patients. Also, calcitriol significantly enhances the in vitro and in vivo antitumor efficacy of platinum analogues and taxanes. Enhancement of drugmediated apoptosis by calcitriol is associated with an increase in PARP-, MEK- and caspase-cleavage, p73 and MEKK-1 with a decrease in P-Erk and P-Akt. Thus, we performed two phase I trials of calcitriol with either carboplatin or paclitaxel. From the pharmacokinetic (pk) data, increasing oral doses of calcitriol did not result in higher serum calcitriol levels; suggesting a potential decrease in bioavailability. In addition, calcitriol increases the expression of EGFR. When calcitriol is combined with the EGFR tyrosine kinase inhibitor, ZD 1839 ('Iressa'), a significant enhancement of antitumor activity is observed in vitro and in vivo associated with a significant decrease in P-Erk and P-Akt. Therefore, calcitriol has significant pro-apoptotic effects and can synergize with other cytotoxic modalities that potentially share the targets, P-Akt, P-Erk, MEKK-1 and/or p73. Therefore, we propose to examine the potential efficacy and mechanisms of calcitriol in combination with cytotoxic agents both clinically and pre-clinically by the following specific aims: 1) to determine the modulation of the molecular events of apoptosis in the calcitriol signaling pathway by platinum and taxanes in vitro and in vivo in tumor models; 2) to evaluate high dose intravenous (iv) calcitriol (QDx2, D1, 2), docetaxel (70mg/m 2, D2) and dex (QDx2, D1, 2) every 21 days in AIPC in a phase I/II clinical trial; 3)to determine the mechanisms involved in the enhanced antitumor activity of the tyrosine kinase inhibitor, ZD 1839 in combination with calcitriol in vitro and in vivo and 4) to examine in the Phase I setting ZD1839 250mg,QD) with escalating high iv doses of calcitriol weekly in patients with advanced cancer Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BENCH TO CLINIC IN CONCURRENT CHEMORADIATION THERAPY Principal Investigator & Institution: Choy, Hak; Professor and Chairman; Radiation Oncology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 29-SEP-2003 Summary: The principal investigator has a significant record in research that is both patient-oriented, and translational. A unique and important aspect of his career for the purposes of the K-24 Research Career Award is his continuous involvement with specific interventions beginning with pre-clinical work in the laboratory, and carrying through phases I, II, and III clinical trials. His primary research interest is in the study and development of new therapeutic agents that enhance the cell killing effects of radiation in cancer treatment. Current research projects involve bench studies of 4 agents that enhance the effects of radiation therapy-docetaxel, RFS-2000, RSR-13, and JM-216, all of which act by distinctly different mechanisms. Some studies involve a single agent and radiation therapy, while others involve a combination of chemotherapeutic agents together with radiation. Clinical studies involve three phase I studies of concurrent radiosensitizing agents and radiation therapy - docetaxel, irinotecan, and JM-216. One phase II study involves the allosteric modifier, RSR-13 and radiation therapy. All studies have been continuously supported through private
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pharmaceutical firm funding, and will continue to be so for the foreseeable future. He has initiated and stimulated a clinical research program in radiation oncology at the Vanderbilt Cancer Center, and was named Director of Clinical Research. Mentoring activities have been a consistent theme throughout his career, both at Brown University and at Vanderbilt. He initiated a fellowship program in radiation oncology clinical research using private funding, and has recruited 3 fellows into the program. Current mentoring activities involve 3 new faculty in the Vanderbilt Cancer Center. He initiated a mixed specialty symposium conference in concomitant chemoradiotherapy, which is continuing as a biennial conference. The K-24 Research Career Award will give the PI an opportunity to concentrate efforts on currently active clinical research projects, moving bench studies through to clinical trials, completing currently active clinical trials, and initiating studies on promising new agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BILIARY AND INTESTINAL CELL MODELS OF DRUG TOXICITY Principal Investigator & Institution: Kanz, Mary F.; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Recent, unprecedented expansion of candidate drugs has generated a critical need for early phase toxicity testing by in vitro assays that are rapid, sensitive, reproducible and cost effective There is a particular need for cytotoxicity assays that monitor injury to cholangiocytes, epithelial cells of bile ducts (BDC), or to enterocytes, epithelial cells of the small intestine (IEC). Although these sites are known targets of widely used anticancer drugs, in vitro assays have not been established due to the lack of appropriate cell systems The goal of the proposed research is to develop cytotoxicity assays using newly available cell systems and bile from drugtreated animals as a physiologically relevant way to expose the cells to reactive drug/metabolites, which is the most plausible route of exposure. The anticancer drugs [Iomustine (CCNU), methotrexate (MTX), docetaxel (DCT)] chosen to validate these in vitro cytotoxicity models have well-established toxicities to BDC or IEC in vivo, represent classes of drugs that work by different mechanisms, and are extensively excreted in bile. Our approach is based on preliminary studies indicating that bile from rats treated with the cholangiodestructive agent 4,4'-diaminodiphenylmethane (DAPM) is cytotoxic to primary rat BDC in vitro. Functional and morphological characteristics of DAPM-induced injury to bile ducts in vivo are virtually identical to the BDC injury produced in vitro. Bile from rats treated with the NSAID indomethacin has been reported to injure a rat intestinal cell line in vitro. A more differentiated cell line that forms villus-like enterocytes (Cdx-IEC-6 cells) is proposed as the model IEC system in this application. Our specific aims are (1) validate the target organ specificity of biliary drug/ metabolites to BDC versus IEC in vitro by viability assays and functional indices of cell injury, (2) characterize the specificity, reproducibility and high-throughput possibilities of sensitive assays for mitochondrial injury, paracellular permeability, ATP content, and membrane leakage as potential biomarkers of biliary drug/ metaboliteinduced dysfunction, and (3) determine if biliary drug/metabolites induce comparable early effects on gene expression in BDC and IEC in vivo versus in vitro using laser capture microdissection and gene chip analyses. The basic techniques developed in this research will lead to new methods for screening potential drug injury to target sites that are not easily investigated in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOMODULATION OF CAPECITABINE BY DOCETAXEL IN NONSMALL* Principal Investigator & Institution: Villalona, Miguel A.; Associate Professor; Internal Medicine; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2004; Project Start 22-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): The poor prognosis of patients with advanced lung cancer, with a median survival of less than 12 months, indicates an obvious need for more effective treatments. Although fluoropyrimidines are not commonly used to treat NSCLC, these agents have demonstrated improvements in survival in the adjuvant setting. The recently introduced oral fluoropyrimidine capecitabine is interesting for evaluation in NSCLC, given its synergistic potential in combination with paclitaxel or docetaxel, drugs that are among the most active in the treatment of NSCLC. This synergy is believed due to upregulation of the enzyme thymidine phosphorylase (TP), which is responsible for the preferential tumor activation of capecitabine. We have developed a novel schedule for the combination of docetaxel and capecitabine that takes into consideration the time dependency of TP upregulation by docetaxel. This schedule is aimed to provide for repetitive stimulation of TP, and for capecitabine administration at the predicted times of maximal TP upregulation. Using this schedule, we demonstrated activity in NSCLC previously treated with chemotherapy. Evaluation of TP, dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) expression m tumor blocks from a group of these patients suggested that TP tumor to normal and TP/DPD ratios, as well as tumor nuclear TS, may be useful as predictors of response to treatment. We propose to study this combination/schedule in NSCLC patients not previously treated with chemotherapy. Tumor and normal lung tissue will be evaluated for potential predictors of response to this combination. In addition, DPD activity in peripheral mononuclear cells will be measured to establish relationships to toxicity within the DPD normal distribution. The proposed research has the potential of identifying a new combination treatment for advanced NSCLC and providing a predictive approach to identify patients more amenable to treatment response to the combination. Confirmation of our working hypothesis may lead to a new treatment paradigm suitable for evaluation in the adjuvant setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BREAST CANCER Principal Investigator & Institution: Perez, Edith A.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Summary: The Breast Cancer Program of the NCCTG is committed to clinically meaningful research which addresses management issues important to women with all stages of this disease. There has also been an increased emphasis on laboratory correlative science studies. Patient accrual to treatment protocols has increased from 314 patients per year for the previous five-year grant period to 484 patients per year during the current grant period. Sixteen manuscripts and ten abstracts have been published since January 1, 1996. The major accomplishments of the Breast Program fall into four areas: 1) new hormonal therapy approaches for metastatic breast cancer (MBC): We demonstrated the anti-tumor activity of two dose schedules of letrozole; the lack of pharmacokinetic interaction between tamoxifen and letrozole; co-sponsored a Breast Intergroup study demonstrating similar benefit for medical versus surgical castration in pre-menopausal patients; 2) New chemotherapy approaches for MBC. We demonstrated
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the significant anti-tumor activity of the combination of paclitaxel plus carboplatin; the activity of different sequential schedules of AC-docetaxel chemotherapy in a randomized phase II trial which also included translational analysis of soluble Her-1 and Her-2 receptors; co- sponsored the PBT-1 intergroup trial which demonstrated a lack of survival improvement for patients receiving high dose chemotherapy with stem cell support versus conventional chemotherapy; and co-sponsored the E1193 Intergroup trial which demonstrated improved response rate and time to progression with the concurrent use of paclitaxel and adriamycin instead of the sequential use of these agents; 3) New radiotherapy approaches: We demonstrated the feasibility of hyperfractionated radiotherapy with shortening of therapy to three weeks with and without doxorubicin for patients with early stage breast cancer; 4) Adjuvant therapy: We cos-sponsored three Intergroup trials, INT 0100 which demonstrated the improvement in disease-free survival and overall survival of adjuvant chemotherapytamoxifen versus tamoxifen alone for post-menopausal patients with node positive breast cancer, and studies S9313 and C9741 which evaluated chemotherapy sequence and dosing in node (+) or node (-) breast cancer. Future plans: 1) Hormonal therapy for MBC: Evaluation of the activity of tamoxifen plus tratuzumub in patients with ER (-) metastatic breast cancer (with translational evaluation of solubl4e Her-1 and Her-2 receptors) and of the pure anti-estrogen Faslodex as third-line hormonal therapy; 2) New chemotherapy approaches for MBC: We will coordinate the N9931 Intergroup trial to evaluate whether the monoclonal antibody trastuzumab enhances the efficacy of chemotherapy in patients with lower degrees (+1, +2) of Her-2 expression (including quality of life analysis and correlative science studies), the study of a combination of docetaxel and carboplatin as first-line therapy (along with translational evaluation of genetic polymorphisms that may be associated with response and toxicity); the evaluation of MTA plus gemcitabine; the valuation of topical ceramides and quality of life for patients with cutaneous metastasis from breast cancer; and completion of our ongoing trials of dolastatin-10, irinotecan, and the combination of oral etoposide with intravenous paclitaxel for advanced breast cancer, as well as the optimization of schedule for paclitaxel, carboplatin, and trastuzumab for patients with higher Her2-2 (+3) expression; 3) Adjuvant therapy: We will coordinate the new Breast Intergroup adjuvant. The development of other novel therapeutic approaches, including immunotherapy and other biological therapies with appropriate correlative translational studies, is ongoing. The accomplishments and future plans of the Breast Program address the major research themes of the NCCTG as a whole; i.e., novel therapeutics, phase II trials, translational research, participation and coordination of national intergroup studies, quality of life, and active involvement of community physicians in all aspects of trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANCER AND LEUKEMIA GROUP B--PET COMMITTEE Principal Investigator & Institution: Ratain, Mark J.; Professor of Medicine and Chairman; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-APR-1986; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract): The overall objectives for the Pharmacology and Experimental Therapeutics (PET) Committee of the CALGB are to study population pharmacokinetics and pharmacodynamics of new and established anticancer agents in a multi-institutional setting; to introduce new drugs and combinations, including immunomodulatory and cytostatic agents into the CALGB for eventual phase II and III testing; to initiate and conduct a program of mucositis
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prevention in the CALGB; and to organize educational symposia for the Group on topics in cancer pharmacology and experimental therapeutics. The committee meets twice annually in addition to sponsoring an educational session at each of the full Group meetings. Population pharmacology are ongoing of suramin, carboplatin, paclitaxel, 9aminocamptothecin, 5-fluorouracil and etoposide. Studies are planned of irinotecan and docetaxel, in addition to two additional studies of paclitaxel with regard to the effects of age and body surface on toxicity and pharmacokinetics, Other special populations to be studied include race (docetaxel and irinotecan) and end-organ dysfunction (gemcitabine, irinotecan). Two novel therapeutic studies involving biologics are planned, including IL-2 in combination with an anti-HER-2 monoclonal antibody and interferon alpha in combination with tamoxifen. Another new initiative is a program to prevent mucositis. The initial study will evaluate the effect of IL-11 on mucositis secondary to cisplatin, 5-FU and leucovorin. Since many of the studies include analysis of pharmacological specimens, the Committee utilizes three core laboratories--at the University of Chicago, the University of Maryland and the University of Tennessee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOTHERAPY WITH DOXORUBICIN AND DOCETAXEL IN OPERABLE STAGE I BREAST CANCER Principal Investigator & Institution: Baker, Laurence H.; Professor of Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CISPLATIN, DOCETAXEL, RADIATION THERAPY FOR NSCLC Principal Investigator & Institution: Mudad, Raja; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL TRIALS OF FLAVOPIRIDOL WITH CHEMOTHERAPY Principal Investigator & Institution: Schwartz, Gary K.; Associate Professor of Medicine; Sloan-Kettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2004; Project Start 01-AUG-1996; Project End 28-FEB-2009 Summary: (provided by applicant): R01 CA67819, entitled "Clinical Trials of Flavopiridol with Chemotherapy", has been devoted to the clinical development of the cyclin dependent kinase inhibitor flavopiridol in combination with chemotherapy in the treatment of advanced human cancers. This program is based on discoveries made in our laboratory that flavopiridol enhances the induction of apoptosis by a broad range of chemotherapeutic agents. Based on the strength of our laboratory and clinical data, we initiated our R01 supported phase I clinical trial of sequential CPT-11 and flavopiridol with surrogate markers of response, a phase II clinical trial of sequential paclitaxel and flavopiridol in patients with paclitaxel refractory, metastatic esophagus cancer, and further laboratory studies to identify potential surrogate markers for response with the CPT-11 and flavopiridol combination. We have not only achieved these aims but have
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also considerably exceeded them. In particular, we have completed both of these phase I and II clinical trials, have successfully evaluated a series of molecular markers and correlated them to response, have identified new biomarkers (including drg1), have made considerable laboratory progress in identifying new flavopiridol combinations, and are in the process of translating these laboratory studies into clinical cancer research. Based on our laboratory and clinical results, this grant renewal will represent a focused approached to the continued development of flavopiridol. In particular, we plan to test flavopiridol, as an agent that enhances the effect of CPT-11, and develop flavopiridol with chemotherapy and radiation in the treatment of pancreatic cancer. The specific aims of this R01 grant renewal will be to: 1. Complete the current phase I trials of flavopiridol in combination with CPT-11-based chemotherapy, with continued testing of biomarkers of response. This includes CPT-11 and cisplatin (MSKCC IRB# 02043/NCI # 5700) and CPT-11 as part of the FOLFIRI regimen (MSKCC IRB # 02-024, NCI #5757). 2. Develop a clinical program of flavopiridol-modulated therapy with radiation (MSKCC IRB # 02-034/NCI # 5764) gemcitabine (MSKCC IRB # pending/NCI # 6051), and docetaxel (NCI LOI#6366) for the treatment of both locally advanced and metastatic pancreas cancer, and 3. Continue to examine the mechanisms by which flavopiridol potentiates CPT-11 induced apoptosis, which should provide the opportunity to identify new biomarkers of response for these flavopiridol drug combinations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--ANALYTICAL PHARMACOLOGY LABORATORY Principal Investigator & Institution: Hohl, Raymond J.; Professor of Internal Medicine and Pharm; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2008 Summary: The HCCC Analytical Pharmacology Laboratory is currently supported by HCCC, other research endowment funds, and contracts with cooperative groups for specific projects, but has no NIH funding as a Core facility. All the needed equipment is currently available. Support from the NCI for operating expenses will allow this facility to grow and support peer reviewed research exploring the effect of aging on the pharmacology of anti-neoplastic drugs as outlined in the "Aging and Cancer Therapeutics" thematic area. An example of such research is the potential pilot study described that will be led by Dr. Shane Scott. The project explores whether cognitive changes in elderly subjects with breast cancer being treated with doxorubicin, cyclophosphamide and docetaxel are associated with cognitive changes associated with chemotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOCETAXEL & METASTATIC BREAST CANCER
TRASTUZUMAB
IN
HER2
EXPRESSING
Principal Investigator & Institution: Foss, Francine M.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENHANCEMENT OF AD-P53 THERAPY WITH INTRATUMORAL TAXANE Principal Investigator & Institution: Yoo, George H.; Otolaryngology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 03-JUL-2003; Project End 30-APR-2005 Summary: (provided by applicant) The ultimate objective of this project is to determine the ability of locally delivered docetaxel to enhance Ad-p53 antitumor activity in head and neck squamous cell carcinoma (HNSCC). Docetaxel and Ad-p53 will be delivered intratumorally and into surgical wounds. In this proposal we plan preclinical in vivo experiments in order to develop clinical trials using this approach. This is a high risk and high impact project that uses a novel approach to aggressively treat local-regional disease. In advanced HNSCC, the five-year survival rate is less than 40 percent. Since patients with advanced HNSCC have a high rate of local-regional failure (40-60 percent) with existing treatment modalities, aggressive local therapy approaches need to be developed. A higher intratumoral concentration produces a greater cytotoxic effect since tumor cell death is proportional to drug concentration. Intratumoral (IT) chemotherapy focuses high drug concentrations in solid tumors and limits total body exposure to the cytotoxic agent resulting in increased dose-related tumor cell killing and reduced toxicity. Our previous in vitro data show that docetaxel enhances Ad-p53 apoptosis in HNSCC cells in part by increasing viral transduction via upregulation of the coxsackieadenovirus receptor. We have significant experience with gene therapy since we were investigators in the Ad-p53 Phase II trial along with the Phase I and II E1A-liposome gene therapy trials and are now participating in two Phase III and a Phase II perioperative trial (SWOG: S0011, PI: G. Yoo) using intra-wound (IW) injections of Adp53. Before we begin clinical trials using intratumoral (IT) and intra-wound injections (IW) of docetaxel and Ad-p53, we propose in vivo preclinical experiments to test this treatment approach. Using human HNSCC cell lines and a mouse xenograft model, we will establish the optimum dose and the activity of IT docetaxel when combined with IT Ad-p53. Furthermore, we will monitor alterations in expression of key biomarkers. Since we also want to develop delivery of docetaxel + Ad-p53 by perioperative injections, we will determine the tumor growth in a microscopic residual model and surgical wound healing toxicity using IW docetaxel and Ad-p53. Favorable data from the proposed project will lead to the development of clinical trials using intratumoral and intrawound injections of docetaxel and Ad-p53. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GEMZAR: RADIOSENSITIZATION
MECHANISMS
OF
CYTOTOXICITY
&
Principal Investigator & Institution: Shewach, Donna S.; Professor; Pharmacology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 08-JUL-1999; Project End 30-JUN-2008 Summary: (provided by applicant): Previously we hypothesized and then proved that 2',2'-difluoro-2'-deoxycytidine (dFdCyd, gemcitabine) is a potent radiation sensitizer. During the current grant period we demonstrated that radiosensitization correlated strongly with inhibition of ribonucleotide reductase by the 5'-diphosphate of dFdCyd, resulting in greater than 80 percent depletion of dATP, whereas the 5'-triphosphate contributed primarily to the cytotoxic effect. Cells that were radiosensitized by dFdCyd accumulated in the less radiosensitive S-phase during drug exposure. Radiosensitization
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did not require apoptotic cell death, and it could occur in p53 wild-type as well as mutant p53 cell lines. Gemcitabine did not increase DNA double strand breaks prior to or following irradiation, nor did it inhibit their repair. Thus, the accumulated data suggest that radiosensitization with dFdCyd is determined by the nature of the DNA damage sustained prior to irradiation rather than the response to DNA damage after irradiation. We now hypothesize that the critical lesion for radiosensitization with dFdCyd is the incorporation in DNA of an incorrect nucleotide caused by the depleted dATP and, if this lesion is not repaired prior to S-phase, irradiation will prevent repair of the misincorporation events resulting in permanent mutation and enhanced cell death. This hypothesis would predict that cells defective in repairing misincorporated nucleotides, such as mismatch repair deficient cells, would be better radiosensitized than cells proficient in this pathway. Preliminary data indicate that mismatch repair deficient HCT-116 cells are radiosensitized by dFdCyd whereas the mismatch repair proficient counterpart was not, although it was more sensitive to cytotoxicity with dFdCyd. We propose to evaluate the factors that determine dFdCyd cytotoxicity and radiosensitivity in isogenic cell lines defective or proficient in mismatch repair. Using a shuttle vector assay, we will determine whether the hypothesized radiosensitizing lesions, misincorporated nucleotides, are more prevalent in cells that are radiosensitized by dFdCyd. In addition to defining the mechanism of radiosensitization for dFdCyd, we will also determine the mechanism of synergy when it is combined with docetaxel, based on high antitumor efficacy reported recently in patients. Preliminary data demonstrate that this synergy is not related to the ability of docetaxel to block cells in G2/M, but rather we hypothesize docetaxel commits dFdCyd-treated cells to S-phase specific cell death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL MODULATION OF TAXOL ACTION IN SOLID TUMORS Principal Investigator & Institution: Fan, Weimin; Professor; Pathology and Lab Medicine; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (PROVIDED BY APPLICANT): Taxol, a naturally occurring antimitotic agent, has shown significant cell-killing activity against tumor cells by induction of apoptosis. However, the mechanism of taxol mediated cell death and its relationship with taxol's well-known effects on microtubules and mitotic arrest is not entirely clear. Recent studies in this laboratory demonstrated that taxol's cell-killing activity (but not mitotic arrest) is selectively inhibited if tumor cells were pretreated with glucocorticoids, suggesting that taxol-induced apoptosis might occur via a signaling pathway independent of mitotic arrest. On the other hand, since glucocorticoids (such as dexamethasone) are routinely used in the clinical application of taxol to prevent hypersensitivity reactions and other adverse effects, this finding also raises a clinically relevant question as to whether the pretreatment with glucocorticoids might interfere with taxol's antitumor efficacy. The objectives of this proposal are to elucidate the mechanism by which glucocorticoids inhibit taxol-induced apoptosis and determine its potential influence on taxol's therapeutic effect. Meanwhile, utilizing the unique inhibitory effect of glucocorticoids on taxol's action, this proposed research also tries to determine the molecular basis of taxol-induced apoptosis via a "gene-directed" pathway. Therefore, this research application will pursue two major specific aims. Aim 1 is to evaluate the potential inhibition of glucocorticoids on taxol and docetaxel's therapeutic effects in vivo through establishment of appropriate animal models. This aim will
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confirm or negate the implication of glucocorticoid's effect on taxol or docetaxel's administration in vivo. Aim 2 is to investigate the molecular mechanism underlying taxol-induced apoptosis and glucocorticoid-mediated drug resistance. Based on the latest progress, this study will focus on elucidating the possible role of the NF-kB/IkBalpha signaling pathway in the regulation of apoptotic cell death induced by taxol and possibly other antimitotic agents in human solid tumor cells. The long-term goal of this research is to provide molecular insight into the mechanism and signal pathways that lead to taxol-induced cell death and glucocorticoid-mediated drug resistance. The information obtained from this proposed research may prove valuable for improving in the clinical application of this class of antineoplastic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IAPS AS NOVEL TARGETS FOR CANCER THERAPY Principal Investigator & Institution: Yang, Lily; Winship Cancer Institute; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Defects in apoptosis signaling pathway and upregulation of apoptosis inhibitory factors confer resistance of human cancer cells to therapeutic agents. A promising strategy to overcome the resistance is to target apoptosis machinery directly. Increasing evidence indicates that inhibitor-of-apoptosis proteins (IAPs) are upregulated in human tumor cells. We found that expression of IAP counteracting protein genes, such as dominant negative survivinT34A mutant, XIAP associated factor 1 (XAF1) and active Smac, induce apoptotic cell death preferentially in tumor cell lines but have no apparent effect on normal cell lines. To determine the molecular bases of the differential apoptotic response in tumor and normal cell lines, we examined the levels of apoptotic and anti-apoptotic factors in human cancer and normal cell lines. We found that many human cancer cell lines have constitutively activated caspase activities and yet are not undergoing apoptosis. We also detected high levels of IAPs, such as survivin and XIAP, in the tumor cell lines. Based on these observations, we hypothesize that the presence of constitutively activated caspases and upregulated IAPs in human tumor cells, but not in normal cells, confers selectivity in induction of apoptotic cell death in tumor cells by expression of survivinT34A, XAF1 and/or active Smac genes. A combination of downregulation of IAP function with chemotherapy agents further enhances anti-tumor effects in tumor cell lines as well as in human tumor xenograft models. To test the hypothesis, we will determine whether constitutively activated caspases are required for selective induction of apoptosis in tumor cell lines by expression of LAP counteracting protein genes in the presence of caspase inhibitors or with co-expression of an autocatalytic Rev-caspase 3 gene. We will further determine whether apoptosis can be induced in normal cell lines by expressing IAP counteracting protein genes when the cells are engineered to express high levels of both activated caspase 3 and XIAP. Since human tumor cells express high levels of survivin and XIAP, it is necessary to inhibit the function of both proteins to release the blockage of IAPs on the apoptotic pathway. In the proposed study, we will determine the most effective combination of lAP counteracting protein genes to achieve maximum apoptosis induction in human tumor cells. Finally, we will determine whether a combination of expression of IAP counteracting protein genes with chemotherapy drug docetaxel or HSV-TK/GCV suicidal gene therapy increases the anti-tumor effect in human breast and pancreatic cancer cell lines as well as in human tumor xenograft models. Results from this research should allow us to determine if IAPs are novel molecular targets for the development of cancer-specific therapeutic approaches.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VIVO EPR IMAGING OF REDOX STATUS AND THIOLS IN TUMOR Principal Investigator & Institution: Kuppusamy, Periannan; Associate Professor of Internal Medicine; Internal Medicine; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Ovarian Cancer is the fifth leading cause of death among women in the United States. Early stages of this disease are usually asymptomatic with high malignant potential. Due to lack of adequate diagnostic techniques, the disease is usually detected at late stages. Surgery is used for debulking followed by chemotherapy as a supplemental treatment modality. Platinum-based complexes (for example, cisplatin, carboplatin) in combination with natural products (e.g. paclitaxel, docetaxel) are the primary chemotherapeutic agents used in the treatment of ovarian cancer. However, a major limitation to the success of the platinumbased chemotherapeutic regimen is the frequent development of drug resistance in the recurrent tumor. Evidences suggest that increased cellular thiol levels are associated with the reduced sensitivity of tumor cells to cisplatin. Therefore, a reliable and noninvasive method to determine the thiol level in the tumor should be a useful adjunct for the clinical oncology, pharmacology and chronotherapy of ovarian cancer. The objective of this proposal is to develop and apply electron paramagnetic resonance (EPR) spectroscopy and imaging techniques to measure tumor redox status, including thiol levels, in vivo. The EPR technique has the unique advantage of direct and noninvasive detection of overall redox as well as thiol redox in tissues. In addition, reliable and accurate in vitro measurements can be performed in cell suspension and biopsy tissues with ease of preparation and minimum processing. Preliminary data on in vitro cellular systems and in vivo murine tumor models show that the thiol levels can be measured and imaged utilizing EPR spectroscopy. The specific aims are: 1. Development of an in vitro EPR technique to perform measurement of intracellular thiols in human ovarian cancer cells; 2. Development of in vivo EPR techniques to perform non-invasive imaging of redox status and thiols of normal tissue and tumor in mice; 3. Monitoring thiol levels in ovarian cancer cells before, during and after treatment with platinum antitumor drugs and taxanes; 4. In vivo measurement and imaging of thiols in human ovarian cancer cells grown as solid tumor xenografts in athymic nude mice. The results will enable a better understanding of the development of drug resistance in ovarian cancer and offer efficient diagnosis for effective treatment of ovarian cancer patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIPOSOMAL BCL-2 ANTISENSE THERAPY FOR SOLID TUMORS Principal Investigator & Institution: Esteva, Francisco J.; Breast Medical Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 04-SEP-1999; Project End 31-AUG-2004 Summary: The objective of this career development award is to provide the candidate, Dr. Francisco J. Esteva, the experience and knowledge necessary to direct an independent patient-oriented research program. Dr. Esteva is a medical oncologist with five years of clinical training and two years of basic research training, including experience with animal models of human breast cancer. He currently devotes 20 percent
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Docetaxel
of his effort to research and 80 percent to clinical activities. This award would enable the candidate to increase his research effort to 75 percent. The specific aim of this proposal are: (1) to determine the pharmacokinetics, dose-limiting toxicity, maximum tolerated dose (MTD), or biologically active dose (BAD) of liposomal antisense to Bcl-2 (L-Bc1-2 AS) for patients with solid tumors; (2) to determine the efficacy of L-Bcl-2 AS in combination with docetaxel for patients with breast cancer resistant to paclitaxel; and (3) to investigate the efficacy of docetaxel, paclitaxel and doxorubicin in combination with L-Bcl-2 AS in animal models of human breast cancer. Research design and methods. Dr. Esteva will conduct a phase I trial of L-Bcl-2 AS in patients with metastatic solid tumors. The MTD is defined as the dose at which two of six patients experience grade 3 or higher toxicity. BAD is defined as the dose associated with a 50 percent reduction in Bcl2 expression in circulating lymphoma cells (flow cytometry) or a 50 percent reduction in Bcl-2 expression in tumor biopsies (immunohistochemistry or western blot). It is anticipated that this study will accrue 21-24 patients in approximately 24 months. The second aim will be addressed by a phase I/II clinical trial. Efficacy will be measured by the rate of response. The trial will be conducted in two stages. Thirteen patients will be entered in the first stage and 30 in the second stage, for a total of 43 patients. It is anticipated this study will take approximately three years. The trial design assumes type I and type II error rates of 5 percent and 20 percent, respectively. Human breast cancer MCF-7 xenografts will also be developed in nude mice and Severe Combined Immunodeficiency (SCID) mice. MCF-7 cells overexpressess Bcl-2 and grow readily as xenografts in mice. The Candidate will be supervised by Dr. Gabriel Hortobagyi (Department of Breast Medical Oncology) and Dr. Gabriel Lopez-Berestein (Department of Bioimmunotherapy). M. D. Anderson Cancer Center has the patients and resources necessary for Dr. Esteva to successfully complete this research project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LY231514 & DOCETAXEL DOSING IN CANCER Principal Investigator & Institution: Roberts, John Commonwealth University Richmond, Va 232980568
D.;
Professor;
Virginia
Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF ACTION OF HERCEPTIN R IN BREAST CANCER Principal Investigator & Institution: Chang, Jenny C-N.; Associate Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-APR-2003 Summary: (Applicant's Abstract) The HER-2 neu proto-oncogene product is overexpressed in 20 percent to 30 percent of breast cancers and is associated with a worse clinical outcome. Clinical evidence in patients with metastatic breast cancer demonstrates that interference with HER-2 by a new recombinant DNA-derived humanized monoclonal antibody, rhumMabHer-2 (Herceptin) can lead to clinical responses. To further develop the clinical use of Herceptin, it would be important to define its efficacy in earlier stage disease, where cure is still possible. Although the cellular mechanisms of action are not fully understood, this targeted biologic therapy directed at a molecular determinant of breast cancer represents a promising prototype for improving the efficacy of anti-cancer treatment. The applicant expects that greater understanding of the cellular response to Herceptin will provide insight on the optimal
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clinical use of this receptor-targeted strategy, and on the mechanisms of cellular resistance to HER-2 blockade. The understanding of the mechanism could also lead to the development of small molecules targeting the critical portion of the pathway important for therapeutic effect. This project has two specific aims. The first is to demonstrate the clinical efficacy of Herceptin when given with docetaxel as neoadjuvant therapy. The second is to define the mechanisms of the cellular response to Herceptin. For Specific Aim 1, the applicant proposes to perform a neoadjuvant clinical trial in patients with locally advanced HER-2 over-expressing breast cancers with weekly Herceptin given initially as a single agent for the first three weeks, followed by combination of weekly Herceptin and three-weekly docetaxel for 12 weeks before primary surgery. The final surgical specimen would be examined for histological complete response, and the rate of this response would serve as a validated surrogate marker of long-term efficacy. An increase in histological complete remission with this regimen when compared to historical controls would provide encouraging evidence of the greater potential of cure with Herceptin and docetaxel, especially in the adjuvant setting. For Specific Aim 2, sequential core biopsies of the primary breast tumors will be taken in patients enrolled in this clinical study. These patients will have biopsies taken at time of diagnosis, 24 hours after the first dose of Herceptin, and just prior to subsequent doses of Herceptin on days 8, 15, and 22. These core biopsies and the tumor specimens obtained at surgery will then be assessed for the effects of Herceptin by immunohistochemical analysis in the following areas: proliferation and cell cycle regulatory molecules (Ki67, p27, cyclin D1), apoptosis and its regulation (TUNEL assay, p53, bcl-2, bax), components of antibody-dependent cell mediated cytotoxicity (lymphocytic infiltrate, NK cells, macrophages), angiogenesis (VEGF and microvessel density), HER-2 levels and its phosphorylation status, and breast cell differentiation into a milk-producing phenotype (expression of casein and milk lipids). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR DETERMINANTS OF DRUG SENSITIVITY Principal Investigator & Institution: Hait, William N.; Director; Medicine; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 088545635 Timing: Fiscal Year 2002; Project Start 12-JUL-1999; Project End 30-APR-2004 Summary: The treatment of cancer patients with chemotherapy is often empirical. Even the most active drugs produce meaningful responses in the minority of patients. As a result, many patients are exposed to and suffer the side effects of toxic medications without reaping the benefits. For example, taxanes, such as paclitaxel and docetaxel, and vinca alkaloids, such as vinorelbine, and vinblastine, are amongst the most active drugs in the treatment of common malignancies including breast, lung, and prostate. Yet, less than 50 percent of patients respond to these individual agents. Despite this, clinicians have no way of predicting who will respond and who will not. Mutations in p53 occur in approximately 50 percent of human cancers. Recent studies indicate that p53 mutations affect the sensitivity to cancer chemotherapeutic drugs. In studying the mechanism(s) underlying this observation, we found that increased expression of microtubule associated protein 4 (MAP4), which occurs when p53 is transcriptionally silent, is associated with increased sensitivity to paclitaxel and decreased sensitivity to vinca alkaloids. Using murine fibroblasts transfected with MAP4, we demonstrated that these changes in drug sensitivity were reproduced by overexpression of the MAP4 protein. MAP4 overexpression resulted in alterations in drug-induced apoptosis and cell-cycle arrest. Immunofluorescent staining of the microtubule network revealed that
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cells with increased MAP4 protein expression contained greater polymerized microtubules and bound more fluoresceinated paclitaxel than controls. Since MAP4 catalyzes and stabilizes the polymerization of microtubules, overexpression of this gene provides a credible mechanism to explain the sensitivity to microtubule-active drugs in the presence of mutant p53. Therefore, we propose to study the implications of these observations by analyzing the effects of p53 function on MAP4 overexpression and drug sensitivity in human cancer cell lines and following wild type p53 induction by DNA damage. We will capitalize on our findings to design more rationale uses of antimitotic drugs in combination with DNA damaging agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OSTEOCLASTOGENESIS AS TARGET FOR PROSTATE CANCER OSSEOUS MATASTASES THERAPY Principal Investigator & Institution: Keller, Evan T.; Associate Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2008 Summary: Prostate cancer skeletal metastases are considered osteoblastic; however, histopathological examination usually reveals underlying osteoclastic activity. A key molecule required for induction of osteoclastic activity is receptor activator of NFkB ligand (RANKL). We have determined that prostate cancer cells express increasing levels of RANKL and induce osteoclastogenesis as they progress to bone metastases. Furthermore, in a murine model, we have demonstrated the ability to inhibit establishment of prostate cancer in bone by blocking RANKL-induced osteoclastic activity. Thus, our hypothesis is that RANKL contributes to the development of prostate cancer skeletal metastases, which we will test in the following specific aims: Aim 1. Identify the mechanisms through which RANKL expression is regulated in prostate cancer cells. To understand why RANKL mRNA expression is increased in prostate cancer skeletal metastases, we will characterize the RANKL gene promoter in vitro and in vivo and determine cis-acting sites and trans-acting factors that induce RANKL expression in skeletal metastases. Aim 2. Determine if RANKL is required for the establishment and progression of prostate caneer skeletal metastases in vivo. We will inject prostate cancer tumors into human bone implanted in SCID mice and administer inhibitors of RANKL (i.e., soluble RANK or anti-RANKL antibody) at the time of tumor injection or after tumors become established. We will determine establishment/progression of tumors and expression of bone remodeling markers in the mice. Aim 3. Investigate the effect of docetaxel and estramustine (DE), and a bisphosphonate (Zometa(R)) (Z) on systemic markers of bone remodeling and RANKL expression in bone metastases in men with prostate cancer bone metastases. Men with scan positive bone metastases will be treated with one cycle of Z or DE. This will be followed by two additional cycles of ZED together. Bone markers and indices of prostate cancer response/progression (PSA/bone scans) will be measured at various timepoints. Pre- and post-treatment biopsies of bone metastases in selected patients will be evaluated for RANKL and OPG protein expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOKINETIC TRIAL OF WEEKLY DOCETAXEL IN SOLID TUMOR Principal Investigator & Institution: Rowinsky, Eric K.; Director of Clinical Research; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229
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Timing: Fiscal Year 2002 Summary: Docetaxel, a semisynthetic member of the taxoid family, promotes and stablilizes microtubules and thus inhibits cellular replications. In addition to evaluating the pharmacokinetics of the study drug, the protocol proposes to determine baseline alpha-acid glycoprotein levels and CYP3A4 activity and evaluate whether these levels are predictive for interpatient differences in toxicity and pharmacokinetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGY OF ANTICANCER DRUGS IN ADVANCED AGE Principal Investigator & Institution: Lenz, Heinz Josef.; Associate Professor; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 31-AUG-2004 Summary: Despite the fact that the most rapidly growing segment of the community is the population aged 70 years and older, which is also characterized by the highest overall incidence of cancer, little is known about the detailed pharmacology of cytotoxic agents in this population group. This reflects previous political imperatives, and the conservatism of patients or the medical profession, causing older aged patients to be markedly under-represented in clinical trials. This proposal, from the Women and Special Populations, Genitourinary, Breast and Gastrointestinal Committees of the Southwest Oncology Group, represents the first step in the development of a new paradigm for assessing (a) the feasibility of accrual; (b)the efficacy, toxicity and pharmacology of cytotoxic compounds among patients aged 70 years and older; (c) the feasibility of using standardized self-report measures of comorbidity and functional status in the context of multicenter clinical trials for elderly patients with cancer; (d) at a preliminary level, patterns of expression of key metabolic enzymes in the metabolism of, and resistance to, cytotoxic agents. Fully ambulatory patients in this age group, with metastatic breast cancer, bladder cancer or colorectal malignancy (three of the most common malignancies in this age group) will be treated in a series of standard Phase II trials with docetaxel, gemcitabine-paclitaxel, and uracil-ftorafur [UFT], respectively. The eligibility criteria will be simplified as much as possible to encourage facility of recruitment. In this initial study, elderly patients who are medically fit, apart from the presence of cancer, will be selected, to allow pharmacological and clinical assessment of anticancer therapy that is not confounded by life-threatening undercurrent disease. For each tumor type, 60 cases will be treated. In addition to standard Phase II assessment of efficacy and toxicity, patient-completed questionnaires; will be used as a tool for the assessment of comorbidity and will be used to assess whether the elderly are able successfully to complete such questionnaires, and to identify the extent of previously undiagnosed undercurrent medical disorders, depression, and the level of functional status. Pharmacokinetic measurements will be obtained to establish AUC, half 1ives and clearance values in this elderly population. In addition, we will measure gene expression of deoxycytidine kinase and deaminase (assessing the metabolism of gemcitabine), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) (reflecting metabolism and resistance of flucropyrimidines), and mutations of betatubulin (a potential mechanism of resistance to the taxanes) to study the feasibility of assessing age-related genomic regulation of cytotoxic drug metabolism in Phase Il-III clinical trials. A smaller comparison group of patients aged less than 60 years (with the same cancers) will be treated identically to provide pharmacokinetic data and to validate our pharmacokinetic assays against the published literature. This will allow our pharmacokinetic data from the elderly to be set into context. Comparisons between the elderly populations and the limited younger cohorts will not be possible due to the
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limited case numbers appropriate for the Phase II design of each trial, but the feasibility of data acquisition will be tested and exploration of any obvious correlations between pharmacokinetic characteristics versus efficacy/toxicity will be attempted, but will only be hypothesis-generating in intent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE I/II TRIAL OF AMIFOSTINE, HIGH DOSE CISPLATIN, AND DOCETAXEL IN NSCLC Principal Investigator & Institution: Schiller, Joan H.; Professor; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VEGFR INHIBITOR COMBINED WITH CHEMOTHERAPY FOR NSCLC Principal Investigator & Institution: Folkman, Judah Judah.; Director; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 30-JUN-2008 Summary: New effective therapeutic approaches are needed for NSCLC. Antiangiogenic agents have recently emerged as a class of promising drugs. We hypothesize that simultaneously targeting both the tumor and its vascular supply using combinations of conventional chemotherapy and antiangiogenic agents will be more effective than either approach alone. Previously, we and others have demonstrated that conventional chemotherapeutic agents can act synergistically with angiogenesis inhibitors and may themselves have antiangiogenic activity--even against drug-resistant tumors--when administered on low dose, frequent schedules (metronomic dosing). The optimal means for combining chemotherapeutic agents and antiangiogenic therapy is not yet known. Studies have thus far been hampered by a lack of validated surrogate markers and appropriate animal models to test combinations before moving to human trials. In this project, we propose to investigate the combination of cytotoxic agents with angiogenesis inhibitors in both animal models and in patients with lung cancer. In the first aim, we will systematically assess combinations of taxanes and VEGFR inhibitors using murine models of NSCLC, and determine whether metronomic taxane dosing is more effective than conventional taxane dosing against sensitive and drug-resistant tumors. In the second aim, we will investigate the use of VEGFR inhibitors for different stages of lung cancer progression using a newly developed transgenic murine model. In the third aim, we will investigate the use of circulating endothelial cells and other potential surrogate markers for antiangiogenic activity and VEGFR inhibition. Finally, in the fourth aim, we will test a combination of ZD6474, a VEGFR antagonist, with docetaxel in a Phase II study of patients with NSCLC. In subsequent years, information from these clinical and preclinical studies will be integrated to create and test new combinations in future human trials. We believe that this coordinated, multifaceted approach moving between murine models and human trials will provide a more rational basis for the use of angiogenesis inhibitors in combination with chemotherapeutics for NSCLC and other cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VITAMIN D IN PROSTATE CANCER: TUMOR VASCULATURE EFFECTS Principal Investigator & Institution: Trump, Donald L.; Professor; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): We have demonstrated that the most active vitamin D moiety 1,25 dihydroxycholecalciferol (calcitriol) has significant antiproliferative activity in vivo and in vitro. Calcitriol induces G0/G1 arrest, modulates p27/p21, induces apoptosis and enhances the antitumor activity of cisplatin, carboplatin, paclitaxel and docetaxel. In vitro and in vivo, dexamethasone (dex) potentiates calcitriol-mediated antitumor activity and vitamin D receptor (VDR) ligand binding in vitro and in vivo and enhances VDR protein expression. Calcitriol/dex also suppress activated mitogen-activated protein kinase (MAPK), Ert 1/2) activity and phosphorylated Akt (P-Akt). In a phase II clinical trial of hormone refractory prostate cancer with high dose oral calcitriol and dex, we observed a 50 percent reduction in serum prostate specific antigen (PSA) in 28 percent of patients with no hypercalcemia; modulation of VDR and other potential markers of calcitriol activity in peripheral blood monocytes. We have preliminary data indicating that calcitriol and dex induces apoptosis, modulates cell cycle, decreases P-Erk 1/2 and P-Ark and significantly upregulated VDR expression of tumor-derived endothelial cells (TDEC) as compared to endothelial cells isolated from normal tissues (aortic). These studies suggest that the mechanism(s) of calcitriol/dex antitumor activity may involve effects on intratumor vasculature. We propose to examine this hypothesis by the following Specific Aims: 1) to determine the mechanisms involved in calcitriol/dex effects in TDEC isolated from prostate tumors as compared to normal by examining: a) effects on apoptosis and cell cycle; b) effects on invasiveness, motility, and angiogenesis; and c) whether activities require calcitriol binding to the VDR; 2) To determine the prostate tumor models the role of TDEC in calcitriol/dex antitumor effects by determining: a) effects on the vasculature within the tumor; b) effects on TDEC isolated from animals treated with calcitriol; and c) whether a relationship exists between modulation of effects on TDEC and antitumor effects and 3) To evaluate oral calcitriol (12mg QDx3) and/or dex (4mg QDx4) administered weekly x 4 to patients with localized prostate cancer immediately prior to prostatectomy to determine: a) effects on tumor endothelial cells; b) effects of cell cycle status, apoptosis markers and prostatic intraepithelial neoplasia (PIN) and c) prostate specific antigen (PSA) response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “docetaxel” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for docetaxel in the PubMed Central database: •
Interactions between docetaxel (Taxotere) and Plasmodium falciparum-infected erythrocytes. by Schrevel J, Sinou V, Grellier P, Frappier F, Guenard D, Potier P.; 1994 Aug 30; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44628
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.6 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 use. 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 docetaxel, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “docetaxel” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for docetaxel (hyperlinks lead to article summaries): •
Bio-analysis of docetaxel and hydroxylated metabolites in human plasma by highperformance liquid chromatography and automated solid-phase extraction. Author(s): Rosing H, Lustig V, Koopman FP, ten Bokkel Huinink WW, Beijnen JH. Source: J Chromatogr B Biomed Sci Appl. 1997 August 15; 696(1): 89-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9300913
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Capecitabine and docetaxel in advanced breast cancer: analyses of a phase III comparative trial. Author(s): O'Shaughnessy J. Source: Oncology (Huntingt). 2002 October; 16(10 Suppl 12): 17-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435175
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The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 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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Combined anti-microtubule therapy: a phase II study of weekly docetaxel plus estramustine in patients with metastatic breast cancer. Author(s): Soule SE, Miller KD, Porcu P, Ansari R, Fata F, McClean JW, Zon R, Sledge GW, Einhorn LH. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 October; 13(10): 1612-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377650
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Early response of prostate carcinoma xenografts to docetaxel chemotherapy monitored with diffusion MRI. Author(s): Jennings D, Hatton BN, Guo J, Galons JP, Trouard TP, Raghunand N, Marshall J, Gillies RJ. Source: Neoplasia (New York, N.Y.). 2002 May-June; 4(3): 255-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988845
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Effects of docetaxel on pain due to metastatic androgen-independent prostate cancer. Author(s): Beer TM, Bubalo JS. Source: Curr Urol Rep. 2002 June; 3(3): 232-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084194
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Enhanced oral bioavailability of docetaxel by coadministration of cyclosporine: quantitation and role of P-glycoprotein. Author(s): Chiou WL, Wu TC, Ma C, Jeong HY. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 April 1; 20(7): 1951-2; Author Reply 1952. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11919259
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Epirubicin/docetaxel regimen in progressive breast cancer-a phase II study. Author(s): Salminen E, Korpela J, Varpula M, Asola R, Varjo P, Pyrhonen S, Mali P, Hinkka S, Ekholm E. Source: Anti-Cancer Drugs. 2002 October; 13(9): 925-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394255
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Exisulind in combination with docetaxel inhibits growth and metastasis of human lung cancer and prolongs survival in athymic nude rats with orthotopic lung tumors. Author(s): Chan DC, Earle KA, Zhao TL, Helfrich B, Zeng C, Baron A, Whitehead CM, Piazza G, Pamukcu R, Thompson WJ, Alila H, Nelson P, Bunn PA Jr. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 March; 8(3): 904-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895925
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Expanding horizons: an update on the use of docetaxel in non-small cell lung, ovarian, and breast cancers. Author(s): Hortobagyi GN, Kris MG. Source: Seminars in Oncology. 2002 June; 29(3 Suppl 12): 1-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12170444
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Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. Author(s): Goh BC, Lee SC, Wang LZ, Fan L, Guo JY, Lamba J, Schuetz E, Lim R, Lim HL, Ong AB, Lee HS. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 September 1; 20(17): 3683-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12202670
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Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients. Author(s): Alexandre J, Bleuzen P, Bonneterre J, Sutherland W, Misset JL, Guastalla J, Viens P, Faivre S, Chahine A, Spielman M, Bensmaine A, Marty M, Mahjoubi M, Cvitkovic E. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 February; 18(3): 562-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10653871
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Fatal respiratory failure associated with treatment of prostate cancer using docetaxel and estramustine. Author(s): Morris MJ, Santamauro J, Shia J, Schwartz L, Vander Els N, Kelly K, Scher H. Source: Urology. 2002 December; 60(6): 1111. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475686
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First line combination chemotherapy with docetaxel and vinorelbine in advanced breast cancer. A phase II study. Author(s): Pectasides D, Dimopoulos MA, Aravantinos G, Kalophonos HP, Papacostas P, Briasoulis E, Cogas E, Papadimitriou C, Skarlos D, Kosmidis P, Fountzilas G. Source: Anticancer Res. 2001 September-October; 21(5): 3575-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11848526
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First-line chemotherapy with docetaxel for unresectable or metastatic carcinoma of the biliary tract. A multicentre phase II study. Author(s): Papakostas P, Kouroussis C, Androulakis N, Samelis G, Aravantinos G, Kalbakis K, Sarra E, Souglakos J, Kakolyris S, Georgoulias V. Source: European Journal of Cancer (Oxford, England : 1990). 2001 October; 37(15): 18338. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576836
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First-line treatment of advanced nonsmall cell lung carcinoma with docetaxel and vinorelbine. Author(s): Kourousis C, Androulakis N, Kakolyris S, Souglakos J, Maltezakis G, Metaxaris G, Chalkiadakis G, Samonis G, Vlachonikolis J, Georgoulias V. Source: Cancer. 1998 November 15; 83(10): 2083-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9827712
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First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: a multicenter phase II study. Author(s): Georgoulias V, Androulakis N, Dimopoulos AM, Kourousis C, Kakolyris S, Papadakis E, Apostolopoulou F, Papadimitriou C, Vossos A, Agelidou M, Heras P, Tzannes S, Vlachonicolis J, Mavromanolakis E, Hatzidaki D. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1998 March; 9(3): 331-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9602269
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Fixed erythrodysaesthesia plaque due to intravenous injection of docetaxel. Author(s): Chu CY, Yang CH, Yang CY, Hsiao GH, Chiu HC. Source: The British Journal of Dermatology. 2000 April; 142(4): 808-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10792238
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Front-line treatment of advanced breast cancer with docetaxel and epirubicin: a multicenter phase II study. Author(s): Mavroudis D, Alexopoulos A, Ziras N, Malamos N, Kouroussis C, Kakolyris S, Agelaki S, Kalbakis K, Tsavaris N, Potamianou A, Rigatos G, Georgoulias V. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2000 October; 11(10): 1249-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106112
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Frontline treatment of advanced gastric cancer with docetaxel and granulocyte colonystimulating factor (G-CSF): a phase II trial. Author(s): Mavroudis D, Kourousis C, Androulakis N, Kalbakis K, Agelaki S, Kakolyris S, Souglakos J, Sarra E, Vardakis N, Hatzidaki D, Sarmonis G, Georgoulias V. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2000 August; 23(4): 341-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10955859
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Front-line treatment of advanced non-small-cell lung cancer with docetaxel and gemcitabine: a multicenter phase II trial. Author(s): Georgoulias V, Kouroussis C, Androulakis N, Kakolyris S, Dimopoulos MA, Papadakis E, Bouros D, Apostolopoulou F, Papadimitriou C, Agelidou A, Hatzakis K, Kalbakis K, Kotsakis A, Vardakis N, Vlachonicolis J. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 March; 17(3): 914-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10071284
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Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: a multicenter dose-escalation study. The Greek Breast Cancer Cooperative Group (GBCCG). Author(s): Kouroussis C, Xydakis E, Potamianou A, Giannakakis T, Kakolyris S, Agelaki S, Sara E, Malamos N, Alexopoulos A, Mavroudis D, Samonis G, Papadouris S, Georgoulias V, Panagos G. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1999 May; 10(5): 547-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10416004
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Future perspectives of docetaxel (Taxotere) in front-line therapy. Author(s): Piccart MJ, Di Leo A. Source: Seminars in Oncology. 1997 August; 24(4 Suppl 10): S10-27-S10-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9275004
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Gastrointestinal pneumatosis after docetaxel chemotherapy. Author(s): Candelaria M, Bourlon-Cuellar R, Zubieta JL, Noel-Ettiene LM, SanchezSanchez JM. Source: Journal of Clinical Gastroenterology. 2002 April; 34(4): 444-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907358
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Gastrointestinal toxicity associated with weekly docetaxel treatment. Author(s): Stemmler HJ, Kenngotte S, Diepolder H, Heinemann V. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 June; 13(6): 978-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12123345
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Gemcitabine and docetaxel as second-line chemotherapy for patients with nonsmall cell lung carcinoma who fail prior paclitaxel plus platinum-based regimens. Author(s): Kosmas C, Tsavaris N, Vadiaka M, Stavroyianni N, Koutras A, Malamos N, Onyenadum A, Rokana S, Polyzos A, Kalofonos HP. Source: Cancer. 2001 December 1; 92(11): 2902-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753965
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Gemcitabine and docetaxel every 2 weeks in advanced non-small cell lung cancer: a phase II study of the Gruppo Oncologico Italia Meridionale. Author(s): Galetta D, Gebbia V, Giotta F, Durini E, Romito S, Borsellino N, Cazzato C, Pezzella G, Colucci G. Source: Lung Cancer (Amsterdam, Netherlands). 2002 October; 38(1): 79-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12367797
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Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. Author(s): Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 June 15; 20(12): 2824-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065559
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Gemcitabine-based therapy in pancreas cancer: gemcitabine-docetaxel and other novel combinations. Author(s): Jacobs AD. Source: Cancer. 2002 August 15; 95(4 Suppl): 923-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12209672
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Hepatic biotransformation of docetaxel (Taxotere) in vitro: involvement of the CYP3A subfamily in humans. Author(s): Marre F, Sanderink GJ, de Sousa G, Gaillard C, Martinet M, Rahmani R. Source: Cancer Research. 1996 March 15; 56(6): 1296-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8640817
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High incidence of central nervous system involvement in patients with breast cancer treated with epirubicin and docetaxel. Author(s): Abali H, Celik I. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 December; 25(6): 632-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12478016
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High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Author(s): Crivellari D, Pagani O, Veronesi A, Lombardi D, Nole F, Thurlimann B, Hess D, Borner M, Bauer J, Martinelli G, Graffeo R, Sessa C, Goldhirsch A; International Breast Cancer Study Group. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2001 March; 12(3): 353-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11332148
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High-dose epirubicin plus docetaxel at standard dose with lenograstim support as first-line therapy in advanced breast cancer. Author(s): Milla-Santos A, Milla L, Rallo L, Solano V. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2001 April; 24(2): 138-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11319287
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Hypersensitivity reaction (HSR) to docetaxel after a previous HSR to paclitaxel. Author(s): Denman JP, Gilbar PJ, Abdi EA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 June 1; 20(11): 2760-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12039945
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Hypertrophic osteoarthropathy associated with docetaxel treatment. Author(s): Tas F, Aydiner A, Tenekeci N, Karadeniz A, Sakar B, Topuz E. Source: Clin Oncol (R Coll Radiol). 2001; 13(2): 145-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11373880
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Identification of the highest dose of docetaxel associable with active doses of epirubicin. Results from a dose-finding study in advanced breast cancer patients. Author(s): Venturini M, Michelotti A, Papaldo P, Del Mastro L, Bergaglio M, Lionetto R, Lunardi G, Sguotti C, Frevola L, Donati S, Rosso R, Cognetti F. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2001 August; 12(8): 1097-106. Erratum In: Ann Oncol 2001 October; 12(10): 1498. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583191
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Improved survival in advanced breast cancer with docetaxel and capecitabine in combination: biological synergy or an artefact of trial design? Author(s): Wright TL, Twelves CJ. Source: European Journal of Cancer (Oxford, England : 1990). 2002 October; 38(15): 195760. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376198
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In vitro comparative evaluation of trastuzumab (Herceptin) combined with paclitaxel (Taxol) or docetaxel (Taxotere) in HER2-expressing human breast cancer cell lines. Author(s): Merlin JL, Barberi-Heyob M, Bachmann N. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 November; 13(11): 1743-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12419746
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Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel (Taxotere): association with impaired repositioning of the microtubule organizing center. Author(s): Hotchkiss KA, Ashton AW, Mahmood R, Russell RG, Sparano JA, Schwartz EL. Source: Molecular Cancer Therapeutics. 2002 November; 1(13): 1191-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479700
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Inhibition of growth and metastasis of orthotopic human prostate cancer in athymic mice by combination therapy with pegylated interferon-alpha-2b and docetaxel. Author(s): Huang SF, Kim SJ, Lee AT, Karashima T, Bucana C, Kedar D, Sweeney P, Mian B, Fan D, Shepherd D, Fidler IJ, Dinney CP, Killion JJ. Source: Cancer Research. 2002 October 15; 62(20): 5720-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12384530
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Japanese experience with second-line chemotherapy with low-dose (60 mg/M2) docetaxel in patients with advanced non-small-cell lung cancer. Author(s): Mukohara T, Takeda K, Miyazaki M, Takifuji N, Terakawa K, Negoro S. Source: Cancer Chemotherapy and Pharmacology. 2001 November; 48(5): 356-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11761452
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Lack of CNS penetration of docetaxel in a patient with leptomeningeal carcinomatosis. Author(s): Herrington JD, Di Nunno L, Rinehart JJ. Source: The Annals of Pharmacotherapy. 1998 May; 32(5): 611-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9606487
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Lhermitte's sign following chemotherapy with docetaxel. Author(s): van den Bent MJ, Hilkens PH, Sillevis Smitt PA, van Raaij-van den Aarssen VJ, Bontenbal M, Verweij J. Source: Neurology. 1998 February; 50(2): 563-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9484402
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Life-threatening hypersensitivity pneumonitis induced by docetaxel (taxotere). Author(s): Wang GS, Yang KY, Perng RP. Source: British Journal of Cancer. 2001 November 2; 85(9): 1247-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720456
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Liquid chromatographic analysis and preliminary pharmacokinetics of methotrexate in cancer patients co-treated with docetaxel. Author(s): Sparreboom A, Loos WJ, Nooter K, Stoter G, Verweij J. Source: J Chromatogr B Biomed Sci Appl. 1999 November 26; 735(1): 111-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10630896
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Local erythematous dermatitis after intravenous docetaxel. Author(s): Hirai K, Ishiko O, Nakajima S, Kanaoka Y, Nakamura Y, Oiso N, Ishii M, Ogita S. Source: Gynecologic and Obstetric Investigation. 2002; 53(2): 118-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961387
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Low systemic exposure of oral docetaxel in mice resulting from extensive first-pass metabolism is boosted by ritonavir. Author(s): Bardelmeijer HA, Ouwehand M, Buckle T, Huisman MT, Schellens JH, Beijnen JH, van Tellingen O. Source: Cancer Research. 2002 November 1; 62(21): 6158-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12414642
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Malignant pleural mesothelioma: a phase II trial with docetaxel. Author(s): Vorobiof DA, Rapoport BL, Chasen MR, Abratt RP, Cronje N, Fourie L, McMichael G, Hacking D. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 March; 13(3): 412-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996472
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Meeting highlights 38th annual meeting of the American Society of Clinical Oncology. Advances in adjuvant chemotherapy for management of breast cancer: the emerging role of docetaxel. Author(s): Street JC, Taguchi T. Source: Gan to Kagaku Ryoho. 2002 September; 29(9): 1689-92. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12355960
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Mesenteric venous thrombosis attributed to docetaxel. Author(s): Feenstra J, Vermeer RJ, Stricker BH. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2000 August; 23(4): 353-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10955862
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Metastatic breast cancer in pregnancy: first case of chemotherapy with docetaxel. Author(s): De Santis M, Lucchese A, De Carolis S, Ferrazani S, Caruso A. Source: European Journal of Cancer Care. 2000 December; 9(4): 235-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11829371
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Metastatic breast cancer with resistance to both anthracycline and docetaxel successfully treated with weekly paclitaxel. Author(s): Ishitobi M, Shin E, Kikkawa N. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2001 February; 6(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11706529
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Metastatic eccrine porocarcinoma: response to docetaxel (Taxotere) chemotherapy. Author(s): Plunkett TA, Hanby AM, Miles DW, Rubens RD. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2001 March; 12(3): 411-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11332156
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Mobilization of hematopoietic progenitor cells with a combination of docetaxel, adriamycin, 5-fluorouracil and filgrastim in breast cancer patients. Author(s): Perez-Calvo J, Fernandez-Hidalgo O, Subira ML, Martin-Algarra S, Salgado E, Brugarolas A. Source: Haematologica. 2001 January; 86(1): 100-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11146579
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Mobilization of peripheral blood stem cells in high-risk breast cancer patients using G-CSF after standard dose docetaxel. Author(s): Fleming DR, Goldsmith J, Goldsmith GH, Stevens DA, Herzig RH. Source: Journal of Hematotherapy & Stem Cell Research. 2000 December; 9(6): 855-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11177597
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Modulation of docetaxel-induced apoptosis and cell cycle arrest by all- trans retinoic acid in prostate cancer cells. Author(s): Nehme A, Varadarajan P, Sellakumar G, Gerhold M, Niedner H, Zhang Q, Lin X, Christen RD. Source: British Journal of Cancer. 2001 June 1; 84(11): 1571-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11384110
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Monotherapy with paclitaxel as third-line chemotherapy against anthracyclinepretreated and docetaxel-refractory metastatic breast cancer. Author(s): Kinoshita J, Haga S, Shimizu T, Imamura H, Watanabe O, Nagumo H, Utada Y, Okabe T, Kimura K, Hirano A, Kajiwara T. Source: Breast Cancer. 2002; 9(2): 166-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12016397
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Monthly docetaxel and weekly gemcitabine in metastatic breast cancer: a phase II trial. Author(s): Laufman LR, Spiridonidis CH, Pritchard J, Roach R, Zangmeister J, Larrimer N, Moore T, Segal M, Jones J, Patel T, Gutterman L, Carman L, Colborn D, Kuebler JP. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2001 September; 12(9): 1259-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11697837
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MS-209, a quinoline-type reversal agent, potentiates antitumor efficacy of docetaxel in multidrug-resistant solid tumor xenograft models. Author(s): Naito M, Matsuba Y, Sato S, Hirata H, Tsuruo T. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 February; 8(2): 582-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11839680
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Multicenter phase I-II trial of docetaxel, cisplatin, and fluorouracil induction chemotherapy for patients with locally advanced squamous cell cancer of the head and neck. Author(s): Posner MR, Glisson B, Frenette G, Al-Sarraf M, Colevas AD, Norris CM, Seroskie JD, Shin DM, Olivares R, Garay CA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 February 15; 19(4): 1096-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11181674
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Nail changes due to docetaxel. Author(s): Pavithran K, Doval DC. Source: The British Journal of Dermatology. 2002 April; 146(4): 709-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966714
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Nail changes secondary to docetaxel (Taxotere). Author(s): Correia O, Azevedo C, Pinto Ferreira E, Braga Cruz F, Polonia J. Source: Dermatology (Basel, Switzerland). 1999; 198(3): 288-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393455
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Nanomolar range docetaxel treatment sensitizes MCF-7 cells to chemotherapy induced apoptosis, induces G2M arrest and phosphorylates bcl-2. Author(s): Berchem GJ, Bosseler M, Mine N, Avalosse B. Source: Anticancer Res. 1999 January-February; 19(1A): 535-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10226594
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Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. Author(s): Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 March 15; 20(6): 1456-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11896092
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Neoadjuvant chemotherapy with docetaxel in non--small cell lung cancer. Author(s): Mattson K. Source: Seminars in Oncology. 2001 June; 28(3 Suppl 9): 33-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441413
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Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: a preliminary report. Author(s): Oh WK, George DJ, Kaufman DS, Moss K, Smith MR, Richie JP, Kantoff PW. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 15): 40-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685727
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Neoadjuvant docetaxel in breast cancer: 3-year survival results from the Aberdeen trial. Author(s): Heys SD, Hutcheon AW, Sarkar TK, Ogston KN, Miller ID, Payne S, Smith I, Walker LG, Eremin O; Aberdeen Breast Group. Source: Clinical Breast Cancer. 2002 October; 3 Suppl 2: S69-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435290
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Neo-adjuvant therapy with dose-dense docetaxel plus short-term filgrastim rescue for locally advanced breast cancer. Author(s): Paciucci PA, Raptis G, Bleiweiss I, Weltz C, Lehrer D, Gurry R. Source: Anti-Cancer Drugs. 2002 September; 13(8): 791-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394262
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Neoadjuvant treatment with docetaxel and the effects of irradiation for human ovarian adenocarcinoma and cervical squamous cell carcinoma in vitro. Author(s): Araki S, Miyagi Y, Kawanishi K, Yamamoto J, Hongo A, Kodama J, Yoshinouchi M, Kudo T. Source: Acta Medica Okayama. 2002 February; 56(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11873939
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New approaches in the adjuvant and neoadjuvant therapy of non-small cell lung cancer, including docetaxel (Taxotere) combinations. Author(s): Rosell R. Source: Seminars in Oncology. 1999 June; 26(3 Suppl 11): 32-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10458209
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Nonanthracycline containing docetaxel-based combinations in metastatic breast cancer. Author(s): Crown J. Source: The Oncologist. 2001; 6 Suppl 3: 17-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346680
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Nonneutropenic febrile episodes associated with docetaxel-based chemotherapy in patients with solid tumors. Author(s): Souglakos J, Kotsakis A, Kouroussis C, Kakolyris S, Mavroudis D, Kalbakis K, Agelaki S, Vlachonikolis J, Georgoulias V, Samonis G. Source: Cancer. 2002 September 15; 95(6): 1326-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12216102
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Non-platinum based combination chemotherapy: phase I and II trials of docetaxel plus gemcitabine, vinorelbine, or irinotecan. Author(s): Rigas JR. Source: Seminars in Oncology. 2001 June; 28(3 Suppl 9): 15-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441410
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Novel compounds in the therapy of breast cancer: opportunities for integration with docetaxel. Author(s): Tolcher AW. Source: The Oncologist. 2001; 6 Suppl 3: 40-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346685
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Onycholysis in patients treated with docetaxel. Author(s): Obermair A, Binder M, Barrada M, Bancher-Todesca D, Asseryanis E, Kubista E. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1998 February; 9(2): 230-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9553674
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Optimal sampling strategies for bayesian estimation of docetaxel (Taxotere) clearance. Author(s): Baille P, Bruno R, Schellens JH, Webster LK, Millward M, Verweij J, Montay G. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1997 September; 3(9): 1535-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9815840
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Optimal use of docetaxel (Taxotere): maximizing its potential. Author(s): Burris HA. Source: Anti-Cancer Drugs. 1996 August; 7 Suppl 2: 25-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8862707
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Orally active docetaxel analogue: synthesis of 10-deoxy-10-C-morpholinoethyl docetaxel analogues. Author(s): Iimura S, Uoto K, Ohsuki S, Chiba J, Yoshino T, Iwahana M, Jimbo T, Terasawa H, Soga T. Source: Bioorganic & Medicinal Chemistry Letters. 2001 February 12; 11(3): 407-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11212122
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Outpatient therapy with gemcitabine and docetaxel for gallbladder, biliary, and cholangio-carcinomas. Author(s): Kuhn R, Hribaschek A, Eichelmann K, Rudolph S, Fahlke J, Ridwelski K. Source: Investigational New Drugs. 2002 August; 20(3): 351-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201499
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Overexpression of Bcl-2 regulates sodium butyrate- and/or docetaxel-induced apoptosis in human bladder cancer cells both in vitro and in vivo. Author(s): Miyake H, Hara S, Arakawa S, Kamidono S, Hara I. Source: International Journal of Cancer. Journal International Du Cancer. 2001 July 1; 93(1): 26-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11391617
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Overview of docetaxel (Taxotere) in the treatment of non-small cell lung cancer. Author(s): Fossella FV. Source: Seminars in Oncology. 1999 June; 26(3 Suppl 11): 4-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10458203
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Overview of docetaxel (Taxotere)/cisplatin combination in non-small cell lung cancer. Author(s): Le Chevalier T, Berille J, Zalcberg JR, Millward MJ, Monnier A, Douillard JY, McKeage MJ, James R, Soulas F, Loret C, Bougon N, Bizzari JP. Source: Seminars in Oncology. 1999 June; 26(3 Suppl 11): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10458205
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Phase 3 randomized trial evaluating second-line hormonal therapy versus docetaxelestramustine combination chemotherapy on progression-free survival in asymptomatic patients with a rising prostate-specific antigen level after hormonal therapy for prostate cancer: an Eastern Cooperative Oncology Group (E1899), Intergroup/Clinical Trials Support Unit study. Author(s): Walczak JR, Carducci MA; Eastern Cooperative Oncology Group E1899. Source: Urology. 2003 December 29; 62 Suppl 1: 141-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747052
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Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Author(s): Katori H, Tsukuda M, Mochimatu I, Ishitoya J, Kawai S, Mikami Y, Matsuda H, Tanigaki Y, Horiuchi C, Ikeda Y, Taguchi T, Ono M, Yoshida T, Hirose S, Sakuma Y, Yamamoto K. Source: British Journal of Cancer. 2004 January 26; 90(2): 348-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14735175
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Quality of life in patients with metastatic breast cancer receiving either docetaxel or sequential methotrexate and 5-fluorouracil. A multicentre randomised phase III trial by the Scandinavian breast group. Author(s): Hakamies-Blomqvist L, Luoma M, Sjostrom J, Pluzanska A, Sjodin M, Mouridsen H, Ostenstad B, Mjaaland I, Ottosson-Lonn S, Bergh J, Malmstrom P, Blomqvist C. Source: European Journal of Cancer (Oxford, England : 1990). 2000 July; 36(11): 1411-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10899655
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Radiation recall dermatitis from docetaxel. Author(s): Piroth MD, Krempien R, Wannenmacher M, Zierhut D. Source: Onkologie. 2002 October; 25(5): 438-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12415198
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Randomized phase II trial of either fluorouracil, parenteral hydroxyurea, interferonalpha-2a, and filgrastim or doxorubicin/docetaxel in patients with advanced gastric cancer with quality-of-life assessment: eastern cooperative oncology group study E6296. Author(s): Wadler S, Brain C, Catalano P, Einzig AI, Cella D, Benson AB 3rd. Source: Cancer Journal (Sudbury, Mass.). 2002 May-June; 8(3): 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074329
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Rapid high-performance liquid chromatographic determination of docetaxel (Taxotere) in plasma using liquid-liquid extraction. Author(s): Ciccolini J, Catalin J, Blachon MF, Durand A. Source: J Chromatogr B Biomed Sci Appl. 2001 August 15; 759(2): 299-306. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499483
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Responses to docetaxel plus vinorelbine in metastatic breast cancer patients failing high-dose chemotherapy. Author(s): Andres R, Mayordomo JI, Isla D, Marti JL, Escudero P, Filipovich E, Saenz A, Alvarez I, Polo E, Tres A. Source: British Journal of Cancer. 2002 March 18; 86(6): 1017-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11953839
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Retrospective analysis of administration of a combination of docetaxel and carboplatin for advanced non-small cell lung cancer. Author(s): Bando H, Miyata J, Sano T, Sumitomo M. Source: Anticancer Res. 2001 May-June; 21(3C): 2107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11501833
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Review of two phase II randomized trials of single-agent docetaxel in previously treated advanced non--small cell lung cancer. Author(s): Lynch TJ Jr. Source: Seminars in Oncology. 2001 June; 28(3 Suppl 9): 5-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11444253
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Salvage chemotherapy with the gemcitabine/docetaxel combination in non-small cell lung cancer: an overview of recent phase II studies. Author(s): Kosmas C, Tsavaris N, Kalofonos HP. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 June; 8(6): Pi58-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12070450
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Second-line treatment with docetaxel after failure of a platinum-based chemotherapy in squamous-cell head and neck cancer. Author(s): Numico G, Merlano M. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 February; 13(2): 331-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11886014
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Sensitive liquid chromatography-mass spectrometry assay for quantitation of docetaxel and paclitaxel in human plasma. Author(s): Parise RA, Ramanathan RK, Zamboni WC, Egorin MJ. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 January 5; 783(1): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12450543
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Sequential or alternating administration of docetaxel (Taxotere) combined with FEC in metastatic breast cancer: a randomised phase II trial. Author(s): Spielmann M, Tubiana-Hulin M, Namer M, Mansouri H, Bougnoux P, Tubiana-Mathieu N, Lotz V, Eymard JC. Source: British Journal of Cancer. 2002 March 4; 86(5): 692-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11875727
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Severe interstitial pneumonitis associated with docetaxel administration. Author(s): Read WL, Mortimer JE, Picus J. Source: Cancer. 2002 February 1; 94(3): 847-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857321
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Squamous syringometaplasia associated with docetaxel. Author(s): Karam A, Metges JP, Labat JP, Leroy JP, Guillet G. Source: The British Journal of Dermatology. 2002 March; 146(3): 524-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952559
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Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. Author(s): O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 June 15; 20(12): 2812-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065558
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Survival of docetaxel-resistant prostate cancer cells in vitro depends on phenotype alterations and continuity of drug exposure. Author(s): Makarovskiy AN, Siryaporn E, Hixson DC, Akerley W. Source: Cellular and Molecular Life Sciences : Cmls. 2002 July; 59(7): 1198-211. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222966
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Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. Author(s): Bafaloukos D, Gogas H, Georgoulias V, Briassoulis E, Fountzilas G, Samantas E, Kalofonos Ch, Skarlos D, Karabelis A, Kosmidis P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 January 15; 20(2): 420-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11786569
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The current status of docetaxel for metastatic breast cancer. Author(s): Esteva FJ. Source: Oncology (Huntingt). 2002 June; 16(6 Suppl 6): 17-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12108894
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The current status of docetaxel in solid tumors. An M. D. Anderson Cancer Center Review. Author(s): Hong WK. Source: Oncology (Huntingt). 2002 June; 16(6 Suppl 6): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12108903
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The European experience with docetaxel in the treatment of early-stage breast cancer. Author(s): Di Leo A. Source: Clinical Breast Cancer. 2002 October; 3 Suppl 2: S59-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435289
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The impact of drug administration sequence and pharmacokinetic interaction in a phase I study of the combination of docetaxel and gemcitabine in patients with advanced solid tumors. Author(s): Dumez H, Louwerens M, Pawinsky A, Planting AS, de Jonge MJ, Van Oosterom AT, Highley M, Guetens G, Mantel M, de Boeck G, de Bruijn E, Verweij J. Source: Anti-Cancer Drugs. 2002 July; 13(6): 583-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172503
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The integration of docetaxel into first-line chemotherapy for ovarian cancer. Author(s): Kaye SB; Scottish Gynaecological Cancer Trials Group. Source: International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. 2001; 11 Suppl 1: 31-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11489000
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The role of docetaxel in the management of squamous cell cancer of the head and neck. Author(s): Glisson BS. Source: Oncology (Huntingt). 2002 June; 16(6 Suppl 6): 83-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12108901
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Treatment of advanced breast cancer with docetaxel and gemcitabine with and without human granulocyte colony-stimulating factor. Author(s): Kornek GV, Haider K, Kwasny W, Raderer M, Schull B, Payrits T, Depisch D, Kovats E, Lang F, Scheithauer W. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 May; 8(5): 1051-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006518
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Treatment side effects. Case 2. Toxic, epidermal, necrolysis-like reaction associated with docetaxel chemotherapy. Author(s): Dourakis SP, Sevastianos VA, Alexopoulou A, Deutsch M, Stavrianeas N. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 July 1; 20(13): 3030-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12089234
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Two special types of breast cancer presenting as progressive disease after neoadjuvant chemotherapy with docetaxel plus doxorubicin. Author(s): Takahashi T, Akashi-Tanaka S, Fukutomi T, Watanabe T, Katsumata N, Miyakawa K, Hasegawa T, Tsuda H. Source: Breast Cancer. 2001; 8(3): 234-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668246
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Unexpected toxicity after low-dose docetaxel treatment of a cancer patient with clinically latent HCV-positive hepatic cirrhosis. Author(s): Koukourakis MI, Kapsoritakis A, Maltezos E, Potamiano S, Mouzas I, Kouroumalis H. Source: Anticancer Res. 2002 July-August; 22(4): 2491-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12174950
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Use of docetaxel (Taxotere) in patients with paclitaxel (Taxol) hypersensitivity. Author(s): Moon C, Verschraegen CF, Bevers M, Freedman R, Kudelka AP, Kavanagh JJ. Source: Anti-Cancer Drugs. 2000 August; 11(7): 565-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11036959
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Variation in the kinetics of caspase-3 activation, Bcl-2 phosphorylation and apoptotic morphology in unselected human ovarian cancer cell lines as a response to docetaxel. Author(s): Kolfschoten GM, Hulscher TM, Duyndam MC, Pinedo HM, Boven E. Source: Biochemical Pharmacology. 2002 February 15; 63(4): 733-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992642
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CHAPTER 2. NUTRITION AND DOCETAXEL Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and docetaxel.
Finding Nutrition Studies on Docetaxel 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; 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]). 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.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: 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. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “docetaxel” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 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.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “docetaxel” (or a synonym): •
A phase II trial of docetaxel for peripheral blood stem cell mobilization for patients with breast cancer and ovarian cancer. Author(s): The University of Chicago, Division of Hematology/Oncology, Chicago, IL, USA. Source: Laport, G G Fleming, G F Waggoner, S Zimmerman, T M Grinblatt, D L Williams, S F Bone-Marrow-Transplant. 2001 April; 27(7): 677-81 0268-3369
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A sequence-dependent combination of docetaxel and vinorelbine: pharmacokinetic interactions. Author(s): Dipartimento di Scienza e Tecnologia del Farmaco, Scuola di Specializzazione in Farmacia Ospedaliera, Turin, Italy.
[email protected] Source: Cattel, L Recalenda, V Airoldi, M Tagini, V Arpicco, S Brusa, P Bumma, C Farmaco. 2001 October; 56(10): 779-84 0014-827X
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Anticancer activity of docetaxel in murine salivary gland carcinoma. Author(s): Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
[email protected] Source: Piechocki, Marie P Lonardo, Fulvio Ensley, John F Nguyen, Tam Kim, Harold Yoo, George H Clin-Cancer-Res. 2002 Mar; 8(3): 870-7 1078-0432
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Cellular sensitivity determinants to docetaxel in human gastrointestinal cancers. Author(s): Department of Biochemistry and Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. Source: Park, Ji Seon Yamamoto, Wataru Sekikawa, Takashi Matsukawa, Masaaki Okamoto, Ryo Sasaki, Masao Ukon, Kei Tanimoto, Keiji Kumazaki, Tsutomu Nishiyama, Masahiko Int-J-Oncol. 2002 February; 20(2): 333-8 1019-6439
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Combination of docetaxel and doxorubicin as first-line chemotherapy in metastatic breast cancer. Author(s): Hacettepe University Institute of Oncology, Department of Medical Oncology, Ankara, Turkey. Source: Baltali, E Ozisik, Y Guler, N Firat, D Altundag, K Tumori. 2001 Jan-February; 87(1): 18-9 0300-8916
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Combined effects of docetaxel and fluoropyrimidines on tumor growth and expression of interleukin-6 and thymidine phosphorylase in breast cancer xenografts. Author(s): Department of Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, Japan. Source: Yamamoto, S Kurebayashi, J Kurosumi, M Kunisue, H Otsuki, T Tanaka, K Sonoo, H Cancer-Chemother-Pharmacol. 2001 October; 48(4): 283-8 0344-5704
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Combined modality treatment of oral and oropharyngeal cancer including neoadjuvant intraarterial cisplatin and radical surgery followed by concurrent radiation and chemotherapy with weekly docetaxel - three year results of a pilot study. Author(s): Department of Maxillofacial Plastic Surgery, Johann Wolfgang GoetheUniversity Frankfurt Medical School, Frankfurt am Main, Germany.
[email protected] Source: Kovacs, A F Schiemann, M Turowski, B J-Craniomaxillofac-Surg. 2002 April; 30(2): 112-20 1010-5182
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Concurrent administration of Docetaxel and Stealth liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection. Author(s): Tumour and Angiogenesis Research Group, PO Box 12, Democritus University of Thrace, Alexandroupolis 68100, Greece.
[email protected] Source: Koukourakis, M I Romanidis, K Froudarakis, M Kyrgias, G Koukourakis, G V Retalis, G Bahlitzanakis, N Br-J-Cancer. 2002 August 12; 87(4): 385-92 0007-0920
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Cooperative inhibitory effect of novel mixed backbone oligonucleotide targeting protein kinase A in combination with docetaxel and anti-epidermal growth factorreceptor antibody on human breast cancer cell growth. Author(s): Cattedra di Oncologia Medica, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Universita Federico II, Napoli, Italy. Source: Tortora, G Caputo, R Pomatico, G Pepe, S Bianco, A R Agrawal, S Mendelsohn, J Ciardiello, F Clin-Cancer-Res. 1999 April; 5(4): 875-81 1078-0432
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Determination of the docetaxel vehicle, polysorbate 80, in patient samples by liquid chromatography-tandem mass spectrometry. Author(s): Laboratory of Experimental Chemotherapy and Pharmacology, Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, Groene Hilledijk 301, The Netherlands.
[email protected] Source: Sparreboom, Alex Zhao, Ming Brahmer, Julie R Verweij, Jaap Baker, Sharyn D JChromatogr-B-Analyt-Technol-Biomed-Life-Sci. 2002 June 25; 773(2): 183-90 1570-0232
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Dose-escalation study of docetaxel in combination with mitoxantrone as first-line treatment in patients with metastatic breast cancer. Author(s): Department of Medical Oncology, School of Medicine, University of Crete, Heraklion, Greece. Source: Kouroussis, C Androulakis, N Kakolyris, S Souglakos, J Kotsakis, T Mavroudis, D Katsogridakis, K Vardakis, N Hatzidaki, D Samonis, G Vlachonikolis, J Georgoulias, V J-Clin-Oncol. 1999 March; 17(3): 862-9 0732-183X
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Dose-finding phase I study of simultaneous weekly infusion with doxorubicin and docetaxel in patients with advanced breast cancer. Author(s): Department of Medical Oncology, Cancer Institute Hospital, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 KamiIkebukuro, Toshima-ku, Tokyo 170-8455, Japan.
[email protected] Source: Ito, Y Aiba, K Horikoshi, N Saotome, T Irie, T Sugiyama, K Nakane, M Hashimoto, D Yoshida, N Mizunuma, N Takahashi, S Tanigawara, Y Int-J-Clin-Oncol. 2001 October; 6(5): 242-7 1341-9625
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Drug interactions of paclitaxel and docetaxel and their relevance for the design of combination therapy. Author(s): Division of Medical Oncology A, Istituto Nazionale dei Tumori di Milano, Milan, Italy. Source: Vigano, L Locatelli, A Grasselli, G Gianni, L Invest-New-Drugs. 2001 May; 19(2): 179-96 0167-6997
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Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer. Author(s): Department of Medical Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario, Canada.
[email protected]
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Source: Leighl, Natasha B Shepherd, Frances A Kwong, Rita Burkes, Ronald L Feld, Ronald Goodwin, Pamela J J-Clin-Oncol. 2002 March 1; 20(5): 1344-52 0732-183X •
Influence of amifostine on the toxicity and pharmacokinetics of docetaxel in metastatic breast cancer patients: a pilot study. Author(s): Laboratoire d'Oncopharmacologie, Unite de chimiotherapie,Service de Medecine Interne et Laboratoire d'Investigation Clinique et d'Oncologie Experimentale HJ Tagnon, Institut Jules Bordet, 1000, Brussels, Belgium. Source: Freyer, Gilles Hennebert, Philippe Awada, Ahmad Gil, Thierry Kerger, Joseph Selleslags, Jean Brassinne, Christiane Piccart, Martine de Valeriola, Dominique ClinCancer-Res. 2002 January; 8(1): 95-102 1078-0432
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Mobilization of peripheral blood stem cells with docetaxel and cyclophosphamide (CY) in patients with metastatic breast cancer: a randomized trial of 3 vs 4 g/m2 of CY. Author(s): Clinical Research Division of Response Oncology, Inc, Memphis, TN, USA. Source: Weaver, C H Schwartzberg, L S Zhen, B Franco, C Moore, M Smith, R White, L Van Amburg, A Hazelton, B Buckner, C D Bone-Marrow-Transplant. 1999 Mar; 23(5): 421-5 0268-3369
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Paclitaxel and docetaxel enhance the metabolism of doxorubicin to toxic species in human myocardium. Author(s): Department of Drug Sciences, G. D'Annunzio University School of Pharmacy, 66013 Chieti, Italy.
[email protected] Source: Minotti, G Saponiero, A Licata, S Menna, P Calafiore, A M Teodori, G Gianni, L Clin-Cancer-Res. 2001 June; 7(6): 1511-5 1078-0432
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Perspectives and opportunities: Docetaxel in the current and future treatment of nonsmall cell lung cancer. Author(s): Department of Medicine, Medical University of South Carolina, Charleston 29425, USA. Source: Green, Mark R Semin-Oncol. 2002 June; 29(3 Suppl 12): 17-21 0093-7754
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Pharmacobiologically based scheduling of capecitabine and docetaxel results in antitumor activity in resistant human malignancies. Author(s): Department of Medicine, Ohio State University College of Medicine and Public Health, Columbus, OH 43210-1240, USA. Source: Nadella, Padma Shapiro, Charles Otterson, Gregory A Hauger, Marsha Erdal, Selnur Kraut, Eric Clinton, Steven Shah, Manisha Stanek, Mike Monk, Paul Villalona Calero, Miguel A J-Clin-Oncol. 2002 June 1; 20(11): 2616-23 0732-183X
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Pharmacokinetic and pharmacodynamic study of the combination of docetaxel and topotecan in patients with solid tumors. Author(s): Program of Molecular Therapeutics and Drug Discovery, University of Pittsburgh Cancer Institute, PA 15213, USA.
[email protected] Source: Zamboni, W C Egorin, M J Van Echo, D A Day, R S Meisenberg, B R Brooks, S E Doyle, L A Nemieboka, N N Dobson, J M Tait, N S Tkaczuk, K H J-Clin-Oncol. 2000 September 15; 18(18): 3288-94 0732-183X
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Phase I and pharmacokinetic study of two sequences of gemcitabine and docetaxel administered weekly to patients with advanced cancer. Author(s): Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA. Source: Bhargava, P Marshall, J L Fried, K Williams, M Lefebvre, P Dahut, W Hanfelt, J Gehan, E Figuera, M Hawkins, M J Rizvi, N A Cancer-Chemother-Pharmacol. 2001 August; 48(2): 95-103 0344-5704
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Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Author(s): Department of Medical Oncology, Cancer Research UK, West of Scotland Clinical Trials Unit, Beatson Oncology Centre, E Block, Western Infirmary, Glasgow, G11 6NT, Scotland, UK.
[email protected] Source: Vasey, P A Roche, H Bisset, D Terret, C Vernillet, L Riva, A Ramazeilles, C Azli, N Kaye, S B Twelves, C J Br-J-Cancer. 2002 November 4; 87(10): 1072-8 0007-0920
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Phase I study of second-line chemotherapy with docetaxel and carboplatin in advanced non-small-cell lung cancer. Author(s): Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
[email protected] Source: Oka, M Fukuda, M Nagashima, S Fukuda, M Kinoshita, A Soda, H Doi, S Narasaki, F Suenaga, M Takatani, H Nakamura, Y Kawabata, S Tsurutani, J Kanda, T Kohno, S Cancer-Chemother-Pharmacol. 2001 December; 48(6): 446-50 0344-5704
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Phase I trial of docetaxel with estramustine in androgen-independent prostate cancer. Author(s): Department of Medicine, Columbia Presbyterian Medical Center, New York, NY 10032, USA.
[email protected] Source: Petrylak, D P Macarthur, R B O'Connor, J Shelton, G Judge, T Balog, J Pfaff, C Bagiella, E HeitJanuary, D Fine, R Zuech, N Sawczuk, I Benson, M Olsson, C A J-ClinOncol. 1999 March; 17(3): 958-67 0732-183X
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Phase I/II trial of weekly epidoxorubicin and docetaxel (wED) in the neoadjuvant and palliative treatment of patients with breast cancer. Author(s): Department of Internal Medicine I/Division of Oncology, University Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Source: Wenzel, C Locker, G J Pluschnig, U Zielinski, C C Rudas, M Oberhuber, G Gnant, M F Taucher, S Jakesz, R Steger, G G Cancer-Chemother-Pharmacol. 2002 August; 50(2): 155-9 0344-5704
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Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer. Author(s): Institut Catala d'Oncologia, Department of Medical Oncology, Avda Gran Via km 2.7, 08907 L'Hospitalet, Barcelona, Spain.
[email protected] Source: Garcia del Muro, X Marcuello, E Guma, J Paz Ares, L Climent, M A Carles, J Parra, M Sanchez Tisaire, J L Maroto, P Germa, J R Br-J-Cancer. 2002 February 1; 86(3): 326-30 0007-0920
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Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer. Author(s): Department of Internal Medicine, Korea University, College of Medicine, Seoul, Korea. Source: Kim, Y H Kim, J S Choi, Y H In, K H Park, H S Hong, D S Jeong, T J Lee, Y Y Nam, E Lee, S N Lee, K S Kim, H K Int-J-Clin-Oncol. 2002 April; 7(2): 114-9 1341-9625
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Phase II study of weekly docetaxel and trastuzumab for patients with HER-2overexpressing metastatic breast cancer. Author(s): Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
[email protected] Source: Esteva, Francisco J Valero, Vicente Booser, Daniel Guerra, Laura T Murray, James L Pusztai, Lajos Cristofanilli, Massimo Arun, Banu Esmaeli, Bita Fritsche, Herbert A Sneige, Nour Smith, Terry L Hortobagyi, Gabriel N J-Clin-Oncol. 2002 April 1; 20(7): 1800-8 0732-183X
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Phase II Trial of docetaxel and cisplatin combination chemotherapy in patients with squamous cell carcinoma of the head and neck. Author(s): University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
[email protected] Source: Glisson, Bonnie S Murphy, Barbara A Frenette, Gary Khuri, Fadlo R Forastiere, Arlene A J-Clin-Oncol. 2002 March 15; 20(6): 1593-9 0732-183X
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Preclinical and clinical studies of docetaxel and exisulind in the treatment of human lung cancer. Author(s): University of Colorado Cancer Center, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Source: Bunn, Paul A Jr Chan, Daniel C Earle, Keith Zhao, Tom L M Helfrich, Barbara Kelly, Karen Piazza, Gary Whitehead, Clark M Pamukcu, Rifat Thompson, William Alila, Hector Semin-Oncol. 2002 February; 29(1 Suppl 4): 87-94 0093-7754
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Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracyclinecontaining chemotherapy. 304 Study Group. Author(s): Cross-Cancer Institute, Edmonton, Alberta, Canada.
[email protected] Source: Nabholtz, J M Senn, H J Bezwoda, W R Melnychuk, D Deschenes, L Douma, J Vandenberg, T A Rapoport, B Rosso, R Trillet Lenoir, V Drbal, J Molino, A Nortier, J W Richel, D J Nagykalnai, T Siedlecki, P Wilking, N Genot, J Y Hupperets, P S Pannuti, F Skarlos, D Tomiak, E M Murawsky, M Alakl, M Aapro, M et al. J-Clin-Oncol. 1999 May; 17(5): 1413-24 0732-183X
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Review of docetaxel and doxorubicin-based combinations in the management of breast cancer: from metastatic to adjuvant setting. Author(s): Northern Alberta Breast Cancer Program, Cross Cancer Institute, Edmonton, Canada. Source: Nabholtz, J M Tonkin, K Smylie, M Mackey, J Janowska Wieczorek, A SeminOncol. 1999 February; 26(1 Suppl 3): 10-6 0093-7754
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Scleroderma in association with the use of docetaxel (taxotere) for breast cancer. Author(s): Department of Rheumatology, Westmead Hospital, Australia. Source: Hassett, G Harnett, P Manolios, N Clin-Exp-Rheumatol. 2001 Mar-April; 19(2): 197-200 0392-856X
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Synergistic inhibition of human lung cancer cell growth by adenovirus-mediated wild-type p53 gene transfer in combination with docetaxel and radiation therapeutics in vitro and in vivo. Author(s): Division of Surgery, Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. Source: Nishizaki, M Meyn, R E Levy, L B Atkinson, E N White, R A Roth, J A Ji, L ClinCancer-Res. 2001 September; 7(9): 2887-97 1078-0432
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The effect of pretreatment with docetaxel (taxotere; RP 56976) on irradiated subcutaneous MA 16/C murine tumors. Author(s): Academic Hospital, Free University of Brussels, Dept. of Radiotherapy, Belgium.
[email protected] Source: Distelmans, W Storme, G J-Exp-Clin-Cancer-Res. 1999 June; 18(2): 167-72 03929078
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The efficacy of chemotherapy with docetaxel and paclitaxel in anthracycline-resistant breast cancer (Review). Author(s): Centre Antoine Lacassagne, 06056 Nice, France.
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Source: Pivot, X AsMarch, L Hortobagyi, G N Int-J-Oncol. 1999 August; 15(2): 381-6 1019-6439 •
The use of docetaxel (Taxotere) in patients with advanced non-small cell lung cancer previously treated with platinum-containing chemotherapy regimens. Author(s): Department of Thoracic/Head & Neck Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030-4009, USA. Source: Fossella, F V Rigas, J Semin-Oncol. 1999 June; 26(3 Suppl 11): 9-12 0093-7754
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Weekly high-dose calcitriol and docetaxel in advanced prostate cancer. Author(s): Department of Medicine, Oregon Health Sciences University and the Portland Veterans Affairs Medical Center, Portland, OR 97201, USA. Source: Beer, T M Hough, K M Garzotto, M Lowe, B A Henner, W D Semin-Oncol. 2001 August; 28(4 Suppl 15): 49-55 0093-7754
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.healthnotes.com/
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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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WebMDHealth: 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 docetaxel; 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: •
Vitamins Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Zinc Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND DOCETAXEL Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to docetaxel. At the conclusion of this chapter, we will provide additional sources.
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 facilitate research for articles that specifically relate to docetaxel and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “docetaxel” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to docetaxel: •
A case of docetaxel-induced erythrodysesthesia. Author(s): Katoh M, Kadota M, Nishimura Y. Source: The Journal of Dermatology. 2004 May; 31(5): 403-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15187308
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A case of metastatic breast cancer with outgrowth of HER2-negative cells after eradication of HER2-positive cells by humanized anti-HER2 monoclonal antibody (trastuzumab) combined with docetaxel. Author(s): Kunitomo K, Inoue S, Ichihara F, Kono K, Fujii H, Matsumoto Y, Ooi A. Source: Human Pathology. 2004 March; 35(3): 379-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017597
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A case of radiation recall mucositis associated with docetaxel. Author(s): Culp LR, Pou AM, Jones DV, Bayouth J, Sanguineti G.
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Source: Head & Neck. 2004 February; 26(2): 197-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762890 •
A dose escalation study of docetaxel and oxaliplatin combination in patients with metastatic breast and non-small cell lung cancer. Author(s): Kouroussis C, Agelaki S, Mavroudis D, Kakolyris S, Androulakis N, Kalbakis K, Souglakos J, Mallas K, Bozionelou V, Pallis A, Adamtziki H, Georgoulias V. Source: Anticancer Res. 2003 January-February; 23(1B): 785-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680184
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A feasibility study on biweekly administration of docetaxel for patients with recurrent ovarian cancer. Author(s): Oishi T, Kigawa J, Fujiwara K, Fujiwara M, Numa F, Aotani E, Katsumata N, Kohno I, Kato H, Terakawa N; Sankai Gynecology Study Group. Source: Gynecologic Oncology. 2003 August; 90(2): 421-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893211
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A multicenter phase II study of cisplatin and docetaxel (Taxotere) in the first-line treatment of advanced ovarian cancer: a GINECO study. Author(s): Dieras V, Guastalla JP, Ferrero JM, Cure H, Weber B, Winckel P, Lortholary A, Mayer F, Paraiso D, Magherini E, Pujade-Lauraine E. Source: Cancer Chemotherapy and Pharmacology. 2004 June; 53(6): 489-95. Epub 2004 February 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767617
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A multicenter phase II study of docetaxel and carboplatin combination as front-line treatment in advanced non-small cell lung cancer. Author(s): Giannakakis T, Kakolyris S, Theodoropoulos E, Kouroussis C, Michailakis E, Papadouris S, Tsitoura M, Kalbakis K, Souglakos J, Agelaki S, Vardakis N, Georgoulias V. Source: Anticancer Res. 2002 November-December; 22(6B): 3743-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552987
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A multicenter phase II study of the combination of gemcitabine and docetaxel in previously treated patients with small cell lung cancer. Author(s): Agelaki S, Veslemes M, Syrigos K, Palamidas F, Polyzos A, Papakotoulas P, Kentepozidis N, Milaki G, Tzanakis N, Kouroussis C, Vamvakas L, Georgoulias V; Hellenic Oncology Research Group. Source: Lung Cancer (Amsterdam, Netherlands). 2004 March; 43(3): 329-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15165092
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A multicenter phase II study of the efficacy and safety of docetaxel plus cisplatin in Asian chemonaive patients with metastatic or locally advanced non-small cell lung cancer.
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Author(s): Ho JC, Tan EH, Leong SS, Wang CH, Sun Y, Li R, Wahid MI, Jusuf A, Liao M, Guan Z, Handoyo P, Huang JS, Chan V, Luna G, Tsang KW, Lam WK; Asian-Pacific Collaborative Group. Source: Respiratory Medicine. 2003 July; 97(7): 796-803. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854629 •
A phase I dose-escalation study of docetaxel with granulocyte colony-stimulating factor support in patients with solid tumours. Author(s): Mitchell PL, Basser R, Chipman M, Grigg A, Cebon J, Davis ID, Zalcberg J, Ng S, Appia F, Green M. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 May; 14(5): 788-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702535
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A phase I study of carboplatin and docetaxel for advanced non-small cell lung cancer using the continual reassessment method. Author(s): Kasahara K, Myo S, Iwasa K, Kimura H, Shirasaki H, Yasuda U, Shibata K, Shintani H, Nishi K, Fujimura M, Nakao S. Source: Japanese Journal of Clinical Oncology. 2002 December; 32(12): 512-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12578899
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A Phase I study of docetaxel plus cyclophosphamide in solid tumors followed by a Phase II study as first-line therapy in metastatic breast cancer. Author(s): Trent JC, Valero V, Booser DJ, Esparza-Guerra LT, Ibrahim N, Rahman Z, Vernillet L, Patel S, David CL, Murray JL, Cristofanilli M, Hortobagyi GN. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 July; 9(7): 2426-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12855614
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A phase I study of gemcitabine and docetaxel for advanced stage solid tumors. Author(s): Poole ME, Bernard SA, Churchel MA, Weissler MC, Calvo B, Cance W, Ollila D, Koruda M, Behrns K, Detterbeck FC. Source: Cancer Investigation. 2003 June; 21(3): 350-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901280
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A phase II study of capecitabine and docetaxel combination chemotherapy in patients with advanced gastric cancer. Author(s): Park YH, Ryoo BY, Choi SJ, Kim HT. Source: British Journal of Cancer. 2004 April 5; 90(7): 1329-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15054450
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A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients.
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Author(s): Ohe Y, Niho S, Kakinuma R, Kubota K, Ohmatsu H, Goto K, Nokihara H, Kunitoh H, Saijo N, Aono H, Watanabe K, Tango M, Yokoyama A, Nishiwaki Y. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2004 January; 15(1): 45-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679118 •
A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status. Author(s): Johnson FM, Garden A, Palmer JL, Kies M, Clayman G, Brumfield B, Khuri FR, Morrison W, Papadimitrakopoulou V, Diaz EM, Glisson BS. Source: Cancer. 2004 March 1; 100(5): 991-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983495
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A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Author(s): Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, Moore DH. Source: Gynecologic Oncology. 2003 February; 88(2): 130-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586591
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A phase II study of docetaxel-irinotecan combination in advanced pancreatic cancer. Author(s): Kurtz JE, Negrier S, Husseini F, Limacher JM, Borel C, Wagner JP, Prevot G, Bergerat JP, Dufour P. Source: Hepatogastroenterology. 2003 March-April; 50(50): 567-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749274
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A phase II study of estramustine, docetaxel, and carboplatin with granulocyte-colonystimulating factor support in patients with hormone-refractory prostate carcinoma: Cancer and Leukemia Group B 99813. Author(s): Oh WK, Halabi S, Kelly WK, Werner C, Godley PA, Vogelzang NJ, Small EJ; Cancer and Leukemia Group B 99813. Source: Cancer. 2003 December 15; 98(12): 2592-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14669278
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A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinoma. Author(s): Gitlitz BJ, Baker C, Chapman Y, Allen HJ, Bosserman LD, Patel R, Sanchez JD, Shapiro RM, Figlin RA. Source: Cancer. 2003 November 1; 98(9): 1863-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14584068
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A phase II study of sequential docetaxel followed by doxorubicin/cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Author(s): Anton A, Hornedo J, Lluch A, Massuti B, Corral M, Colomer R.
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Source: Clinical Breast Cancer. 2003 October; 4(4): 286-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651774 •
A phase II study of three-weekly docetaxel and weekly trastuzumab in HER2overexpressing advanced breast cancer. Author(s): Montemurro F, Choa G, Faggiuolo R, Donadio M, Minischetti M, Durando A, Capaldi A, Vietti-Ramus G, Alabiso O, Aglietta M. Source: Oncology. 2004; 66(1): 38-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15031597
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A phase II study of weekly docetaxel plus capecitabine for patients with advanced nonsmall cell lung carcinoma. Author(s): Han JY, Lee DH, Kim HY, Hong EK, Yoon SM, Chun JH, Lee HG, Lee SY, Shin EH, Lee JS. Source: Cancer. 2003 November 1; 98(9): 1918-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14584075
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A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia. Author(s): Jatoi A, Tirona MT, Cha SS, Alberts SR, Rowland KM, Morton RF, Nair S, Kardinal CG, Stella PJ, Mailliard JA, Sargen D, Goldberg RM. Source: International Journal of Gastrointestinal Cancer. 2002; 32(2-3): 115-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794247
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A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma. Author(s): Tiersten AD, Nelsen C, Talbot S, Vahdat L, Fine R, Troxel A, Brafman L, Shriberg L, Antman K, Petrylak DP. Source: Cancer. 2003 February 1; 97(3): 537-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548594
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A phase-II study of liposomal doxorubicin and docetaxel in patients with advanced pancreatic cancer. Author(s): Syrigos KN, Michalaki B, Alevyzaki F, Machairas A, Mandrekas D, Kindilidis K, Karatzas G. Source: Anticancer Res. 2002 November-December; 22(6B): 3583-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552960
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A randomized phase II study of alternating and sequential regimens of docetaxel and doxorubicin as first-line chemotherapy for metastatic breast cancer. Author(s): Paridaens R, Van Aelst F, Georgoulias V, Samonnig H, Cocquyt V, Zielinski C, Hausmaninger H, Willemse P, Boudraa Y, Wildiers J, Ramazeilles C, Azli N.
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Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 March; 14(3): 433-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598350 •
A randomized phase II study of combination, alternating and sequential regimens of doxorubicin and docetaxel as first-line chemotherapy for women with metastatic breast cancer. Author(s): Cresta S, Grasselli G, Mansutti M, Martoni A, Lelli G, Capri G, Buzzi F, Cuna GR, Jirillo A, Terzoli E, Frevola L, Tarenzi E, Sguotti C, Azli N, Murawsky M, Gianni L. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2004 March; 15(3): 433-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998845
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A rapid and sensitive liquid chromatography/tandem mass spectrometry method for determination of docetaxel in human plasma. Author(s): Wang LZ, Goh BC, Grigg ME, Lee SC, Khoo YM, Lee HS. Source: Rapid Communications in Mass Spectrometry : Rcm. 2003; 17(14): 1548-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845579
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A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-smallcell lung cancer. Author(s): Massarelli E, Andre F, Liu DD, Lee JJ, Wolf M, Fandi A, Ochs J, Le Chevalier T, Fossella F, Herbst RS. Source: Lung Cancer (Amsterdam, Netherlands). 2003 January; 39(1): 55-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499095
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A third-generation matrix metalloproteinase (MMP) inhibitor (ONO-4817) combined with docetaxel suppresses progression of lung micrometastasis of MMP-expressing tumor cells in nude mice. Author(s): Yamamoto A, Yano S, Shiraga M, Ogawa H, Goto H, Miki T, Zhang H, Sone S. Source: International Journal of Cancer. Journal International Du Cancer. 2003 March 1; 103(6): 822-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516105
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Activity of docetaxel in paclitaxel-resistant ovarian cancer cells. Author(s): Sato S, Kigawa J, Kanamori Y, Itamochi H, Oishi T, Shimada M, Iba T, Naniwa J, Uegaki K, Terakawa N. Source: Cancer Chemotherapy and Pharmacology. 2004 March; 53(3): 247-52. Epub 2003 November 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610615
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Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts. Author(s): Oudard S, Legrier ME, Boye K, Bras-Goncalves R, De Pinieux G, De Cremoux P, Poupon MF. Source: The Journal of Urology. 2003 May; 169(5): 1729-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12686819
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Additive effects of radiation and docetaxel on murine SCCVII tumors in vivo: special reference to changes in the cell cycle. Author(s): Suzuki M, Nakamatsu K, Kanamori S, Masunaga S, Nishimura Y. Source: Radiation Research. 2003 June; 159(6): 799-804. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751963
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Alpha-1-acid glycoprotein as an independent predictor for treatment effects and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel. Author(s): Bruno R, Olivares R, Berille J, Chaikin P, Vivier N, Hammershaimb L, Rhodes GR, Rigas JR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 March; 9(3): 1077-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12631610
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Alternating doublets: establishing the optimal multifractionated dosing schedule to administer docetaxel, cisplatin, gemcitabine, and vinorelbine in combination. Author(s): Lokich J, Anderson N, Coco F. Source: Cancer Investigation. 2003; 21(6): 830-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14735686
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Amelioration of docetaxel/cisplatin induced polyneuropathy by alpha-lipoic acid. Author(s): Gedlicka C, Kornek GV, Schmid K, Scheithauer W. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 339-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562664
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An overview of current results with the gemcitabine and docetaxel combination as initial and salvage chemotherapy regimen in advanced non-small cell lung cancer. Author(s): Kosmas C, Tsavaris N, Mylonakis N, Kalofonos HP. Source: Critical Reviews in Oncology/Hematology. 2003 March; 45(3): 265-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633839
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Analysis of docetaxel pharmacokinetics in humans with the inclusion of later sampling time-points afforded by the use of a sensitive tandem LCMS assay. Author(s): Gustafson DL, Long ME, Zirrolli JA, Duncan MW, Holden SN, Pierson AS, Eckhardt SG.
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Source: Cancer Chemotherapy and Pharmacology. 2003 August; 52(2): 159-66. Epub 2003 May 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759775 •
Antitumor activity of doxorubicin in combination with docetaxel against human breast cancer xenografts. Author(s): Egawa T, Kubota T, Suto A, Otani Y, Furukawa T, Saikawa Y, Watanabe M, Kumai K, Kitajima M. Source: In Vivo. 2003 January-February; 17(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12655785
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Antitumor activity of irofulven monotherapy and in combination with mitoxantrone or docetaxel against human prostate cancer models. Author(s): Van Laar ES, Weitman S, MacDonald JR, Waters SJ. Source: The Prostate. 2004 April 1; 59(1): 22-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991863
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Antitumor effects of epidermal growth factor receptor antisense oligonucleotides in combination with docetaxel in squamous cell carcinoma of the head and neck. Author(s): Niwa H, Wentzel AL, Li M, Gooding WE, Lui VW, Grandis JR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 October 15; 9(13): 5028-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581378
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Atrial fibrillation during adjuvant chemotherapy with docetaxel: a case report. Author(s): Palma M, Mancuso A, Grifalchi F, Lugini A, Pizzardi N, Cortesi E. Source: Tumori. 2002 November-December; 88(6): 527-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12597151
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Bcl-2 and bax expression in advanced non-small cell lung cancer: lack of correlation with chemotherapy response or survival in patients treated with docetaxel plus vinorelbine. Author(s): Krug LM, Miller VA, Filippa DA, Venkatraman E, Ng KK, Kris MG. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 139-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581565
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Biweekly administration of low-dose docetaxel in hormone-resistant prostate cancer: pilot study of an effective subtoxic therapy. Author(s): Karavasilis V, Briasoulis E, Siarabi O, Pavlidis N. Source: Clin Prostate Cancer. 2003 June; 2(1): 46-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046684
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Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer. Author(s): Yoshioka T, Sakata Y, Terashima M, Sekikawa K, Gamoh M, Mitachi Y, Saitoh S, Kanamaru R. Source: Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2003; 6(3): 153-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520528
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Biweekly docetaxel and gemcitabine as neoadjuvant chemotherapy in stage II and III breast cancer patients: preliminary results of a phase II and pharmacogenomic study. Author(s): Estevez LG, Sanchez-Rovira P, Domine M, Leon A, Calvo I, Jaen A, Casado V, Rubio G, Daz M, Miro C, Lobo F. Source: Seminars in Oncology. 2004 April; 31(2 Suppl 5): 31-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15199530
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Biweekly docetaxel and vinorelbine in anthracycline-resistant metastatic breast cancer: a multicenter phase II study. Author(s): Gomez-Bernal A, Cruz JJ, Garcia-Palomo A, Arizcun A, Pujol E, Diz P, Martin G, Fonseca E, Sanchez P, Rodriguez C, del Barco E, Lopez Y. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 April; 26(2): 127-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714881
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Biweekly docetaxel-irinotecan with filgrastim support in pretreated breast and nonsmall-cell lung cancer patients. A phase I study. Author(s): Frasci G, Comella P, Thomas R, Di Bonito M, Lapenta L, Capasso I, Botti G, Vallone P, De Rosa V, D'Aiuto G, Comella G. Source: Cancer Chemotherapy and Pharmacology. 2004 January; 53(1): 25-32. Epub 2003 September 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513281
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Blockage of the lacrimal drainage apparatus as a side effect of docetaxel therapy. Author(s): Esmaeli B, Hidaji L, Adinin RB, Faustina M, Coats C, Arbuckle R, Rivera E, Valero V, Tu SM, Ahmadi MA. Source: Cancer. 2003 August 1; 98(3): 504-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879466
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Cancer and Leukemia Group B (CALGB) 90203: a randomized phase 3 study of radical prostatectomy alone versus estramustine and docetaxel before radical prostatectomy for patients with high-risk localized disease. Author(s): Eastham JA, Kelly WK, Grossfeld GD, Small EJ; Cancer and Leukemia Group B.
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Source: Urology. 2003 December 29; 62 Suppl 1: 55-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747042 •
Capecitabine in combination with docetaxel and epirubicin in patients with previously untreated, advanced breast carcinoma. Author(s): Venturini M, Durando A, Garrone O, Colozza MA, Contu A, Stevani I, Genta F, Bighin C, Lambiase A, Del Mastro L. Source: Cancer. 2003 March 1; 97(5): 1174-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12599222
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Carboplatin and docetaxel in advanced non-small-cell lung cancer: results of a multicenter phase II study. Author(s): Ramalingam S, Dobbs TW, Einzig AI, Wojtowicz-Praga S, Cascino M, Bonomi P, Belani CP. Source: Cancer Chemotherapy and Pharmacology. 2004 May; 53(5): 439-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15132135
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Cervical adenocarcinoma treated with docetaxel and carboplatin. Author(s): Oguri H, Maeda N, Fukaya T. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 November; 83(2): 209-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550601
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Cholestatic jaundice and pseudomembranous colitis following combination therapy with doxorubicin and docetaxel. Author(s): Sundar S, Chan SY. Source: Anti-Cancer Drugs. 2003 April; 14(4): 327-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679738
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Clinical data and pharmacokinetics of a docetaxel-vinorelbine combination in anthracycline resistant/ relapsed metastatic breast cancer. Author(s): Airoldi M, Cattel L, Pedani F, Marchionatti S, Tagini V, Bumma C, Recalenda V. Source: Acta Oncologica (Stockholm, Sweden). 2003; 42(3): 186-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12852694
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Clinical pharmacokinetics of unbound docetaxel: role of polysorbate 80 and serum proteins. Author(s): Loos WJ, Baker SD, Verweij J, Boonstra JG, Sparreboom A. Source: Clinical Pharmacology and Therapeutics. 2003 October; 74(4): 364-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534523
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Combination chemotherapy with docetaxel and irinotecan in metastatic malignant melanoma. Author(s): Tas F, Camlica H, Kurul S, Aydiner A, Topuz E. Source: Clin Oncol (R Coll Radiol). 2003 May; 15(3): 132-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801051
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Combination docetaxel and platelet-derived growth factor receptor inhibition with imatinib mesylate in prostate cancer. Author(s): Mathew P, Fidler IJ, Logothetis CJ. Source: Seminars in Oncology. 2004 April; 31(2 Suppl 6): 24-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15176001
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Combination of docetaxel, epirubicin and vinorelbine administered every 2 weeks as first-line therapy in patients with metastatic breast cancer: a dose-finding study. Author(s): Esteban E, Modollel A, Gonzalez de Sande L, Palacio I, Muniz I, Fernandez Y, Corral N, Fra J, Sala M, Vieitez JM, Estrada E, Lacave AJ; Grupo Oncologico del Norte de Espana. Source: Breast Cancer Research and Treatment. 2003 August; 80(3): 257-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14503798
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Combination second-line chemotherapy with gemcitabine and docetaxel for recurrent non-small-cell lung cancer after platinum-containing chemotherapy: a phase I/II trial. Author(s): Niho S, Kubota K, Goto K, Ohmatsu H, Matsumoto T, Kakinuma R, Nishiwaki Y. Source: Cancer Chemotherapy and Pharmacology. 2003 July; 52(1): 19-24. Epub 2003 April 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12712259
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Combination treatment with weekly docetaxel and gemcitabine for advanced nonsmall-cell lung cancer in elderly patients and patients with poor performance status: results of a Minnie Pearl Cancer Research Network phase II trial. Author(s): Hainsworth JD, Erland JB, Barton JH, Thompson DS, Stagg MP, Bradof JE, Twele TW, Greco EA; Minnie Pearl Cancer Research Network. Source: Clinical Lung Cancer. 2003 July; 5(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596701
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Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine. Author(s): Pei J, Zhang C, Gokhale PC, Rahman A, Dritschilo A, Ahmad I, Kasid UN. Source: Anti-Cancer Drugs. 2004 March; 15(3): 243-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15014358
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Combined effects of docetaxel and angiostatin gene therapy in prostate tumor model. Author(s): Galaup A, Opolon P, Bouquet C, Li H, Opolon D, Bissery MC, Tursz T, Perricaudet M, Griscelli F. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2003 June; 7(6): 731-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12788646
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Comparison of antiangiogenic activities using paclitaxel (taxol) and docetaxel (taxotere). Author(s): Grant DS, Williams TL, Zahaczewsky M, Dicker AP. Source: International Journal of Cancer. Journal International Du Cancer. 2003 March 10; 104(1): 121-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12532428
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Concomitant weekly docetaxel, cisplatin and radiation therapy in locally advanced non-small cell lung cancer: a dose finding study. Author(s): Mudad R, Ramsey M, Kovitz K, Curiel TJ, Hartz R, Nedzi LL, Weiner RS, Zakris EL. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581570
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Concurrent two-dimensional radiotherapy and weekly docetaxel in the treatment of stage III non-small cell lung cancer: a good local response but no good survival due to radiation pneumonitis. Author(s): Onishi H, Kuriyama K, Yamaguchi M, Komiyama T, Tanaka S, Araki T, Nishikawa K, Ishihara H. Source: Lung Cancer (Amsterdam, Netherlands). 2003 April; 40(1): 79-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660011
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Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-smallcell lung cancer: phase II Southwest Oncology Group Study S9504. Author(s): Gandara DR, Chansky K, Albain KS, Leigh BR, Gaspar LE, Lara PN Jr, Burris H, Gumerlock P, Kuebler JP, Bearden JD 3rd, Crowley J, Livingston R; Southwest Oncology Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 May 15; 21(10): 2004-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743155
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Current studies with docetaxel in hormone-refractory prostate cancer: selected presentations from the 27th European Society for Medical Oncology Congress, 2002. Author(s): DeGrendele H. Source: Clin Prostate Cancer. 2003 March; 1(4): 212-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040878
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Cystic maculopathy with normal capillary permeability secondary to docetaxel. Author(s): Teitelbaum BA, Tresley DJ. Source: Optometry and Vision Science : Official Publication of the American Academy of Optometry. 2003 April; 80(4): 277-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692483
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Decreased response to paclitaxel versus docetaxel in HER-2/neu transfected human breast cancer cells. Author(s): Witters LM, Santala SM, Engle L, Chinchilli V, Lipton A. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 February; 26(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576925
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Delayed seroma formation secondary to docetaxel. Author(s): Sultan MR, Madhere SM. Source: Annals of Plastic Surgery. 2003 April; 50(4): 429-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671389
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Docetaxel (taxotere) in the treatment of prostate cancer. Author(s): Beer TM, El-Geneidi M, Eilers KM. Source: Expert Review of Anticancer Therapy. 2003 June; 3(3): 261-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820771
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Docetaxel (taxotere) induced subacute cutaneous lupus erythematosus: report of 4 cases. Author(s): Chen M, Crowson AN, Woofter M, Luca MB, Magro CM. Source: The Journal of Rheumatology. 2004 April; 31(4): 818-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15088316
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Docetaxel and carboplatin as first-line chemotherapy in patients with advanced gynecological tumors. A phase I/II trial of the Arbeitsgemeinschaft Gynakologische Onkologie (AGO-OVAR) Ovarian Cancer Study Group. Author(s): Pfisterer J, du Bois A, Wagner U, Quaas J, Blohmer JU, Wallwiener D, Hilpert F; Arbeitsgemeinschaft Gynakologische Onkologie (AGO-OVAR) Ovarian Cancer Study Group. Source: Gynecologic Oncology. 2004 March; 92(3): 949-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984965
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Docetaxel and carboplatin as first-line therapy in advanced non-small cell lung carcinoma: a phase II study. Author(s): Jahanzeb M, Sarna G, Hirsch R, Radice P, Koletsky A, Martinez M, Kruglyak E, Wolin E, Camacho E, Kronish L, Motl S.
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Source: Anticancer Res. 2004 March-April; 24(2C): 1239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15154653 •
Docetaxel and carboplatin combination chemotherapy for recurrent endometrial cancer. Author(s): Obata H, Aoki Y, Watanabe M, Matsushita H, Yahata T, Fujita K, Kurata H, Tanaka K. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 February; 8(1): 53-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601544
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Docetaxel and carboplatin is an active regimen in advanced non-small-cell lung cancer: a phase II study in Caucasian and Asian patients. Author(s): Millward MJ, Boyer MJ, Lehnert M, Clarke S, Rischin D, Goh BC, Wong J, McNeil E, Bishop JF. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 March; 14(3): 449-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598352
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Docetaxel and cisplatin in patients with advanced gastric cancer: results of Japanese phase I/II study. Author(s): Saitoh S, Sakata Y. Source: Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2002; 5 Suppl 1: 23-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772883
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Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. Author(s): Bamias A, Aravantinos G, Deliveliotis C, Bafaloukos D, Kalofonos C, Xiros N, Zervas A, Mitropoulos D, Samantas E, Pectasides D, Papakostas P, Gika D, Kourousis C, Koutras A, Papadimitriou C, Bamias C, Kosmidis P, Dimopoulos MA; Hellenic Cooperative Oncology Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 January 15; 22(2): 220-8. Epub 2003 December 09. Erratum In: J Clin Oncol. 2004 May 1; 22(9): 1771. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665607
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Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. Author(s): Nabholtz JM, Falkson C, Campos D, Szanto J, Martin M, Chan S, Pienkowski T, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A, Pouillart P; TAX 306 Study Group.
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Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 15; 21(6): 968-75. Erratum In: J Clin Oncol. 2003 May 15; 21(10): 2048. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637459 •
Docetaxel and epirubicin supported by granulocyte colony-stimulating factor firstline in advanced breast cancer. Author(s): Polyzos A, Tsavaris N, Kosmas C, Gogas H, Vadiaka M, Markopoulos C, Giannopoulos A, Kalahanis N, Stamatiadis D, Kouraklis G, Karatzas G, Liapis C, Syrigos K. Source: Anticancer Res. 2003 May-June; 23(3C): 2917-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926135
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Docetaxel and gemcitabine combination, as first-line treatment, in patients with extensive disease small-cell lung cancer. A phase II study of the Hellenic Cooperative Oncology Group. Author(s): Skarlos DV, Dimopoulos AM, Kosmidis P, Papakostas P, Pavlidis N, Bacoyiannis C, Kiamouris C, Klouvas G, Gogas H, Fountzilas G, Samantas E; Hellenic Cooperative Oncology Group. Source: Lung Cancer (Amsterdam, Netherlands). 2003 July; 41(1): 107-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826319
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Docetaxel and ketoconazole in advanced hormone-refractory prostate carcinoma: a phase I and pharmacokinetic study. Author(s): Van Veldhuizen PJ, Reed G, Aggarwal A, Baranda J, Zulfiqar M, Williamson S. Source: Cancer. 2003 November 1; 98(9): 1855-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14584067
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Docetaxel and radiotherapy and pancreatic cancer. Author(s): Viret F, Ychou M, Goncalves A, Moutardier V, Magnin V, Braud AC, Dubois JB, Bories E, Gravis G, Camerlo J, Genre D, Maraninchi D, Viens P, Giovannini M. Source: Pancreas. 2003 October; 27(3): 214-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508124
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Docetaxel and vinorelbine in recurrent head and neck cancer: pharmacokinetic and clinical results. Author(s): Airoldi M, Cattel L, Marchionatti S, Recalenda V, Pedani F, Tagini V, Bumma C, Beatrice F, Succo G, Maria Gabriele A. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 August; 26(4): 378-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902890
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Docetaxel and vinorelbine: an effective regimen in recurrent squamous cell esophageal carcinoma. Author(s): Airoldi M, Cortesina G, Giordano C, Pedani F, Bumma C, Gabriele P. Source: Medical Oncology (Northwood, London, England). 2003; 20(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665680
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Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma. Author(s): Vallejo CT, Machiavelli MR, Perez JE, Romero AO, Bologna F, Vicente H, Lacava JA, Ortiz EH, Cubero A, Focaccia G, Suttora G, Scenna M, Boughen JM, Leone BA. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 October; 26(5): 477-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528074
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Docetaxel as neoadjuvant therapy for radically treatable stage III non-small-cell lung cancer: a multinational randomised phase III study. Author(s): Mattson KV, Abratt RP, ten Velde G, Krofta K. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 January; 14(1): 116-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488303
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Docetaxel as salvage therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico Italia Meridionale (G.O.I.M.). Author(s): Giuliani F, Gebbia V, De Vita F, Maiello E, Di Bisceglie M, Catalano G, Gebbia N, Colucci G. Source: Anticancer Res. 2003 September-October; 23(5B): 4219-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666628
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Docetaxel as second-line chemotherapy for advanced non-small cell lung cancer. Author(s): Thongprasert S, Cheewakriangkrai R, Napapan S. Source: J Med Assoc Thai. 2002 December; 85(12): 1296-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12678167
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Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: a multi-institutional phase II trial. Author(s): Tedesco KL, Thor AD, Johnson DH, Shyr Y, Blum KA, Goldstein LJ, Gradishar WJ, Nicholson BP, Merkel DE, Murrey D, Edgerton S, Sledge GW Jr. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 March 15; 22(6): 1071-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15020608
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Docetaxel enhances the therapeutic effect of the angiogenesis inhibitor TNP-470 (AGM-1470) in metastatic human transitional cell carcinoma. Author(s): Inoue K, Chikazawa M, Fukata S, Yoshikawa C, Shuin T. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 February; 9(2): 886-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576464
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Docetaxel in advanced gastric cancer--review of the main clinical trials. Author(s): Di Cosimo S, Ferretti G, Fazio N, Silvestris N, Carlini P, Alimonti A, Gelibter A, Felici A, Papaldo P, Cognetti F. Source: Acta Oncologica (Stockholm, Sweden). 2003; 42(7): 693-700. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14690154
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Docetaxel in non-small cell lung cancer: a review. Author(s): Davies AM, Lara PN Jr, Mack PC, Gandara DR. Source: Expert Opinion on Pharmacotherapy. 2003 April; 4(4): 553-65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667118
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Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck. Author(s): Posner MR, Lefebvre JL. Source: British Journal of Cancer. 2003 January 13; 88(1): 11-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556952
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Docetaxel inhibits SMMC-7721 human hepatocellular carcinoma cells growth and induces apoptosis. Author(s): Geng CX, Zeng ZC, Wang JY. Source: World Journal of Gastroenterology : Wjg. 2003 April; 9(4): 696-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679913
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Docetaxel plus 5-fluorouracil for terminal gastric cancer patients with peritoneal dissemination. Author(s): Eguchi T, Fujii M, Wakabayashi K, Aisaki K, Tsuneda Y, Kochi M, Takayama T. Source: Hepatogastroenterology. 2003 September-October; 50(53): 1735-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571830
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Docetaxel plus epirubicin is a highly active, well-tolerated, first-line chemotherapy for metastatic breast cancer: results of a large, multicentre phase II study. Author(s): Morales S, Lorenzo A, Ramos M, Ballesteros P, Mendez M, Almanza C, Castellanos J, Moreno-Nogueira JA, Casal J, Lizon J, Oltra A, Frau A, Machengs I, Galan A, Belon J, Llorca C.
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Source: Cancer Chemotherapy and Pharmacology. 2004 January; 53(1): 75-81. Epub 2003 October 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557896 •
Docetaxel versus paclitaxel for adjuvant treatment of ovarian cancer: case-control analysis of toxicity. Author(s): Hsu Y, Sood AK, Sorosky JI. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2004 February; 27(1): 14-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14758127
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Docetaxel with concurrent radiotherapy in head and neck cancer. Author(s): Nabell L, Spencer S. Source: Seminars in Oncology. 2003 December; 30(6 Suppl 18): 89-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14727247
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Docetaxel with epirubicin--investigations on cardiac safety. Author(s): Salminen E, Syvanen K, Korpela J, Varpula M, Antila K, Varjo P, Ekholm E. Source: Anti-Cancer Drugs. 2003 January; 14(1): 73-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544261
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Docetaxel, carboplatin and concomitant radiotherapy for unresectable squamous cell carcinoma of the head and neck: pharmacokinetic and clinical data of a phase I-II study. Author(s): Airoldi M, Cattel L, Cortesina G, Giordano C, Pedani F, Recalenda V, Danova M, Gabriele AM, Tagini V, Porta C, Bumma C. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2004 April; 27(2): 155-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057155
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Docetaxel, cisplatin, 5-fluorouracil (TPF)-based induction chemotherapy for head and neck cancer and the case for sequential, combined-modality treatment. Author(s): Haddad R, Tishler RB, Norris CM, Mahadevan A, Busse P, Wirth L, Goguen LA, Sullivan CA, Costello R, Case MA, Posner MR. Source: The Oncologist. 2003; 8(1): 35-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604730
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Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck: the Dana Farber Cancer Institute experience. Author(s): Haddad R, Colevas AD, Tishler R, Busse P, Goguen L, Sullivan C, Norris CM, Lake-Willcutt B, Case MA, Costello R, Posner M.
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Source: Cancer. 2003 January 15; 97(2): 412-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518365 •
Docetaxel: an alternative taxane in ovarian cancer. Author(s): Katsumata N. Source: British Journal of Cancer. 2003 December; 89 Suppl 3: S9-S15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14661041
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Docetaxel: promising and novel combinations in ovarian cancer. Author(s): Maenpaa JU. Source: British Journal of Cancer. 2003 December; 89 Suppl 3: S29-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14661044
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Docetaxel-anthracycline combinations in metastatic breast cancer. Author(s): Nabholtz JM. Source: Breast Cancer Research and Treatment. 2003; 79 Suppl 1: S3-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868800
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Docetaxel-based chemotherapy in the treatment of gastric cancer. Author(s): Roth AD, Ajani J. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003; 14 Suppl 2: Ii41-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810457
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Docetaxel-based combined-modality chemoradiotherapy for locally advanced nonsmall cell lung cancer. Author(s): Scagliotti GV, Turrisi AT 3rd. Source: The Oncologist. 2003; 8(4): 361-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897333
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Docetaxel-ifosfamide combination chemotherapy in patients with metastatic hormone-refractory prostate cancer: a phase I pharmacokinetic study. Author(s): Hervonen P, Jekunen A, Lefebvre P, Kellokumpu-Lehtinen P. Source: Int J Clin Pharmacol Res. 2003; 23(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621067
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Docetaxel-induced histologic changes in the lacrimal sac and the nasal mucosa. Author(s): Esmaeli B, Burnstine MA, Ahmadi MA, Prieto VG. Source: Ophthalmic Plastic and Reconstructive Surgery. 2003 July; 19(4): 305-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878879
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Docetaxel-related skin, nail, and vascular toxicity. Author(s): Leonard GD, Zujewski JA. Source: The Annals of Pharmacotherapy. 2003 January; 37(1): 148. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12564432
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Durable complete remission after weekly docetaxel administration in a patient with mediastinal non-seminomatous germ-cell tumor refractory to cisplatin-based chemotherapy. Author(s): Berruti A, Saini A, Gorzegno G, Tampellini M, Borasio P, Dogliotti L. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 October; 14(10): 1589-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504064
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Effect of cytochrome P450 3A4 inhibition on the pharmacokinetics of docetaxel. Author(s): Engels FK, Ten Tije AJ, Baker SD, Lee CK, Loos WJ, Vulto AG, Verweij J, Sparreboom A. Source: Clinical Pharmacology and Therapeutics. 2004 May; 75(5): 448-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15116057
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Effect of the combination of docetaxel, zoledronic acid, and a COX-2 inhibitor on the growth of human breast cancer cell lines. Author(s): Witters LM, Crispino J, Fraterrigo T, Green J, Lipton A. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 August; 26(4): S92-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902864
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Effective combination chemotherapy with bimonthly docetaxel and cisplatin with or without hematopoietic growth factor support in patients with advanced gastroesophageal cancer. Author(s): Schull B, Kornek GV, Schmid K, Raderer M, Hejna M, Lenauer A, Depisch D, Lang F, Scheithauer W. Source: Oncology. 2003; 65(3): 211-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657594
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Effective weekly docetaxel for recurrent ovarian cancer: A case report. Author(s): Komiyama S, Mizusawa Y, Onouchi M, Takehara K, Suzuki A, Mikami M. Source: International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. 2003 September-October; 13(5): 683-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675355
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Effectiveness of doxifluridine (5'-DFUR)/docetaxel against advanced/recurrent gastric cancer showing resistance to various anticancer drug regimens. Author(s): Sato A, Shimada K, Nakamachi M, Ushio J, Yamamoto W, Kurihara M, Matsukawa M.
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Source: Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2002; 5(4): 233-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12491082 •
Efficacy of intra-arterial infusion therapy using a combination of cisplatin and docetaxel for recurrent head and neck cancers compared with cisplatin alone. Author(s): Yabuuchi H, Kuroiwa T, Tajima T, Tomita K, Ochiai N, Kawamoto K. Source: Clin Oncol (R Coll Radiol). 2003 December; 15(8): 467-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14690002
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Epiphora induced by intermittent docetaxel (taxotere) in patients with non-small cell lung cancer. Author(s): Spell DW, Estephan FF, Lin JT, Jones DV Jr. Source: Cancer Investigation. 2003; 21(4): 550-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533445
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ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgenindependent human prostate cancer cells. Author(s): Zelivianski S, Spellman M, Kellerman M, Kakitelashvilli V, Zhou XW, Lugo E, Lee MS, Taylor R, Davis TL, Hauke R, Lin MF. Source: International Journal of Cancer. Journal International Du Cancer. 2003 November 10; 107(3): 478-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506750
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Erosive conjunctivitis and punctal stenosis secondary to docetaxel (taxotere). Author(s): Skolnick CA, Doughman DJ. Source: Eye & Contact Lens. 2003 April; 29(2): 134-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695719
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European experience of docetaxel and cisplatin in advanced gastric cancer. Author(s): Roth AD. Source: Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2002; 5 Suppl 1: 27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772884
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Evidence for in vivo synergism between docetaxel and gemcitabine in patients with metastatic breast cancer. Author(s): Alexopoulos A, Tryfonopoulos D, Karamouzis MV, Gerasimidis G, Karydas I, Kandilis K, Stavrakakis J, Stavrinides H, Georganta C, Ardavanis A, Rigatos G. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2004 January; 15(1): 95-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679126
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Exisulind-induced apoptosis in a non-small cell lung cancer orthotopic lung tumor model augments docetaxel treatment and contributes to increased survival. Author(s): Whitehead CM, Earle KA, Fetter J, Xu S, Hartman T, Chan DC, Zhao TL, Piazza G, Klein-Szanto AJ, Pamukcu R, Alila H, Bunn PA Jr, Thompson WJ. Source: Molecular Cancer Therapeutics. 2003 May; 2(5): 479-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748310
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Exudative hyponychial dermatitis associated with capecitabine and docetaxel combination chemotherapy for metastatic breast carcinoma: report of three cases. Author(s): Chen GY, Chang TW, Chen WC. Source: The British Journal of Dermatology. 2003 May; 148(5): 1071-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786853
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Factors affecting pharmacokinetic variability following doxorubicin and docetaxelbased therapy. Author(s): Rudek MA, Sparreboom A, Garrett-Mayer ES, Armstrong DK, Wolff AC, Verweij J, Baker SD. Source: European Journal of Cancer (Oxford, England : 1990). 2004 May; 40(8): 1170-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15110880
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Factors predicting docetaxel-related toxicity: experience at a single institution. Author(s): Massacesi C, Marcucci F, Rocchi MB, Mazzanti P, Pilone A, Bonsignori M. Source: J Chemother. 2004 February; 16(1): 86-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078005
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Fatal herpes simplex virus hepatitis complicating chemotherapy with weekly docetaxel. Author(s): Hofer S, Hunziker S, Tornillo L, Ludwig CU. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 340. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562665
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Filgrastim-mediated neutrophil recovery in patients with breast cancer treated with docetaxel and doxorubicin. Author(s): Meza LA, Green MD, Hackett JR, Neumann TA, Holmes FA. Source: Pharmacotherapy. 2003 November; 23(11): 1424-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620389
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Flavopiridol enhances the effect of docetaxel in vitro and in vivo in human gastric cancer cells. Author(s): Motwani M, Rizzo C, Sirotnak F, She Y, Schwartz GK.
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Source: Molecular Cancer Therapeutics. 2003 June; 2(6): 549-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12813134 •
Gemcitabine and docetaxel after failure of cisplatin-based chemotherapy in patients with carcinoma of unknown primary site. Author(s): Pouessel D, Culine S, Becht C, Romieu G, Fabbro M, Ychou M, Cupissol D, Pinguet F. Source: Anticancer Res. 2003 May-June; 23(3C): 2801-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926116
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Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Author(s): Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F. Source: Cancer. 2004 March 15; 100(6): 1257-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022294
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Gemcitabine and docetaxel in metastatic and neoadjuvant treatment of breast cancer. Author(s): Yardley DA. Source: Seminars in Oncology. 2004 April; 31(2 Suppl 5): 37-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15199531
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Gemcitabine and vinorelbine followed by docetaxel in patients with advanced nonsmall-cell lung cancer: a multi-institutional phase II trial of nonplatinum sequential triplet combination chemotherapy (JMTO LC00-02). Author(s): Hosoe S, Komuta K, Shibata K, Harada H, Iwamoto Y, Ohsaki Y, Morioka T, Origasa H, Fukushima M, Furuse K, Kawahara M. Source: British Journal of Cancer. 2003 February 10; 88(3): 342-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569374
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Gemcitabine combined with docetaxel in metastatic breast cancer. Author(s): Fumoleau P. Source: Seminars in Oncology. 2003 April; 30(2 Suppl 3): 15-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12722020
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Gemcitabine plus docetaxel administered every other week as first-line treatment of metastatic breast cancer: preliminary results from a phase II trial. Author(s): Pelegr A, Calvo L, Mayordomo JI, Florian J, Vazquez S, Arcusa A, MartnRichard M, Bayo JL, Virizuela J, Carrasco E, Anton A; Spanish Group for Breast Cancer Research (GEICAM). Source: Seminars in Oncology. 2004 April; 31(2 Suppl 5): 20-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15199528
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Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Author(s): Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Elledge R, Mohsin S, Osborne CK, Chamness GC, Allred DC, O'Connell P. Source: Lancet. 2003 August 2; 362(9381): 362-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12907009
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High incidence of severe hand-foot syndrome during capecitabine-docetaxel combination chemotherapy. Author(s): Park YH, Ryoo BY, Lee HJ, Kim SA, Chung JH. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 November; 14(11): 1691-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581282
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Immediate effects of docetaxel alone or in combination with epirubicin on cardiac function in advanced breast cancer. Author(s): Syvanen K, Ekholm E, Anttila K, Salminen E. Source: Anticancer Res. 2003 March-April; 23(2C): 1869-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820471
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Immunomodulatory effects of docetaxel on human lymphocytes. Author(s): Si MS, Imagawa DK, Ji P, Wei X, Holm B, Kwok J, Lee M, Reitz BA, Borie DC. Source: Investigational New Drugs. 2003 August; 21(3): 281-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578678
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Improved penetration of docetaxel into the brain by co-administration of inhibitors of P-glycoprotein. Author(s): Kemper EM, Verheij M, Boogerd W, Beijnen JH, van Tellingen O. Source: European Journal of Cancer (Oxford, England : 1990). 2004 May; 40(8): 1269-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15110893
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Improvement of paclitaxel-induced neuropathy by substitution of docetaxel for paclitaxel. Author(s): Rose PG, Smrekar M. Source: Gynecologic Oncology. 2003 November; 91(2): 423-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599877
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In vitro schedule-dependent interaction between docetaxel and gemcitabine in human gastric cancer cell lines. Author(s): Ricotti L, Tesei A, De Paola F, Ulivi P, Frassineti GL, Milandri C, Amadori D, Zoli W.
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Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 February; 9(2): 900-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576465 •
In vivo synergism between docetaxel and gemcitabine in patients with metastatic breast cancer: general concepts and future perspectives. Author(s): Alexopoulos A, Karamouzis MV, Rigatos G. Source: Seminars in Oncology. 2004 April; 31(2 Suppl 5): 25-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15199529
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Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer. Author(s): Horne MK 3rd, Figg WD, Arlen P, Gulley J, Parker C, Lakhani N, Parnes H, Dahut WL. Source: Pharmacotherapy. 2003 March; 23(3): 315-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627929
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Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study. Author(s): Wirth LJ, Lucca J, Ostler P, Fidias P, Lynch C, Janne PA, Herbst RS, Johnson BE, Sugarbaker DJ, Mathisen DJ, Lukanich JM, Choi NC, Berman SM, Skarin AT. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 May; 9(5): 1698-704. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738723
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Influence of neoadjuvant therapy with epirubicin and docetaxel on the expression of HER2/neu in patients with breast cancer. Author(s): Taucher S, Rudas M, Mader RM, Gnant M, Sporn E, Dubsky P, Roka S, Bachleitner T, Fitzal F, Kandioler D, Wenzel C, Steger GG, Mittlbock M, Jakesz R. Source: Breast Cancer Research and Treatment. 2003 December; 82(3): 207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703068
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Inhibition of tumor-associated fatty acid synthase hyperactivity induces synergistic chemosensitization of HER -2/ neu -overexpressing human breast cancer cells to docetaxel (taxotere). Author(s): Menendez JA, Lupu R, Colomer R. Source: Breast Cancer Research and Treatment. 2004 March; 84(2): 183-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999148
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Inhibitory effects of docetaxel on expression of VEGF, bFGF and MMPs of LS174T cell. Author(s): Guo XL, Lin GJ, Zhao H, Gao Y, Qian LP, Xu SR, Fu LN, Xu Q, Wang JJ.
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Source: World Journal of Gastroenterology : Wjg. 2003 September; 9(9): 1995-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970892 •
Interaction pharmacokinetics of pegylated liposomal doxorubicin (Caelyx) on coadministration with paclitaxel or docetaxel. Author(s): Briasoulis E, Karavasilis V, Tzamakou E, Rammou D, Soulti K, Piperidou C, Pavlidis N. Source: Cancer Chemotherapy and Pharmacology. 2004 May; 53(5): 452-7. Epub 2004 January 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749894
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Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel as secondline treatment for peritoneal carcinomatosis of gynaecological origin. Author(s): de Bree E, Romanos J, Michalakis J, Relakis K, Georgoulias V, Melissas J, Tsiftsis DD. Source: Anticancer Res. 2003 May-June; 23(3C): 3019-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926156
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Is docetaxel now an essential component of neoadjuvant breast chemotherapy? Author(s): Shahab N, Haider S. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 May 1; 22(9): 1766; Author Reply 1766-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15118007
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Is the second line data on the use of docetaxel in non-small cell lung cancer reproducible? Author(s): Sumpter K, Harper-Wynne C, Yeoh C, Popat S, Ashley S, Norton A, O'Brien M. Source: Lung Cancer (Amsterdam, Netherlands). 2004 March; 43(3): 369-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15165099
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Is weekly docetaxel an active and gentle chemotherapy in the treatment of metastatic breast cancer? Author(s): Maisano R, Mare M, Zavettieri M, Caristi N, Mesiti M, Scisca C, La Torre F. Source: Anticancer Res. 2003 March-April; 23(2C): 1923-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820480
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Laboratory and clinical evidence of synergistic cytotoxicity of sequential treatment with gemcitabine followed by docetaxel in the treatment of sarcoma. Author(s): Leu KM, Ostruszka LJ, Shewach D, Zalupski M, Sondak V, Biermann JS, Lee JS, Couwlier C, Palazzolo K, Baker LH.
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Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 May 1; 22(9): 1706-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15117993 •
Long-term suppression of lymphangitic lung metastasis from breast cancer using biweekly docetaxel: a case report. Author(s): Ninomiya J, Horiguchi J, Koibuchi Y, Yoshida T, Iijima K, Yoshida M, Takata D, Yokoe T, Iino Y, Morishita Y. Source: Breast Cancer. 2003; 10(4): 361-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14634516
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MAC-321, a novel taxane with greater efficacy than paclitaxel and docetaxel in vitro and in vivo. Author(s): Sampath D, Discafani CM, Loganzo F, Beyer C, Liu H, Tan X, Musto S, Annable T, Gallagher P, Rios C, Greenberger LM. Source: Molecular Cancer Therapeutics. 2003 September; 2(9): 873-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555706
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Measuring treatment preferences and willingness to pay for docetaxel in advanced ovarian cancer. Author(s): Dranitsaris G, Elia-Pacitti J, Cottrell W. Source: Pharmacoeconomics. 2004; 22(6): 375-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15099123
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Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial. Author(s): Betticher DC, Hsu Schmitz SF, Totsch M, Hansen E, Joss C, von Briel C, Schmid RA, Pless M, Habicht J, Roth AD, Spiliopoulos A, Stahel R, Weder W, Stupp R, Egli F, Furrer M, Honegger H, Wernli M, Cerny T, Ris HB. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 May 1; 21(9): 1752-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12721251
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Microangiopathic hemolysis refractory to plasmapheresis responding to docetaxel and cisplatin: a case report. Author(s): Marcoullis G, Abebe L, Jain D, Talusan R, Bhagwati N, Wiernik PH. Source: Medical Oncology (Northwood, London, England). 2002; 19(3): 189-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482131
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Microtubule-associated parameters as predictive markers of docetaxel activity in advanced breast cancer patients: results of a pilot study. Author(s): Bernard-Marty C, Treilleux I, Dumontet C, Cardoso F, Fellous A, Gancberg D, Bissery MC, Paesmans M, Larsimont D, Piccart MJ, Di Leo A.
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Source: Clinical Breast Cancer. 2002 December; 3(5): 341-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533264 •
Mode of action of docetaxel - a basis for combination with novel anticancer agents. Author(s): Herbst RS, Khuri FR. Source: Cancer Treatment Reviews. 2003 October; 29(5): 407-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972359
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Modified pharmacokinetic modulating chemotherapy using 5-fluorouracil, UFT, and taxotere (docetaxel) for advanced gastric cancer. Author(s): Tanaka K, Konishi N, Ohmori Y, Kobayashi M, Mohri Y, Tonouchi H, Kusunoki M. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 December; 8(6): 381-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663641
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Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locallyadvanced prostate cancer. Author(s): Hussain M, Smith DC, El-Rayes BF, Du W, Vaishampayan U, Fontana J, Sakr W, Wood D. Source: Urology. 2003 April; 61(4): 774-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670564
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Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate. Author(s): Amat S, Bougnoux P, Penault-Llorca F, Fetissof F, Cure H, Kwiatkowski F, Achard JL, Body G, Dauplat J, Chollet P. Source: British Journal of Cancer. 2003 May 6; 88(9): 1339-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12778058
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Neoadjuvant docetaxel in locally advanced breast cancer. Author(s): Hutcheon AW, Heys SD, Sarkar TK; Aberdeen Breast Group. Source: Breast Cancer Research and Treatment. 2003; 79 Suppl 1: S19-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868802
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Neoadjuvant docetaxel, cisplatin, 5-fluorouracil before concurrent chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck versus concomitant chemoradiotherapy: a phase II feasibility study. Author(s): Ghi MG, Paccagnella A, D'Amanzo P, Mione CA, Fasan S, Paro S, Mastromauro C, Carnuccio R, Turcato G, Gatti C, Pallini A, Nascimben O, Biason R, Oniga F, Medici M, Rossi F, Fila G.
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Source: International Journal of Radiation Oncology, Biology, Physics. 2004 June 1; 59(2): 481-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15145166 •
Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Author(s): Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Source: Clinical Breast Cancer. 2003 December; 4(5): 348-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715110
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Novel association with gemcitabine and docetaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracyclines: results of a multicenter phase II study. Author(s): Brandi M, Vici P, Lopez M, Valerio MR, Giotta F, Gebbia N, Schittulli F, Colucci G; Grupo Oncologico Italia Meridionale. Source: Seminars in Oncology. 2004 April; 31(2 Suppl 5): 13-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15199527
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Paclitaxel administered weekly in patients with docetaxel-resistant metastatic breast cancer: a single-center study. Author(s): Sawaki M, Ito Y, Hashimoto D, Mizunuma N, Takahashi S, Horikoshi N, Tada K, Kasumi F, Akiyama F, Sakamoto G, Imai T, Nakao A, Hatake K. Source: Tumori. 2004 January-February; 90(1): 36-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15143969
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Pharmacokinetic study of docetaxel in intraoperative hyperthermic i.p. chemotherapy for ovarian cancer. Author(s): de Bree E, Rosing H, Beijnen JH, Romanos J, Michalakis J, Georgoulias V, Tsiftsis DD. Source: Anti-Cancer Drugs. 2003 February; 14(2): 103-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569296
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Pharmacokinetics and tissue distribution of intraperitoneal docetaxel with different carrier solutions. Author(s): Mohamed F, Stuart OA, Sugarbaker PH. Source: The Journal of Surgical Research. 2003 July; 113(1): 114-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943819
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Phase 1 dose escalation study of docetaxel with filgrastim support in patients with advanced solid tumors. Author(s): Masters GA, Brockstein BE, Mani S, Ratain MJ.
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Source: Medical Oncology (Northwood, London, England). 2003; 20(1): 7-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665678 •
Phase 2 trial of single agent docetaxel in platinum and paclitaxel-refractory ovarian cancer, fallopian tube cancer, and primary carcinoma of the peritoneum. Author(s): Markman M, Zanotti K, Webster K, Peterson G, Kulp B, Belinson J. Source: Gynecologic Oncology. 2003 December; 91(3): 573-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675679
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Phase I and pharmacokinetic study of escalating dose of docetaxel administered with granulocyte colony-stimulating factor support in adult advanced solid tumors. Author(s): Goncalves A, Viret F, Ciccolini J, Genre D, Gravis G, Giovanini M, Camerlo J, Catalin J, Maraninchi D, Viens P. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 January; 9(1): 102-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538457
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Phase I dose and sequencing study of pegylated liposomal doxorubicin and docetaxel in patients with advanced malignancies. Author(s): Fracasso PM, Rodriguez LC, Herzog TJ, Fears CL, Goodner SA, Govindan R, Picus J, Rader JS, Tan BR, Arquette MA. Source: Cancer. 2003 August 1; 98(3): 610-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879480
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Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer. Author(s): Bleickardt E, Argiris A, Rich R, Blum K, McKeon A, Tara H, Zelterman D, Burtness B, Davies MJ, Murren JR. Source: Cancer Biology & Therapy. 2002 November-December; 1(6): 646-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12642688
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Phase I evaluation of docetaxel and topotecan for patients with advanced solid tumors. Author(s): Tsao AS, Shin DM, Palmer JL, Lee JS, Glisson BS. Source: Cancer. 2004 May 15; 100(10): 2240-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15139070
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Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer. Author(s): Shimizu T, Enomoto K, Haga S, Fukuda M, Iino Y, Ikeda T, Taguchi T. Source: Breast Cancer. 2003; 10(2): 140-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12736567
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Phase I study of weekly docetaxel infusion and concurrent radiation therapy for head and neck cancer. Author(s): Suzuki M, Nishimura Y, Nakamatsu K, Kanamori S, Koike R, Kawamoto M, Mori K. Source: Japanese Journal of Clinical Oncology. 2003 June; 33(6): 297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913084
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Phase I trial of docetaxel, carboplatin, and gemcitabine as first-line therapy for patients with high-risk epithelial tumors of mullerian origin. Author(s): Berkenblit A, Tung N, Kim Y, Feyler H, Niloff J, Berghe KV, Cannistra SA. Source: Gynecologic Oncology. 2003 June; 89(3): 486-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798716
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Phase I trial of weekly docetaxel and gemcitabine in patients with refractory malignancies. Author(s): Mekhail T, Hutson TE, Elson P, Budd GT, Srkalovic G, Olencki T, Peereboom D, Pelley R, Bukowski RM. Source: Cancer. 2003 January 1; 97(1): 170-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12491518
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Phase I trial of weekly docetaxel with concurrent three-dimensional conformal radiation therapy in the treatment of unfavorable localized adenocarcinoma of the prostate. Author(s): Kumar P, Perrotti M, Weiss R, Todd M, Goodin S, Cummings K, DiPaola RS. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 May 15; 22(10): 1909-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15143084
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Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer. Author(s): Kiura K, Ueoka H, Segawa Y, Tabata M, Kamei H, Takigawa N, Hiraki S, Watanabe Y, Bessho A, Eguchi K, Okimoto N, Harita S, Takemoto M, Hiraki Y, Harada M, Tanimoto M; Okayama Lung Cancer Study Group. Source: British Journal of Cancer. 2003 September 1; 89(5): 795-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942107
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Phase II clinical trial of carboplatin and docetaxel in patients with metastatic ovarian cancer: active combination with low incidence of peripheral neuropathy. Author(s): Vorobiof DA, Rapoport BL, Chasen MR, Cohen GL, Mahomed R, Karime M. Source: International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. 2003 May-June; 13(3): 287-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801257
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Phase II multicentre study of docetaxel plus 5-fluorouracil in patients with anthracycline-pretreated metastatic breast cancer. Author(s): Lortholary A, Delozier T, Monnier A, Bourgeois H, Bougnoux P, TubianaMathieu N, Riffaud JCh, Besson D, Lotz V, Gamelin E. Source: British Journal of Cancer. 2003 June 2; 88(11): 1669-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771978
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Phase II study of bi-weekly docetaxel and carboplatin with concurrent thoracic radiation therapy followed by consolidation chemotherapy with docetaxel plus carboplatin for stage III unresectable non-small cell lung cancer. Author(s): Sakai H, Yoneda S, Kobayashi K, Komagata H, Kosaihira S, Kazumoto T, Saito Y. Source: Lung Cancer (Amsterdam, Netherlands). 2004 February; 43(2): 195-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739040
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Phase II study of concurrent administration of doxorubicin and docetaxel as first-line chemotherapy for metastatic breast cancer. Author(s): Aihara T, Takatsuka Y, Itoh K, Sasaki Y, Katsumata N, Watanabe T, Noguchi S, Horikoshi N, Tabei T, Sonoo H, Hiraki S, Inaji H. Source: Oncology. 2003; 64(2): 124-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566909
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Phase II study of docetaxel and ifosfamide combination chemotherapy in non-smallcell lung cancer patients failing previous chemotherapy with or without paclitaxel. Author(s): Chen YM, Shih JF, Lee CS, Chen MC, Lin WC, Tsai CM, Perng RP. Source: Lung Cancer (Amsterdam, Netherlands). 2003 February; 39(2): 209-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581575
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Phase II study of docetaxel and irinotecan in metastatic or recurrent esophageal cancer: a preliminary report. Author(s): Govindan R, Read W, Faust J, Trinkaus K, Ma MK, Baker SD, McLeod HL, Perry MC. Source: Oncology (Huntingt). 2003 September; 17(9 Suppl 8): 27-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14569845
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Phase II study of docetaxel and topotecan combination chemotherapy in patients with advanced head and neck cancer. Author(s): Haddad RI, Van Echo DA. Source: Cancer Chemotherapy and Pharmacology. 2003 October; 52(4): 303-6. Epub 2003 June 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827298
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Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A
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Yorkshire breast cancer research group study. Author(s): Humphreys AC, Dent J, Rodwell S, Crawford SM, Joffe JK, Bradley C, Dodwell D, Perren TJ. Source: British Journal of Cancer. 2004 June 1; 90(11): 2131-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15150554 •
Phase II study of docetaxel in patients with relapsed or refractory malignant lymphoma. Author(s): Zekri JM, Hough RE, Davies JM, Molife R, Hancock BW, Lorigan PC. Source: British Journal of Cancer. 2003 May 6; 88(9): 1335-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12778057
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Phase II study of docetaxel plus enoxaparin in chemotherapy-naive patients with metastatic non-small cell lung cancer: preliminary results. Author(s): Robert F, Busby E, Marques MB, Reynolds RE, Carey DE. Source: Lung Cancer (Amsterdam, Netherlands). 2003 November; 42(2): 237-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568692
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Phase II study of docetaxel-vinorelbine in platinum-resistant, paclitaxel-pretreated ovarian cancer. Author(s): Aravantinos G, Bafaloukos D, Fountzilas G, Christodoulou C, Papadimitriou C, Pavlidis N, Kalofonos HP, Gogas H, Kosmidis P, Dimopoulos MA. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 July; 14(7): 1094-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853352
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Phase II study of gemcitabine plus docetaxel in advanced pancreatic cancer: a Hoosier Oncology Group study. Author(s): Schneider BP, Ganjoo KN, Seitz DE, Picus J, Fata F, Stoner C, Calley C, Loehrer PJ. Source: Oncology. 2003; 65(3): 218-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657595
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Phase II study of vinorelbine and low-dose docetaxel in chemotherapy-naive patients with hormone-refractory prostate cancer. Author(s): Koletsky AJ, Guerra ML, Kronish L. Source: Cancer Journal (Sudbury, Mass.). 2003 July-August; 9(4): 286-92. Erratum In: Cancer J. 2003 September-October; 9(5): 1 P Following Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12967139
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Phase II study of weekly docetaxel alone or in combination with trastuzumab in patients with metastatic breast cancer. Author(s): Raff JP, Rajdev L, Malik U, Novik Y, Manalo JM, Negassa A, Hopkins U, Sarta C, Sparano JA.
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Source: Clinical Breast Cancer. 2004 February; 4(6): 420-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023243 •
Phase II trial combining docetaxel and doxorubicin as neoadjuvant chemotherapy in patients with operable breast cancer. Author(s): Ganem G, Tubiana-Hulin M, Fumoleau P, Combe M, Misset JL, Vannetzel JM, Bachelot T, De Ybarlucea LR, Lotz V, Bendahmane B, Dieras V. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 November; 14(11): 1623-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581269
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Phase II trial of bevacizumab in combination with docetaxel in women with advanced breast cancer. Author(s): Ramaswamy B, Shapiro CL. Source: Clinical Breast Cancer. 2003 October; 4(4): 292-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651775
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Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58. Author(s): Smith RE, Anderson SJ, Brown A, Scholnik AP, Desai AM, Kardinal CG, Lembersky BC, Mamounas EP. Source: Clinical Breast Cancer. 2002 December; 3(5): 333-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533263
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Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium: a trial of the Eastern Cooperative Oncology Group. Author(s): Dreicer R, Manola J, Schneider DJ, Schwerkoske JF, George CS, Roth BJ, Wilding G; Eastern Cooperative Oncology Group. Source: Cancer. 2003 June 1; 97(11): 2743-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767086
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Phase II trial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancer. Author(s): Lordick F, von Schilling C, Bernhard H, Hennig M, Bredenkamp R, Peschel C. Source: British Journal of Cancer. 2003 August 18; 89(4): 630-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915869
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Phase I-II parallel study of docetaxel on a bimonthly schedule in refractory metastatic breast carcinoma. Author(s): Gebbia V, Borsellino N, Testa A, Tirrito ML, Ferrera P, Colombo A, Mauceri G, Marrazzo A, Porretto F, Musso M.
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Source: Breast Cancer Research and Treatment. 2003 January; 77(2): 99-108. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602908 •
Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. Author(s): Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 January 15; 22(2): 254-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722033
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Phenotypic and immunologic characteristics of docetaxel-mobilized peripheral blood stem cells in mice. Author(s): Ojeifo JO, Wu AG, Herscowitz HB, Meehan KR. Source: Journal of Hematotherapy & Stem Cell Research. 2003 April; 12(2): 189-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804178
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Phosphatidylcholine-derived phosphatidic acid and diacylglycerol are involved in the signaling pathways activated by docetaxel. Author(s): Maestre N, Bezombes C, Plo I, Levade T, Lavelle F, Laurent G, Jaffrezou JP. Source: Journal of Experimental Therapeutics & Oncology. 2003 January-February; 3(1): 36-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724857
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Population pharmacokinetics of weekly docetaxel in patients with advanced cancer. Author(s): Slaviero KA, Clarke SJ, McLachlan AJ, Blair EY, Rivory LP. Source: British Journal of Clinical Pharmacology. 2004 January; 57(1): 44-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678339
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Population-based pharmacoeconomic model for adopting capecitabine/docetaxel combination treatment for anthracycline-pretreated metastatic breast cancer. Author(s): Verma S, Ilersich AL. Source: The Oncologist. 2003; 8(3): 232-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12773745
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Potentiation of docetaxel antitumor activity by batimastat against mouse forestomach carcinoma. Author(s): Gu B, Wu D, Lu H, Li M, Gao H, Wan Y.
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Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 2001 December; 16(4): 223-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12903761 •
Prediction of response to docetaxel by quantitative analysis of class I and III betatubulin isotype mRNA expression in human breast cancers. Author(s): Hasegawa S, Miyoshi Y, Egawa C, Ishitobi M, Taguchi T, Tamaki Y, Monden M, Noguchi S. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 August 1; 9(8): 2992-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12912947
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Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer. Author(s): Katayama H, Ueoka H, Kiura K, Tabata M, Kozuki T, Tanimoto M, Fujiwara T, Tanaka N, Date H, Aoe M, Shimizu N, Takemoto M, Hiraki Y. Source: British Journal of Cancer. 2004 March 8; 90(5): 979-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14997193
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Preparation, characterization, and preliminary application of fibrinogen-coated olive oil droplets for the targeted delivery of docetaxel to solid malignancies. Author(s): Jakate AS, Einhaus CM, DeAnglis AP, Retzinger GS, Desai PB. Source: Cancer Research. 2003 November 1; 63(21): 7314-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612529
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Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing docetaxel. Author(s): Immordino ML, Brusa P, Arpicco S, Stella B, Dosio F, Cattel L. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2003 September 4; 91(3): 417-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932719
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Primary systemic therapy (PST) of locally advanced breast cancer using Doxorubicin/Docetaxel combination. Author(s): Dank M, Zergenyi E, Domotori ZS, Lahm E, Kulka J. Source: Anticancer Res. 2003 May-June; 23(3C): 2879-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926127
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Prospective randomised phase II study of docetaxel versus paclitaxel administered weekly in patients with non-small-cell lung cancer previously treated with platinumbased chemotherapy. Author(s): Esteban E, Gonzalez de Sande L, Fernandez Y, Corral N, Fra J, Muniz I, Vieitez JM, Palacio I, Fernandez JL, Estrada E, Lacave AJ; Grupo Oncologico del Norte de Espana.
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Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 November; 14(11): 1640-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581272 •
Protracted administration of weekly docetaxel in metastatic breast cancer. Author(s): Kuroi K, Bando H, Saji S, Toi M. Source: Oncol Rep. 2003 September-October; 10(5): 1479-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883727
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PSK-mediated NF-kappaB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1. Author(s): Zhang H, Morisaki T, Nakahara C, Matsunaga H, Sato N, Nagumo F, Tadano J, Katano M. Source: Oncogene. 2003 April 10; 22(14): 2088-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687011
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Pulmonary toxicity during prostate cancer treatment with docetaxel and thalidomide. Author(s): Behrens RJ, Gulley JL, Dahut WL. Source: American Journal of Therapeutics. 2003 May-June; 10(3): 228-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756431
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Quality of life and pain relief during treatment with calcitriol and docetaxel in symptomatic metastatic androgen-independent prostate carcinoma. Author(s): Beer TM, Eilers KM, Garzotto M, Hsieh YC, Mori M. Source: Cancer. 2004 February 15; 100(4): 758-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14770432
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Quality of life assessment of second-line docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: results of a prospective, randomized phase III trial. Author(s): Dancey J, Shepherd FA, Gralla RJ, Kim YS. Source: Lung Cancer (Amsterdam, Netherlands). 2004 February; 43(2): 183-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739039
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Radiotherapy with concomitant weekly docetaxel for Stages III/IV oropharynx carcinoma. Results of the 98-02 GORTEC Phase II trial. Author(s): Calais G, Bardet E, Sire C, Alfonsi M, Bourhis J, Rhein B, Tortochaux J, Man YT, Auvray H, Garaud P. Source: International Journal of Radiation Oncology, Biology, Physics. 2004 January 1; 58(1): 161-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697434
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Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer. Author(s): Karasawa K, Shinoda H, Katsui K, Seki K, Kohno M, Hanyu N, Nasu S, Muramatsu H, Maebayashi K, Mitsuhashi N, Yoshihara T. Source: Anticancer Res. 2002 November-December; 22(6B): 3785-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552993
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Radiotherapy with concurrent docetaxel for advanced and recurrent breast cancer. Author(s): Karasawa K, Katsui K, Seki K, Kohno M, Hanyu N, Nasu S, Muramatsu H, Maebayashi K, Mitsuhashi N, Haga S, Kimura T, Takahashi I. Source: Breast Cancer. 2003; 10(3): 268-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955041
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Randomised phase II study of docetaxel/cisplatin vs docetaxel/irinotecan in advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group Study (WJTOG9803). Author(s): Yamamoto N, Fukuoka M, Negoro SI, Nakagawa K, Saito H, Matsui K, Kawahara M, Senba H, Takada Y, Kudoh S, Nakano T, Katakami N, Sugiura T, Hoso T, Ariyoshi Y. Source: British Journal of Cancer. 2004 January 12; 90(1): 87-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710212
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Randomised, multicentre phase II study assessing two doses of docetaxel (75 or 100 mg/m2) as second-line monotherapy for non-small-cell lung cancer. Author(s): Quoix E, Lebeau B, Depierre A, Ducolone A, Moro-Sibilot D, Milleron B, Breton JL, Lemarie E, Pujol JL, Brechot JM, Zalcman G, Debieuvre D, Vaylet F, Vergnenegre A, Clouet P. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2004 January; 15(1): 38-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679117
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Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC. Author(s): Rocha Lima CM, Rizvi NA, Zhang C, Herndon JE 2nd, Crawford J, Govindan R, King GW, Green MR; Cancer Leukemia Group B. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2004 March; 15(3): 410-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998842
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Randomized phase III trial of pemetrexed versus docetaxel in patients with nonsmall-cell lung cancer previously treated with chemotherapy. Author(s): Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr.
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Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 May 1; 22(9): 1589-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15117980 •
Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. Author(s): Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 15; 21(16): 3016-24. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837811
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Recurrent gastric adenocarcinoma with unusual metastatic localization and excellent response to docetaxel and 5-FU continuous infusion. Author(s): Thuss-Patience PC, Kretzschmar A, Krenn V, Dorken B, Reichardt P. Source: Onkologie. 2003 February; 26(1): 63-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624520
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Reducing the time interval between cycles using standard doses of docetaxel and lenogastrim support: a feasibility study. Author(s): Culine S, Romieu G, Fabbro M, Becht C, Cupissol D, Guillemare C, Bleuse JP, Lotz V, Gourgou S. Source: Cancer. 2004 July 1; 101(1): 178-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15222004
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Reply to “Radiation pneumonitis and docetaxel”. Author(s): Senan S. Source: Lung Cancer (Amsterdam, Netherlands). 2004 January; 43(1): 117-8; Author Reply 119-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698546
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Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. Author(s): Pegram MD, Pienkowski T, Northfelt DW, Eiermann W, Patel R, Fumoleau P, Quan E, Crown J, Toppmeyer D, Smylie M, Riva A, Blitz S, Press MF, Reese D, Lindsay MA, Slamon DJ. Source: Journal of the National Cancer Institute. 2004 May 19; 96(10): 759-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15150304
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Retrospective analysis of safety and efficacy of low-dose docetaxel 60 mg/m2 in advanced non-small cell lung cancer patients previously treated with platinum-based chemotherapy.
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Author(s): Nakamura Y, Kunitoh H, Kubota K, Sekine I, Yamamoto N, Tamura T, Kodama T, Saijo N. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 October; 26(5): 459-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14528070 •
Reversible life-threatening encephalopathy in the absence of hepatic failure following conventional doses of docetaxel. Author(s): Guglani S, Farrugia D, Elsdon M, Parmar M, Owen JR. Source: Clin Oncol (R Coll Radiol). 2003 May; 15(3): 160-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801056
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Safety and activity of docetaxel and trastuzumab in HER2 overexpressing metastatic breast cancer: a pilot phase II study. Author(s): Montemurro F, Choa G, Faggiuolo R, Sperti E, Capaldi A, Donadio M, Minischetti M, Salomone A, Vietti-Ramus G, Alabiso O, Aglietta M. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 February; 26(1): 95-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576933
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Salvage treatment of metastatic breast cancer with docetaxel and carboplatin. A multicenter phase II trial. Author(s): Mavroudis D, Alexopoulos A, Malamos N, Ardavanis A, Kandylis C, Stavrinidis E, Kouroussis Ch, Agelaki S, Androulakis N, Bozionelou V, Georgoulias V. Source: Oncology. 2003; 64(3): 207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12697959
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Salvage treatment with docetaxel for recurrent epithelial ovarian cancer. Author(s): Niwa Y, Nakanishi T, Kuzuya K, Nawa A, Mizutani S. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 December; 8(6): 343-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663634
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Second line therapy with weekly low-dose docetaxel for pretreated non-small-cell lung carcinoma patients: a multicenter Italian phase II study. Author(s): Ardizzoia A, Acquati M, Fagnani D, Giordano M, Visini M, Scanni A, Quattrone A, Fusco O, Vergani C, Casartelli C, Tagliabue P, Malugani F; POLONORD Group. Source: Lung. 2004; 182(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752667
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Semi-synthesis of an O-glycosylated docetaxel analogue. Author(s): Nikolakakis A, Haidara K, Sauriol F, Mamer O, Zamir LO.
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Source: Bioorganic & Medicinal Chemistry. 2003 April 3; 11(7): 1551-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12628678 •
Sequential doxorubicin and docetaxel as first-line treatment in metastatic breast cancer: a GEICAM-9801 phase II study. Author(s): Alba E, Ribelles N, Anton A, Perez-Carrion R, Lopez-Vega JM, Llanos M, Pelegri A, Florian J, Menendez M, Godes MJ; GEICAM. Source: Breast Cancer Research and Treatment. 2003 January; 77(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602899
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Severe nail changes due to Docetaxel treatment. Author(s): Rafi L, Friedrich M, Tilgen W, Reichrath J. Source: European Journal of Dermatology : Ejd. 2003 November-December; 13(6): 610-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14721789
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Skin toxicity as a risk factor for major infections in breast cancer patients treated with docetaxel. Author(s): Poikonen P, Sjostrom J, Klaar S, Nittby LT, Sigurdsson H, Madsen EL, Joensuu H, Blomqvist C. Source: Acta Oncologica (Stockholm, Sweden). 2004; 43(2): 190-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15163169
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Successful docetaxel tolerance induction. Author(s): Messaad D, Sablayrolles P, Pujol JL, Demoly P. Source: Allergy. 2003 December; 58(12): 1320-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616116
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Successful treatment of pulmonary metastasis and local recurrence of angiosarcoma with docetaxel. Author(s): Isogai R, Kawada A, Aragane Y, Tezuka T. Source: The Journal of Dermatology. 2004 April; 31(4): 335-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15187330
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Successful treatment of thrombocytopenia due to marrow metastases of breast cancer with weekly docetaxel. Author(s): Ballot J, McDonnell D, Crown J. Source: Journal of the National Cancer Institute. 2003 June 4; 95(11): 831-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783943
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Synthesis of C-3' methyl taxotere (docetaxel). Author(s): Lucatelli C, Viton F, Gimbert Y, Greene AE.
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Source: The Journal of Organic Chemistry. 2002 December 27; 67(26): 9468-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492357 •
Synthesis of novel macrocyclic docetaxel analogues. Influence of their macrocyclic ring size on tubulin activity. Author(s): Querolle O, Dubois J, Thoret S, Roussi F, Montiel-Smith S, Gueritte F, Guenard D. Source: Journal of Medicinal Chemistry. 2003 August 14; 46(17): 3623-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904066
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The effect of granisetron on in vitro metabolism of paclitaxel and docetaxel. Author(s): Watanabe Y, Nakajima H, Nozaki K, Hoshiai H, Noda K. Source: Cancer Journal (Sudbury, Mass.). 2003 January-February; 9(1): 67-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602770
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The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. Author(s): Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project Protocol B-27. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 November 15; 21(22): 4165-74. Epub 2003 October 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559892
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The effectiveness of scalp cooling in preventing alopecia for patients receiving epirubicin and docetaxel. Author(s): Macduff C, Mackenzie T, Hutcheon A, Melville L, Archibald H. Source: European Journal of Cancer Care. 2003 June; 12(2): 154-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12787013
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The evolving role of docetaxel in the management of androgen independent prostate cancer. Author(s): Khan MA, Carducci MA, Partin AW. Source: The Journal of Urology. 2003 November; 170(5): 1709-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532760
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The mechanism of action of docetaxel (Taxotere) in xenograft models is not limited to bcl-2 phosphorylation. Author(s): Kraus LA, Samuel SK, Schmid SM, Dykes DJ, Waud WR, Bissery MC. Source: Investigational New Drugs. 2003 August; 21(3): 259-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578676
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The treatment of multiple myeloma with docetaxel (an ECOG study). Author(s): Friedenberg WR, Graham D, Greipp P, Blood E, Winston RD. Source: Leukemia Research. 2003 August; 27(8): 751-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801534
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Trastuzumab and docetaxel for metastatic breast cancer: an experience from a cancer centre in India. Author(s): Julka PK, Sharma DN, Mukhopadhyay P, Rath GK. Source: Clin Oncol (R Coll Radiol). 2004 April; 16(2): 115-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15074734
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Trastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma: final results from the California Cancer Consortium Screening and Phase II Trial. Author(s): Lara PN Jr, Chee KG, Longmate J, Ruel C, Meyers FJ, Gray CR, Edwards RG, Gumerlock PH, Twardowski P, Doroshow JH, Gandara DR. Source: Cancer. 2004 May 15; 100(10): 2125-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15139054
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Two-dimensional radiotherapy and docetaxel in treatment of stage III non-small cell lung carcinoma: no good survival due to radiation pneumonitis. Author(s): Dincbas FO, Atalar B, Koca S. Source: Lung Cancer (Amsterdam, Netherlands). 2004 February; 43(2): 241-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739045
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Unknown primary carcinoma: a feasibility assessment of combination chemotherapy with cisplatin and docetaxel. Author(s): Mukai H, Watanabe T, Ando M, Katsumata N. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 February; 8(1): 23-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601538
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Vesicant-type reaction due to docetaxel extravasation. Author(s): Ho CH, Yang CH, Chu CY. Source: Acta Dermato-Venereologica. 2003; 83(6): 467-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14690348
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Vinorelbine and cisplatin for metastatic breast cancer: a salvage regimen in patients progressing after docetaxel and anthracycline treatment. Author(s): Vassilomanolakis M, Koumakis G, Demiri M, Missitzis J, Barbounis V, Efremidis AP. Source: Cancer Investigation. 2003; 21(4): 497-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533438
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Vinorelbine and docetaxel as first-line chemotherapy in metastatic breast cancer. Author(s): Vassilomanolakis M, Koumakis G, Drufakou S, Aperis G, Demiri M, Barbounis V, Missitzis J, Efremidis AP. Source: Cancer Chemotherapy and Pharmacology. 2003 February; 51(2): 179-83. Epub 2002 December 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12647021
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Weekly administration of docetaxel for symptomatic metastatic hormone-refractory prostate carcinoma. Author(s): Gravis G, Bladou F, Salem N, Macquart-Moulin G, Serment G, Camerlo J, Genre D, Bardou VJ, Maraninchi D, Viens P. Source: Cancer. 2003 October 15; 98(8): 1627-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534878
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Weekly administration of docetaxel in patients with hormone-refractory prostate cancer: a pilot study on Japanese patients. Author(s): Kojima T, Shimazui T, Onozawa M, Tsukamoto S, Hinotsu S, Miyanaga N, Hattori K, Kawai K, Akaza H. Source: Japanese Journal of Clinical Oncology. 2004 March; 34(3): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078909
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Weekly docetaxel as neoadjuvant chemotherapy for stage II and III breast cancer: efficacy and correlation with biological markers in a phase II, multicenter study. Author(s): Estevez LG, Cuevas JM, Anton A, Florian J, Lopez-Vega JM, Velasco A, Lobo F, Herrero A, Fortes J. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 February; 9(2): 686-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576436
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Weekly docetaxel as second-line chemotherapy in advanced non-small cell lung cancer: phase II trial. Author(s): Serke M, Schoenfeld N, Loddenkemper R. Source: Anticancer Res. 2004 March-April; 24(2C): 1211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15154649
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Weekly docetaxel as second-line therapy for patients with advanced breast cancer resistant to previous anthracycline treatment. Author(s): Ramos M, Gonzalez-Ageitos A, Amenedo M, Gonzalez-Quintas A, Gamazo JL, Togores P, Losada G, Almanza C, Romero C, Gomez-Martin C. Source: J Chemother. 2003 April; 15(2): 192-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12797398
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Weekly docetaxel as second-line therapy in non-small cell lung cancer: a phase II study.
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Author(s): Rossi D, Graziano F, Ugolini M, Dennetta D, Alessandroni P, Catalano V, Giordani P, Fedeli SL, Fedeli A, Catalano G. Source: Tumori. 2004 January-February; 90(1): 50-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15143972 •
Weekly docetaxel for patients with platinum/paclitaxel/irinotecan-resistant relapsed ovarian cancer: a phase I study. Author(s): Terauchi F, Hirano T, Taoka H, Masaki K, Yamamoto Y, Ogura H, Kubo H. Source: International Journal of Clinical Oncology / Japan Society of Clinical Oncology. 2003 December; 8(6): 348-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663635
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Weekly docetaxel in elderly patients with prostate cancer: efficacy and toxicity in patients at least 70 years of age compared with patients younger than 70 years. Author(s): Beer TM, Berry W, Wersinger EM, Bland LB. Source: Clin Prostate Cancer. 2003 December; 2(3): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040860
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Weekly docetaxel in patients with pretreated metastatic breast cancer: a phase II trial. Author(s): Mey U, Gorschluter M, Ziske C, Kleinschmidt R, Glasmacher A, SchmidtWolf IG. Source: Anti-Cancer Drugs. 2003 March; 14(3): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634618
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Weekly docetaxel/paclitaxel in pretreated metastatic breast cancer. Author(s): Gennari A, Guarneri V, Landucci E, Orlandini C, Rondini M, Salvadori B, Ricci S, Conte PF. Source: Clinical Breast Cancer. 2002 December; 3(5): 346-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533265
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Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer. Author(s): Beer TM, Eilers KM, Garzotto M, Egorin MJ, Lowe BA, Henner WD. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 1; 21(1): 123-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12506180
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Weekly low-dose docetaxel in advanced hormone-resistant prostate cancer patients previously exposed to chemotherapy. Author(s): Petrioli R, Pozzessere D, Messinese S, Sabatino M, Di Palma T, Marsili S, Correale P, Manganelli A, Salvestrini F, Francini G.
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Source: Oncology. 2003; 64(4): 300-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759524 •
Weekly low-dose docetaxel in advanced non-small cell lung cancer previously treated with two chemotherapy regimens. Author(s): Petrioli R, Pozzessere D, Messinese S, Sabatino M, Ceciarini F, Marsili S, Correale P, Fiaschi AI, Voltolini L, Gotti G, Francini G. Source: Lung Cancer (Amsterdam, Netherlands). 2003 January; 39(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499099
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Weekly regimen of irinotecan/docetaxel in previously treated non-small cell lung cancer patients and correlation with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism. Author(s): Font A, Sanchez JM, Taron M, Martinez-Balibrea E, Sanchez JJ, Manzano JL, Margeli M, Richardet M, Barnadas A, Abad A, Rosell R. Source: Investigational New Drugs. 2003 November; 21(4): 435-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586211
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Weekly schedule of docetaxel in breast cancer: evaluation of response and toxicity. Author(s): Kuroi K, Bando H, Saji S, Toi M. Source: Breast Cancer. 2003; 10(1): 10-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525757
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.com: 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.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to docetaxel; 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: •
Herbs and Supplements Beta-Carotene Source: Healthnotes, Inc.; www.healthnotes.com Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Glutamine Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Healthnotes, Inc.; www.healthnotes.com N-Acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com Spleen Extracts Source: Healthnotes, Inc.; www.healthnotes.com Taurine Source: Healthnotes, Inc.; www.healthnotes.com Thymus Extracts Source: Healthnotes, Inc.; www.healthnotes.com
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 http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. PATENTS ON DOCETAXEL Overview 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.8 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 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. 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. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “docetaxel” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on docetaxel, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Docetaxel By performing a patent search focusing on docetaxel, 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
8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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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 docetaxel: •
DHA-pharmaceutical agent conjugates of taxanes Inventor(s): Bradley; Matthews O. (Laytonsville, MD), Shashoua; Victor E. (Brookline, MA), Swindell; Charles S. (Merion, PA), Webb; Nigel L. (Bryn Mawr, PA) Assignee(s): Neuromedica, Inc. (Conshohocken, PA) Patent Number: 5,795,909 Date filed: May 22, 1996 Abstract: The invention provides conjugates of cis-docosahexaenoic acid and taxanes useful in treating cell proliferative disorders. Conjugates of paclitaxel and docetaxel are preferred. Excerpt(s): Improving drug selectivity for target tissue is an established goal in the medical arts. In general, it is desirable to deliver a drug selectively to its target, so that dosage and, consequently, side effects can be reduced. This is particularly the case for toxic agents such as anti-cancer agents because achieving therapeutic doses effective for treating the cancer is often limited by the toxic side effects of the anti-cancer agent on normal, healthy tissue. The problems relating to lack of drug selectivity can be exemplified by Taxol.RTM. Taxol.RTM. (paclitaxel) was first isolated in 1971 from the bark of Taxus brevifolia and was approved in 1992 by the US Food and Drug Administration for treatment of metastatic ovarian cancer and later for breast cancer. Its mechanism of action is believed to involve promoting formation and hyperstabilization of microtubules, thereby preventing the disassembly of microtubules necessary for completion of cell division. It also has been reported that Taxol induces expression of cytokines, affects the activity of kinases and blocks processes essential for metastasis, in as yet uncharacterized mechanisms of action. Taxol has attracted unusually strong scientific attention, not only because of its unique antiproliferative mechanism of action, but also because it is active against nearly all cancers against which it has been tested and because it has been discovered to be an analog of numerous closely related compounds occurring naturally. These compounds, taxanes, are now recognized as a new class of anticancer compounds. Web site: http://www.delphion.com/details?pn=US05795909__
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Method for docetaxel synthesis Inventor(s): Sisti; Nicholas J. (Jeffersonville, PA), Swindell; Charles S. (Merion, PA) Assignee(s): Bryn Mawr College (Bryn Mawr, PA), NaPro BioTherapeutics, Inc. (Boulder, CO) Patent Number: 5,688,977 Date filed: March 19, 1996 Abstract: A method of producing docetaxel comprises the esterification of C7, C10 diCBZ 10-deacetyl baccatin III and an N-CBZ C2'-protected 3-phenyl isoserine side chain wherein C2' is protected by a hydrogenatable benyl-type protecting group. The C7, C10 carbobenzyloxy groups are then replaced with hydrogen and the carbobenzyloxy group at the C3' nitrogen site is replaced with t-butoxycarbonyl. Finally, the resulting compound is deprotected at C2' by replacing the benzyl-type protecting group with
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hydrogen to produce docetaxel. The esterification preferably employs an excess, such as six equivalents, of the side chain for each equivalent of the C7, C10 di-CBZ 10-deacetyl baccatin III. Benzyloxymethyl is the preferred protecting group at C2'. Excerpt(s): This invention generally relates to the synthesis of docetaxel from precursor compounds. More particularly, though, this invention concerns the synthesis of docetaxel using a suitably protected 10-deacetyl baccatin III backbone which is esterified with a suitably protected side chain acid to produce an intermediate that may thereafter be deprotected, acylated and further deprotected to produce docetaxel. Various taxane compounds are known to exhibit anti-tumor activity. As a result of this activity, taxanes have received increasing attention in the scientific and medical community. Primary among these is a compound known as "paclitaxel" which is also referred to in the literature as "taxol". Paclitaxel has been approved for the chemotherapeutic treatment of several different varieties of tumors, and the clinical trials indicate that paclitaxel promises a broad range of potent anti-leukemic and tumor-inhibiting activity. Paclitaxel is a naturally occurring taxane diterpenoid which is found in several species of the yew (genus Taxus, family Taxaceae). Unfortunately, the concentration of this compound is very low. The species of evergreen are also slow growing. Even though the bark of the yew trees typically exhibits the highest concentration of paclitaxel, the production of one kilogram of paclitaxel requires approximately 16,000 pounds of bark. Thus, the long term prospects for the availability of paclitaxel through isolation are discouraging. Web site: http://www.delphion.com/details?pn=US05688977__ •
Pharmaceutical composition based on taxoids Inventor(s): Durr; Manfred (Bergheim-Glessen, DE), Hager; Jorg-Christian (Cologne, DE), Wendel; Armin (Cologne, DE) Assignee(s): Rhone-Poulenc Rorer S.A. (Antony, FR) Patent Number: 5,670,536 Date filed: April 25, 1995 Abstract: This invention relates to a pharmaceutical composition comprising as active principle, docetaxel or a taxoid derived from docetaxel, one or more unsaturated phospholipids and a small amount of one or more negative phospholipids, allow the active principle to be formulated in high concentration and are suitable for administration by injection. Excerpt(s): The present invention relates to a pharmaceutical composition for administration by injection, comprising a therapeutic antitumor agent of the taxoid class. Active principles of the taxoid class are injectable, but their solubility in water is especially low. This makes it very difficult to produce a preparation for parenteral administration which is acceptable from a therapeutic standpoint. The taxoid class more especially includes Taxotere (docetaxel) as well as derivatives of this product. Web site: http://www.delphion.com/details?pn=US05670536__
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Pharmaceutical formulations of taxanes Inventor(s): Hausheer; Fredrick H. (Boerne, TX), Murali; Dhanabalan (San Antonio, TX), Seetharamulu; Peddaiahgari (San Antonio, TX) Assignee(s): BioNumerik Pharmaceuticals, Inc. (San Antonio, TX) Patent Number: 6,040,330 Date filed: January 8, 1999 Abstract: A pharmaceutical formulation of a taxane antineoplastic agent, particularly paclitaxel or docetaxel or a pharmaceutically acceptable salt thereof, and Nmethylpyrrolidin-2-one (NMP). The formulation may include other excipients and/or diluents, and is suitable for administration to patients with cancer. Excerpt(s): This invention relates to pharmaceutical formulations of taxanes, particularly the antitumor drugs Paclitaxel (Taxol) and Docetaxel (Taxotere), or derivatives thereof, and N-methylpyrrolidin-2-one (NMP). Taxanes, in particular, the two currently available drugs, Paclitaxel and Docetaxel, are potent antineoplastic agents. Taxanes are derived naturally or semi-synthetically from the bark or needles of certain yews. Paclitaxel was discovered in the late 1970s, and was found to be an effective antineoplastic agent with a mechanism of action different from existing chemotherapeutic agents. In particular, Paclitaxel, Docetaxel and other taxanes exert cytotoxic effects by enhancing the polymerization of tubulin, which is an essential protein in the formation of spindle microtubules. The result is the formation of very stable, nonfunctional tubules, which inhibits cell replication and leads to neoplasm cell death. Taxanes are recognized as effective agents in the treatment of many solid tumors which are refractory to other antineoplastic agents. Web site: http://www.delphion.com/details?pn=US06040330__
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Preparation of taxol and docetaxel through primary amines Inventor(s): Cheng; Xiaoqin (Broomfield, CO), Murray; Christopher K. (Longmont, CO), Peterson; S. Kent (Denver, CO), Zheng; Qun Y. (Superior, CO) Assignee(s): Hauser, Inc. (Boulder, CO) Patent Number: 5,679,807 Date filed: January 30, 1995 Abstract: The invention relates to a process for converting Taxol A, B and C to Taxol primary amine which can then be easily and efficiently converted to Taxol A or docetaxel, thereby significantly increasing the yield of these products from biomass. The method includes the removal of the amide from the side-chain with Schwartz's reagent to form an imine, followed by the hydrolysis of the imine to the primary amine. The primary amine can then be converted to Taxol A or docetaxel. New Taxol imine compounds and primary amine salts have been formed by this process. Excerpt(s): Our invention relates to a novel process for preparing the primary amine of Taxol, docetaxel and related compounds. Imines of Taxol, formed as intermediates in this process, and salts formed from the primary amine are also new. This invention relates generally to the field of preparing Taxol (which is also sometimes referred to as "paclitaxel" and a pharmaceutical composition of which is known as "TAXOL.RTM.", a registered trademark of the Bristol-Myers Squibb Company, Princeton, New Jersey) and certain of its precursors and related compounds including docetaxel (which is
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frequently referred to as "TAXOTERE.RTM.," a trademark of Rhone-Poulenc Rorer, Vitry-sur-Seine, France). The process of this invention also produces new taxane intermediate compounds, particularly certain imines and primary amine salts of Taxol and its derivatives. Taxol, a material occurring in nature, and extracted from Taxus brevifolia (i.e., the Pacific yew tree) and other biomass has been identified as having significant tubulin binding (Schiff, P. B., et al., "Promotion of Microtubule Assembly in vitro by Taxol," Nature, 277:665-67 (February 1979)) and, when delivered to the cell, cytotoxicological activity which has been demonstrated through Phase III clinical trials. Taxol A has been approved for treatment of refractory ovarian cancer and refractory breast cancer by the U.S. Food and Drug Administration (the "FDA"). Taxol A is also being investigated for the treatment of other forms of cancer. Because its mechanism of action is significantly different from that of other known cytotoxic agents, the development of Taxol has provided a significant new addition to the arsenal for treating cancer. Docetaxel, which acts in a similar manner, has also been identified as having cytotoxic activity. Docetaxel has not been approved for sale by the FDA, but it is still being evaluated in Phase III clinical trials. Web site: http://www.delphion.com/details?pn=US05679807__ •
Taxoid derivative and method of producing thereof Inventor(s): Hamada; Hiroki (Okayama, JP), Hara; Koji (Yokohama, JP), Hara; Kozo (Yokohama, JP), Mandai; Tadakatsu (Kurashiki, JP), Mikuni; Katsuhiko (Yokohama, JP), Okumoto; Hiroshi (Kurashiki, JP) Assignee(s): Ensuiko Sugar Refining Co., Ltd. (Yokohama, JP), Kaken Pharmaceutical Co., Ltd. (Tokyo, JP), Tadakatsu MANDAI (Kurashiki, JP) Patent Number: 5,767,297 Date filed: June 3, 1997 Abstract: A taxoid derivative wherein sugar is combined with any one of paclitaxel, docetaxel and 10-deacetyl-bacatin III via a spacer. A method of producing the taxoid derivative comprises protecting hydroxyl groups at specific position of paclitaxel or docetaxel by protective compound followed by reacting with tetrabenzyl acetyloxyglucoside, and then carrying out debenzyl and detriethylsilyl reactions. A method of producing the taxoid derivative comprises reacting paclitaxel or docetaxel with tetrabenzyl acetyloxyglucoside, and then carrying out debenzyl reaction. Excerpt(s): The present invention relates to a taxoid derivative and method of producing it and, in detail, a taxoid derivative of which physiological activity and solubility in water were improved by combining sugar with any one of paclitaxel, docetaxel and 10deacetyl-baccatin III via a spacer, and a method of producing the said derivative. Paclitaxel (trade name, Taxol)is a diterpene compound ›M. C. Wani et al.: J. Am. Chem. Soc., 93, 2325 (1971)!isolated from bark of Taxus brevifolia growing in North America and known as a powerful anticancer drug having an improving effect on a uncurable cancer by a hitherto known chemical therapy. Mechanism of controling cancer with paclitaxel is unique and, while other anticancer drugs control formation of microtubule which is a main component of spindle, that is a mitosis device, paclitaxel causes excess formation of microtubule and thereby, controls mitosis. Although paclitaxel is a powerful anticancer drug, its solubility in water is low, and its utility as a medical drug is limited. Because of this, use of a solubilizing agent and study and development, etc. to enhance its solubility by preparing derivatives are actively carried out, and any sufficient measure to solve this matter is not yet found. For example, paclitaxel is at
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present administered to a patient using a solubilizing agent "Cremophore", and 1 liter of the solution is administered for 6 hours every two weeks, a four-run of which is carried out, thus being a heavy burden on patients ›Eric K. Rowinsky et al., CANCER RESEARCH 49, 4640 (1989)! and also, side effects of the solubilizing agent becomes a problem. Web site: http://www.delphion.com/details?pn=US05767297__ •
Taxoid derivatives and process for producing the same Inventor(s): Hara; Koji (Kanagawa, JP), Hara; Kozo (Kanagawa, JP), Mandai; Tadakatsu (2-1-19-301, Kitagata, Okayama-shi 700, JP), Mikuni; Katsuhiko (Kanagawa, JP), Nakamura; Kosho (Kyoto, JP), Okumoto; Hiroshi (Okayama, JP), Tsuchiya; Yoshinori (Tokyo, JP), Umetsu; Teruhiko (Tokyo, JP) Assignee(s): Bio Research Corporation of Yokohama (JP), Ensuiko Sugar Refining Company, Ltd (JP), Kaken Pharmaceutical Company, Ltd. (JP), Mandai; Tadakatsu (JP) Patent Number: 6,306,893 Date filed: April 7, 2000 Abstract: An object of the invention is to develop galactose or mannose derivatives of docetaxel, etc. having improved solubility and physiological activity, to alleviate burden imposed on patients and to provide effective therapeutic drug for tumors.The present invention provides taxoid derivatives comprising any of paclitaxel, docetaxel and 10deacetyl-baccatin III to which galactose or mannose is linked through a spacer, and methods for producing taxoid derivatives comprising reacting paclitaxel, docetaxel or 10-deacetyl-baccatin III with tetrabenzyl acetyloxygalactoside or tetrabenzyl acetyloxymannoside, subjecting the product to debenzylation reaction, and optionally to detriethylsilylation reaction. Excerpt(s): The present invention relates to taxoid derivatives and process for producing the same and more particularly to taxoid derivatives having improved physiological activity and solubility in water by linking galactose or mannose to any one of paclitaxel, docetaxel and 10-deacetyl-baccatin III through a spacer, and process for producing the same. Paclitaxel is a diterpene compound isolated from the bark of a yew tree of North American growth (Taxus brevifolia) [M. C. Wani et al.: J. Am. Chem. Soc., 93, 2325 (1971)] andis apotent antitumor agent having improving effect against tumors that cannot be cured by conventional chemical therapy. The mechanism by which taxol controls a tumor is specific; it causes excessive formation of a microtubule to inhibit mitosis in contrast to many conventional antitumor agents that inhibit the formation of a microtubule, which is a major component of a spindle, mitotic apparatus. Although paclitaxel is an important antitumor agent, it is low solubility in water and hence its application as a therapeutic drug is limited. Accordingly, studies on improvement of its solubility by use of a solubilizing agent or converting it into derivatives have been made intensively. However, no satisfactory solution has been found yet. For example, currently paclitaxel is administered together with "Cremophor", a solubilizing agent. This is performed by administering 1 liter over 6 hours every 2 weeks, which is practiced for 4 cycles, and imposes the patient with a heavy burden [Eric K. Rowinsky et al.: CANCER RESEARCH, 49, 4640 (1989)] and in addition has the problem that the solubilizing agent has side effects. Web site: http://www.delphion.com/details?pn=US06306893__
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Use of docetaxel for treating cancers Inventor(s): Bellet; Robert E. (Elkins Park, PA), Vogel; Charles L. (Davie, FL) Assignee(s): Aventis Pharma S.A. (Antony, FR) Patent Number: 6,333,348 Date filed: April 6, 2000 Abstract: The present invention relates to a method of treating cancer, comprising administering a dose of docetaxel and a dose of rhuMAb HER2 to a patient in need thereof, wherein said dosages have a synergistic therapeutic effect when compared to the administration of docetaxel or rhuMAb HER2 alone. Excerpt(s): This present invention relates to a novel therapeutic and synergistic combination of antineoplastic agents which are useful in the treatment of cancer. The present invention relates more specifically to the use of docetaxel in combination with recombinant humanized anti-HER2 antibody, rhuMAb HER2, for the treatment of cancers. "drug" or "drugs" refers to the above-mentioned active ingredients or medicaments or pharmaceutical preparations containing them. Web site: http://www.delphion.com/details?pn=US06333348__
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Water soluble paclitaxel prodrugs Inventor(s): Li; Chun (Missouri City, TX), Wallace; Sidney (Houston, TX), Yang; David J. (Sugar Land, TX), Yu; Dong-Fang (Houston, TX) Assignee(s): PG-TXL Company, L. P. (Houston, TX) Patent Number: 5,977,163 Date filed: March 11, 1997 Abstract: Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble chelator, polyethylene glycol or polymer such as poly (1-glutamic acid) or poly (1-aspartic acid). Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis and for prediction of paclitaxel uptake by tumors and radiolabeled DTPA-paclitaxel tumor imaging. Other embodiments include the coating of implantable stents for prevention of restenosis. Excerpt(s): The present invention relates generally to the fields of pharmaceutical compositions to be used in the treatment of cancer, autoimmune diseases and restenosis. The present invention also relates to the field of pharmaceutical preparations of anticancer agents such as paclitaxel (Taxol) and doectaxel (Taxotere), in particular making paclitaxel water soluble by conjugating the drug to water soluble moieties. Paclitaxel, an anti-microtubule agent extracted from the needles and bark of the Pacific yew tree, Taxus brevifolia, has shown a remarkable anti-neoplastic effect in human cancer in Phase I studies and early Phase II and III trials (Horwitz et al., 1993). This has been reported primarily in advanced ovarian and breast cancer. Significant activity has been documented in small-cell and non-small cell lung cancer, head and neck cancers, and in metastatic melanoma. However, a major difficulty in the development of paclitaxel for clinical trial use has been its insolubility in water. Docetaxel is semisynthetically produced from 10-deacetyl baccatin III, a noncytotoxic precursor extracted from the needles of Taxus baccata and esterified with a chemically synthesized side chain (Cortes and Pazdur, 1995). Various cancer cell lines, including breast, lung,
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ovarian, and colorectal cancers and melanomas have been shown to be responsive to docetaxel. In clinical trials, docetaxel has been used to achieve complete or partial responses in breast, ovarian, head and neck cancers, and malignant melanoma. Web site: http://www.delphion.com/details?pn=US05977163__
Patent Applications on Docetaxel As of December 2000, U.S. patent applications are open to public viewing.9 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 docetaxel: •
Carbohydrate derivatives of paclitaxel and docetaxel, method for producing same and uses thereof Inventor(s): Page, Michel; (Quebec, CA) Correspondence: Ogilvy Renault; 1981 Mcgill College Avenue; Suite 1600; Montreal; QC; H3a2y3; CA Patent Application Number: 20040138142 Date filed: January 9, 2003 Abstract: The invention relates to new carbohydrate derivatives of paclitaxel and docetaxel with increased solubility in water as compared to the parent compounds, paclitaxel and docetaxel These derivatives are produced from naturally occurring precursor molecules which upon hydrolysis yield these natural precursors and the original paclitaxel and docetaxel molecules. The present invention also related to the composition and the use of such derivatives for cancer therapy. These derivatives may also be used in antifungal or antiviral therapy. Excerpt(s): The invention relates to carbohydrate paclitaxel and docetaxel derivatives to increase their solubility in water. Paclitaxel is a natural product extracted from the bark of the Pacific yew (Taxus brevifolia). It was thereafter found in other members of the Taxacae family including the yew of Canada (Taxus canadensis) found in Gaspesia, eastern Canada and Taxus baccata found in Europe whose needles contain paclitaxel and analogues and hence provide a renewable source of paclitaxel and derivatives. The crude extract was tested for the first time during the 60s and its active principle was isolated in 1971 by Wani et al. (Wani et al., J. Am. Chem. Soc. 93:2325-2327, 1971) who at the same time identified its chemical structure. It showed a wide range of activity over melanoma cells, leukemia, various carcinomas, sarcomas and non-Hodgkin lymphomas as well as a number of solid tumors in animals. Docetaxel is the active ingredient of Taxotere.TM. originally developed by Aventis Pharmaceuticals. It is prepared by semisynthesis from 10-Deacetylbaccatin III, a taxane abundant in the European yew Taxus baccata. Taxotere is currently approved in the United States to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy and for treatment of non-small cell lung cancer. Clinical studies have shown that paclitaxel and docetaxel are very effective anti cancer agents. They are both microtubule blockers, but unlike other drugs inhibiting the mitosis by interaction with microtubules such as colchicin, vincristin and podophyllotoxin, paclitaxel and docetaxel do not prevent
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This has been a common practice outside the United States prior to December 2000.
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tubulin assembly. They rather accelerate the tubulin polymerization and stabilize the assembled microtubules. The drugs act in a unique way which consists in binding to microtubules, preventing their depolymerization under conditions where usually depolymerization occurred (dilution, calcium, cold and microtubules disrupting drugs). Paclitaxel and docetaxel block the cell cycle at prophase which results in an accumulation of cells in G2+M. Because of their unique structures and mechanism of action, paclitaxel and docetaxel were submitted to clinical trials. Interesting activity against many tumors, especially breast cancer and ovarian cancer refractory to chemotherapy, has been observed. However, because of its poor solubility in water, paclitaxel had to be administered in ethanol, Cremophor-EL and 5% sucrose diluted in saline or water. Cremophor-EL was responsible for hypersensitivity reactions observed in several patients (Rowinsky, E. K., et al., J. Nat. Can. Inst., 82 (15), 1247-1259, 1990). Premedication with anti-histamines had to be administered in order to reduce the toxicity. Poor solubility of paclitaxel constitutes an important limitation to its administration to cancer patients. To increase paclitaxel availability, total and partial syntheses have been reported. The improvement of paclitaxel solubility was obtained by adjunction of solubilizing functions such as carbonyl or sulfonyl groups with good results. Some of the synthesized products were more active than paclitaxel, many others had a biological activity equivalent or slightly inferior to that of paclitaxel while being far more soluble in water (Kingston. D. G., Pharmacol. Ther. (England), 52(1) p1-34, 1991). The complexity of the paclitaxel chemical structure rendered its total synthesis very difficult but it was achieved simultaneously by two different groups. However the yield of this synthesis of the order of 2-4% will have little impact on the paclitaxel availability (Borman, S., Total synthesis of anticancer agent paclitaxel was achieved by two different routes (Borman et al., 1994, C & EN, 21:32-4)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Combination chemotherapy Inventor(s): Grove, William Richard; (Whitmore Lake, MI), Merriman, Ronald Lynn; (Ann Arbor, MI) Correspondence: Steven R. Eck; Warner-Lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030083366 Date filed: July 2, 2002 Abstract: Acetyldinaline in combination with docetaxel is synergistic for treating cancer. Excerpt(s): The invention concerns a method for treating tumors utilizing a combination of known oncolytic agents. The use of the agents together provides unexpectedly greater efficacy than employing the single agents alone. Cancer chemotherapy has advanced dramatically in recent years. Many tumors can be effectively treated utilizing compounds which are either naturally occurring products or synthetic agents. Cancer chemotherapy often entails use of a combination of agents, generally as a means of providing greater therapeutic effects and reducing the toxic effects that are often encountered with the individual agents when used alone. We have now discovered a unique combination of known oncolytic agents which exhibits a dramatic synergistic effect. The combination utilizes the agent acetyldinaline, together with docetaxel. The combination is especially effective in treating patients with solid tumors, especially nonsmall cell lung cancer and other advanced solid tumors.
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Combination of a taxane and a cyclin-dependent kinase Inventor(s): Bissery, Marie-Christine; (Vitry Sur Seine, FR) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20020182204 Date filed: March 21, 2002 Abstract: The invention relates to a pharmaceutical combination comprised of paclitaxel (Taxol.RTM.), docetaxel (Taxotere.RTM.), or derivatives of them, and a cyclindependent kinase inhibitor. It also relates to a method of administration of such a combination, where the taxane is given intermittently and the cyclin-dependent kinase is given repeatedly within the same cycle. Excerpt(s): This application relies on, and claims the benefit of, U.S. Provisional Application No. 60/277,948, filed Mar. 23, 2001, U.S. Provisional Application No. 60/302,692, filed Jul. 5, 2001, and U.S. Provisional Application No. 60/334,916, filed Dec. 4, 2001, the disclosures of all of which are hereby incorporated by reference. The present invention relates to combinations of Taxol.RTM., Taxotere.RTM., and their analogues and other compounds that are therapeutically useful in the treatment of neoplastic diseases. More especially, the invention relates to combinations of Taxol.RTM., Taxotere.RTM., and their analogues with anti-tumor agents, such as cyclin-dependent kinase inhibitors. Taxanes and taxoids constitute a family of naturally occurring diterpene compounds, including a potent antitumor drug, paclitaxel. Paclitaxel (Taxol.RTM.), originally isolated from the bark of the Pacific Yew tree (Taxus brevifolia), has been shown to be highly effective in adjuvant and neo-adjuvant therapies for patients with breast and ovarian cancers. More recently, its semisynthetic analogue, docetaxel (Taxotere.RTM.), has also been found effective in breast cancer chemotherapy. The diseases sensitive to this class of antitumor drugs also includes lung and colon cancers. Both Taxol.RTM. (paclitaxel) and Taxotere.RTM. (docetaxel) bind to tubulin, inhibit microtubule disassembly, and impair mitosis, thereby blocking progression through M phase of the cell cycle and facilitating apoptosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combination therapy for cancer Inventor(s): Wilson, William R.; (Auckland, NZ) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201; US Patent Application Number: 20010027210 Date filed: January 31, 2001 Abstract: This invention relates to a method of treating cancer, and particularly a method including the steps of administering to a mammal in need of such treatment, either simultaneously or sequentially, (i) a compound selected from a paclitaxel and docetaxel, and (ii) a compound of the formula 1or a pharmaceutically acceptable salt or ester thereof; wherein R.sub.1, R.sub.2 and R.sub.3 are each independently selected from
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the group consisting of H, C.sub.1--C.sub.6 alkyl, halogen, CF.sub.3, CN, NO.sub.2, NH.sub.2, OH, OR, NHCOR, NHSO.sub.2R, SR, SO.sub.2R or NHR, wherein each R is independently C.sub.1--C.sub.6 alkyl optionally substituted with one or more substituents selected from hydroxy, amino and methoxy, and wherein each of R.sub.1, R.sub.2 and R.sub.3 may be present at any of the available positions 1 to 8; and wherein in each of the carbocyclic aromatic rings in formula (I), up to two of the methine (-CH=) groups may be replaced by an aza (-N=) group; and wherein any two of R1, R2 and R3 may additionally together represent the group -CH =CH.multidot.CH =CH-, such that this group, together with the carbon or nitrogen atoms to which it is attached, forms a fused 6 membered aromatic ring. Excerpt(s): This invention relates to a method of treating cancer. The compound 5,6dimethylanthenone-4-acetic acid PMAA) is known to have significant antitumour activity against murine turmous and human turmours xenografted in immunodeficient mice. Studies have shown that this activity is largely, if not entirely, a consequence of inhibition of blood flow selectively within tumours. However, to date, DMXAA has shown little evidence of clinically viable anti-cancer activity in humans. The applicants have now surprisingly found that simultaneous or sequential administration of both a compound of the xanthenone acetic acid class (of which DMXAA is one) and either paclitaxel or docetaxel (both compounds of the taxane class of anticancer agents) results in an increase in antitumour activity such that the anticancer effect of the combination is much larger than for either agent alone, and greatly exceeds the sum of effects of the individual agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Conversion of 9-dihydro-13-acetylbaccatin III to baccatin III and 10-deacetyl baccatin III Inventor(s): Kasitu, Gertrude C.; (Debert, CA), Noah, Japheth W.; (Debert, CA) Correspondence: Scott D. Rothenberger; Dorsey & Whitney Llp; 220 South Sixth Street; Minneapolis; MN; 55402-1498; US Patent Application Number: 20010041803 Date filed: March 19, 2001 Abstract: Novel methods and synthetic intermediates to prepare baccatin III and 10deacetylbaccatin from readily available 9-dihydro-13-acetylbaccatin III are described. Selective protection and deprotection of the C-7 hydroxyl functionality provides an entry into facile synthesis of novel taxol intermediates, as well as, providing new methods for the preparation of paclitaxel and docetaxel in large scale. Selective oxidation of the C-9 hydroxyl without the need for protection of the C-7 hydroxyl is described. Excerpt(s): This application claims priority to U.S. Provisional Application Ser. No. 60/190,995, filed Mar. 21, 2000, entitled "Conversion of 9-Dihydro-13-acetylbaccatin III to Baccatin III and 10-Deacetylbaccatin III" by Gertrude C. Kasitu and Japheth W. Noah, the contents of which are incorporated herein by reference in their entirety. Paclitaxel was first isolated from the bark of the pacific yew, Taxus brevigolia (Wani et al., J. Am. Chem. Soc., 1971, 93, 2325-2327). Naturally occurring paclitaxel is in limited quantities and cannot meet the potential demand for therapeutic application. The limited supply of paclitaxel has restricted promising new drug developments. As a consequence of the limited supply of naturally occurring paclitaxel, strategies to increase the supply of
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paclitaxel by other means have been adopted. These include cell culture, total synthesis from simple starting materials, and semi-synthesis from readily available natural taxane derivatives. Although production via cell culture is very promising, the process to date has not reached large scale commercialization. The total synthesis of paclitaxel has been accomplished by a number of researchers (Holton; J. Am. Chem. Soc., 1994, 116, 1597 & 1599, J. Am. Chem. Soc., 1988, 110, 6558, Nicolaou; J. Am. Chem. Soc. 1995, 117, 653 and references cited therein, Danishefsky; J. Am. Chem. Soc., 1996, 118, 2843, Mukaiyama; Chem. Eur. J., 1999, 5, 121-161) however, none of the synthetic processes are practical commercially. The drawbacks of total synthesis include poor overall yields and lengthy complicated synthetic steps. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Differential patterns of gene expression that predict for docetaxel chemosensitivity and chemo resistance Inventor(s): Chang, Jenny C.; (Houston, TX), O'Connell, Peter; (Richmond, VA) Correspondence: Fulbright & Jaworski, Llp; 1301 Mckinney; Suite 5100; Houston; TX; 77010-3095; US Patent Application Number: 20040018527 Date filed: May 16, 2003 Abstract: The invention pertains to differential gene expression profiles for docetaxel responsiveness. The invention identifies molecular profiles in primary breast cancers that appear to predict response or lack of response to docetaxel. This invention provides methods involving prediction of docetaxel responsiveness as well as arrays for use in determining docetaxel responsivness. Excerpt(s): This applications claims the benefit of U.S. Provisional Application No. 60/381,141, filed May 17, 2002, which is hereby incorporated by reference in its entirety. The field of the invention relates to gene expression profiles in breast cancer cells. The field of the invention also relates to docetaxel sensitivity or resistance in breast cancer cells. Optimal systemic treatment (adjuvant therapy) after breast cancer surgery is the most crucial factor in reducing mortality in women with breast cancer. Adjuvant chemotherapy and hormonal treatment both reduce the risk of death in breast cancer patients. However, while estrogen receptor status predicts for response to honnonal treatments, there are no clinically useful predictive markers for chemotherapy response. All eligible women are therefore treated in the same manner even though de novo drug resistance will result in treatment failures in many breast cancer patients. The taxanes, docetaxel (Taxotere.TM.) and paclitaxel (Taxol.TM.), are a new class of anti-microtubule agents that are more effective than older drugs like the anthracyclines, although clinical trials with taxanes and anthracyclines in combination show that only a small subset of patients benefit from the addition of taxanes. Currently, there are no methods available to distinguish those patients who are likely to respond to taxanes from those who are not, and given the accepted practice of prescribing adjuvant treatment to most patients even if the average expected benefit is low, the a priori selection of appropriate patients most likely to benefit from adjuvant taxane therapy would represent a major advance in the clinical management of breast cancer today. A major impediment to study predictors of therapeutic efficacy in the adjuvant setting is the lack of surrogate markers for survival and, consequently, large numbers of patients with long-term follow-up are needed to conduct these studies.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of preparation of anticancer taxanes using 3-[(substituted-2-trialkylsilyl)ethoxycarbonyl]-5-oxazolidine carboxylic acids Inventor(s): Mahanti, Jyan Shankar; (Kalyani, IN), Sarkar, Subrata; (Kalyani, IN), Sharma, Arun Prakash; (Kalyani, IN) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030229135 Date filed: May 7, 2003 Abstract: This invention relates to a process for preparation of taxanes comprisingsubjecting 7,10-diprotected intermediates 7-O-(2-haloacyl) baccatin III 6c or 7,10-O-di-(2-haloacyl)-10-deacetylbaccatin III 6b to a step of coupling with (4S,5R)-3-[(2alkyl/aryl-2-trialkylsilyl) ethoxy-carbonyl]-4-aryl-2-substituted-1,3-oxazolidine-5carboxylic acid 1 in the presence of a condensation agent, an activating agent and an aromatic hydrocarbon to obtain 7-O-[2-(haloacyl)]-13-[(4S,5R)-4-aryl-2-su- bstituted-3(2unsubstituted/substituted-2-trialkylsilyl)-ethoxycarbonyl-1,3-oxazolidinyl-5carbonyl]baccatin III 7a or 7,10-di-O[2-(haloacyl)]-13-[(- 4S,5R)-4-aryl-2-substituted-3-(2unsubstituted/substituted-2-trialkylsilyl)ethoxy-carbonyl-1,3-oxazolidinyl-5carbonyl]-10-deacetylbaccatin III 7b;treating the coupled products 7-O-[2-(haloacyl)]-13[(4S,5R)-4-aryl-2-substituted-3-(2-substituted-2-trialkylsilyl)ethoxy-carbonyl-1,3oxazolidinyl-- S-carbonyl]baccatin III 7a or 7,10-di-0-[2[(haloacyl)]-13-[(4S,5R)-4-aryl-- 2substituted-3-(2-substituted-2-trialkylsilyl)ethoxycarbonyl-1,3-oxazolidinyl-5carbonyl]-10-deacetylbaccatin III 7b with tetraalkylammonium halide in a haloalkane to obtain free amine of structure 8;treating free amine 8 with acid chloride or acid anhydride in the presence of a base in a heterogeneous phase to obtain the intermediates of structure 9;subjecting the intermediates of compound 9 to the deprotection of 2haloacyl group under mild alkaline condition at -20 to +40.degree. C. for 6-24 h in the presence of ammonia or aliphatic amines or aromatic amines or their combination to obtain paclitaxel or docetaxel. Excerpt(s): The present invention relates to the process for the preparation of taxanes such as paclitaxel, docetaxel and their structural analogs using a novel oxazolidine carboxylic acid side chain. The present invention relates to a novel oxazolidine carboxylic acid and a process for its preparation. The invention further relates to a process for the preparation of paclitaxel, docetaxel and their structural analogs using such oxazolidine carboxylic acid. Paclitaxel is a diterpene taxane found in very low concentration in the bark of Pacific yew tree Taxus brevifolia. Therefore, a number of semi-synthetic strategies have been developed for its synthesis from more readily available 10-DAB. However, the taxane nucleus is highly prone to degradation and semisynthetic crude materials are often produced contaminated with structurally similar impurities, thereby necessitating elaborate purification procedure using HPLC. In view of the above facts) it becomes highly desirable to develop alternative routes for synthesis of paclitaxel which involves minimal degradation along the synthetic pathway. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents Inventor(s): Broder, Samuel; (Weston, FL), Duchin, Kenneth L.; (Fort Lauderdale, FL), Selim, Sami; (Irvine, CA) Correspondence: Lerner, David, Littenberg,; Krumholz & Mentlik; 600 South Avenue West; Westfield; NJ; 07090; US Patent Application Number: 20020058616 Date filed: April 10, 2001 Abstract: A method of increasing the bioavailability upon oral administration of a pharmacologically active target agent, particularly an antitumor or antineoplastic agent which exhibits poor or inconsistent oral bioavailability (e.g., paclitaxel, docetaxel or etoposide), comprises the oral co-administration to a mammalian patient of the target agent and an oral bioavailability-enhancing agent (e.g., cyclosporin A, cyclosporin D, cyclosporin F or ketoconazole). The enhancing agent may be administered orally from 0.5-24 hrs. prior to the oral administration of one or more doses of the target agent, substantially simultaneously with the target agent or both prior to and substantially simultaneously with the target agent. A method of treating mammalian patients suffering from diseases responsive to target agents with poor oral bioavailability, as well as oral dosage forms containing such target agents, combination oral dosage forms containing bioavailability-enhancing agents and target agents and kits containing enhancing and target agent dosage forms and dosing information for the coadministration of the same are also disclosed. Excerpt(s): This application is a continuation-in-part of co-pending application Ser. No. 08/608,776, filed Feb. 29, 1996, which claims the priority of provisional application Ser. No. 60/007,071, filed Oct. 26, 1995. This application incorporates material included in Disclosure Document No. 377063, filed Jun. 23, 1995, No. 386504, filed Dec. 11, 1995, No. 391109, filed Feb. 7, 1996, and No. 391228, filed Feb. 7, 1996. The invention relates to methods, compositions and kits for improving the oral bioavailability of pharmaceutical agents that are poorly absorbed from the gastrointestinal tract, and to methods of treatment of patients through the oral administration of such agents. One aspect of the invention relates to the use of cyclosporins to enhance the oral bioavailability of paclitaxel and related taxanes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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PROCESS FOR PREPARATION DOCETAXEL TRIHYDRATE
OF
PACLITAXEL
TRIHYDRATE
AND
Inventor(s): Mahanty, J.S.; (Nadia, IN), Sarkar, Subrata; (Nadia, IN), Sharma, Arun Prakash; (Nadia, IN) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20040116720 Date filed: April 22, 2003 Abstract: A process for the preparation of paclitaxel trihydrate and doctaxel trihydrate comprising (a) treating taxane selected from paclitaxel and docetaxel with a mixture of alkane and chlorinated alkane to obtain a crude product of 65-75% assay, (b) dissolving
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the crude product thus obtained in alkyl ketone followed by slow addition of an alkane to increase chromatographic purity, (c) dissolving the taxane of step (b) in an aliphatic nitrile at a temperature of 50-70.degree. C., (d) adding purified water to the product of step (c) to precipitate taxane trihydrate; and (e) filtering and drying the product of step (d) to obtain taxane trihydrate of C.P. >99.5% and 98-102% assay. Excerpt(s): Purification of semi-synthetic paclitaxel and docetaxel, which are well known and approved chemotherapeutic drugs for treatment of metastatic cancers is a challenging problem due to formation of a number of degradation products along the synthetic route. Furthermore, purified taxanes are found to undergo degradation, even under controlled storage condition. Therefore, it becomes desirable to develop stable crystalline forms of these molecules, which retain the desirable anti-cancer properties. Towards this end Rhone-Poulenc Rover, S. A., France has developed processes for preparation of trihydrates of paclitaxel and docetaxel. According to Authelin et al, U.S. Pat. No. 6,022,985 stability studies have shown that docetaxel trihydrate is stable at 4.degree. C., 25.degree. C., and 35.degree. C. in an atmosphere with 90% relative humidity upto 18 months without modification in its crystalline form. Under similar condition, anhydrous docetaxel slowly changes its crystalline form to the trihydrate form. This US Patent describes a process for the preparation of docetaxel trihydrate by crystallization of anhydrous docetaxel from a mixture of water and an aliphatic alcohol containing 1-3 carbon atom, specifically ethanol. The water/alcohol weight ratio used in this innovation is about 2/1. The crystals obtained thus, are dried under defined condition of temperature (about 40.degree. C.), pressure (4-7) kPa and relative humidity of about 80%. The crystallization was also performed in the presence of ascorbic acid. In U.S. Pat. No. 6,197,980 to Durand et al, a process for centrifugal partition chromatography of crude docetaxel in two partially miscible phases using an aliphatic hydrocarbon, an ester, an alcohol and water, is described. Docetaxel trihydrate is obtained by concentrating the column fractions. The process did not specify drying conditions. Similarly paclitaxel trihydrate is reported to have markedly superior stability in comparison to the anhydrous product. (Authelin el al U.S. Pat. No. 6,002,022). According to this invention, paclitaxel trihydrate is obtained from a mixture of water and an aliphatic alcohol containing upto three carbon atoms, specifically methanol. The water/alcohol weight ratio used in this process is between 3/1 to 1/3. The crystals, thus obtained, are dried at about 40.degree. C. under reduced pressure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for the preparation of taxanes such as paclitaxel, docetaxel and structurally similar analogs Inventor(s): Sarkar, Subrata; (Kalyani, IN), Sharma, Arun Prakash; (Kalyani, IN) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030045732 Date filed: August 7, 2002 Abstract: A process for the preparation of taxanes including paclitaxel, docetaxel, and structurally similar analogs, as well as intermediates produced by the process. Excerpt(s): This invention relates to a process for the preparation of taxanes such as paclitaxel, docetaxel and structurally similar analogs. This invention relates to a process for the preparation of taxanes such as paclitaxel, docetaxel and structurally similar
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analogs. The taxanes are very important anticancer drugs. Paclitaxel is an approved drug for refactory advanced ovarian cancer, breast cancer and most recently AIDSrelated Kaposi's sarcoma. It is a diterpene taxane found in very low concentration in the bark of Pacific yew tree Taxus brevifolia but its biogenetic precursor, 10deacetylbaccatin, 10-DAB 1 is found in relatively much higher concentration. Because of complex structure of taxane nucleus, total synthesis routes are very long and tedious and therefore appear uneconomical compared to semisynthesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Therapeutic compounds Inventor(s): Aleksov, Julian; (Lidingo, SE), Strelchenok, Oleg; (Lidingo, SE) Correspondence: Michael R. Ward; Morrison & Foerster Llp; 425 Market Street; San Francisco; CA; 94105-2482; US Patent Application Number: 20040048923 Date filed: November 15, 2002 Abstract: A group of new compounds, N-(all-trans-Retinoyl)-L-cysteic acid, N-(13-cisRetinoyl)-L-cysteic acid, N-(all-trans-Retinoyl)-L-cysteinesulf- inic acid, N-(13-cisRetinoyl)-L-cysteinesulfinic acid, N-(all-trans-Retinoyl)-L-homocysteic acid, N-(13-cisRetinoyl)-L-homocyst- eic acid, and sodium salts of these compounds, including sodium salts of their esters and amides, is shown to exhibit therapeutic effects per se, and which compounds in combination with cytotoxic compounds, such as docetaxel, paclitaxel, doxorubicin and mitoxantrone, exhibit a synergistic effect. These compounds make it possible to manufacture new formulations of poorly soluble pharmaceutical compounds, and the present invention discloses a process of manufacturing watersoluble formulations of such compounds, exemplified by docetaxel, and paclitaxel, exhibiting enhanced pharmacological activity, and formulations of water-soluble pharmaceuticals exemplified by doxorubicin and mitoxantrone, exhibiting improved therapeutic efficacy. Excerpt(s): This application claims priority to U.S. Provisional Patent Application Serial No. 60/398,200 filed Jul. 23, 2002, and Swedish Patent Application No. SE 0202311-7 filed Jul. 23, 2002, which are hereby incorporated by reference in their entirety. This invention relates to novel compounds having therapeutic properties in themselves, and being capable of potentiating the efficacy of other therapeutically active compounds, for example cytotoxic compounds used in the treatment of cancer. The novel compounds have been shown to possess a cell growth inhibiting property per se. In addition to this, these compounds have surprisingly been found to make it possible to manufacture new formulations of poorly soluble compounds, exemplified here by poorly soluble cytotoxic compounds, such as docetaxel and paclitaxel, the formulations exhibiting improved solubility and therapeutic efficacy. The compounds have also been found to make it possible to manufacture new formulations of other cytotoxic compounds, such as doxorubicin and mitoxantrone, exhibiting improved therapeutic efficacy. Further, the inventive compounds in saline in the presence of calcium, and in particular the corresponding cis- and trans-isoforms of a compound according to the invention have been found to exhibit therapeutic properties. Docetaxel is a representative of the taxoid family. [(2R,3S)-N-carboxy-3-phenylisoserine, N-tert-butyl ester, 13-ester with 5.beta.-20epoxy-1,2.alpha., 4,7.beta.,10.beta., 13.alpha.-hexahydroxytax- -11-en-9-one 4-acetate 2benzoate, trihydrate, the active ingredient in Taxotere.RTM., Rhone-Poulenc Rorer,
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Collegeville, Pa., USA] The compound may be prepared through synthesis from its chemical precursor, naturally present in the renewable needle biomass of yew plants. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of docetaxel for treating hepatoma Inventor(s): Chau, Gar-Yang; (Taipei, TW), Chi, Chin-Wen; (Taipei, TW), Lin, HengLiang; (Taipei, TW), Liu, Tsung-Yun; (Taipei, TW), Lui, Wing-Yiu; (Taipei, TW) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030158249 Date filed: February 27, 2002 Abstract: The present invention is based on the finding that docetaxel is significantly more active against hepatocellular carcinoma cells than paclitaxel at concentrations of up to 1.mu.M. It accordingly provides the use of docetaxel, or a hydrate thereof, in the manufacture of a medicament for use in the treatment of hepatocellular carcinoma. Excerpt(s): This invention relates to treatment of hepatocellular carcinoma. Hepatocellular carcinoma (HCC) is one of the most common cancers in Southeast Asia and African countries. In Taiwan, HCC is the leading cause of death in male cancer patients. The survival rate of HCC patients is very low. This is mainly due to lack of effective treatments. Irradiation and chemotherapies have not so far proved to be satisfactory; surgery is the most effective treatment for HCC. However, surgery is only appropriate for patients with small resectable tumours. Recently, antimitotic drugs such as paclitaxel have received renewed interest. Paclitaxel was originally isolated from the bark of the Yew tree. The antitumour effect of paclitaxel has been known since 1971. Paclitaxel inhibits tumour cell division by its action on microtubule assembly. In vitro analyses using tumour cells have revealed that paclitaxel arrests cells mainly in the G2/M phase of the cell cycle (Schiff PB and Horwitz SB, Proc. Natl. Acad. Sci 77, 15611565, 1980). Recent studies have shown that paclitaxel is effective against various malignant tumour cells such as brain tumour, gastric and prostate cancer, breast cancer, melanoma and ovarian cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Use of docetaxel/doxorubicin/cyclophosphamide in adjuvant therapy Inventor(s): Chakroun, Hichem; (Courbevoie, FR) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206; Mail Code: D303a; Bridgewater; NJ; 08807; US Patent Application Number: 20040014694 Date filed: May 16, 2003 Abstract: The present invention relates to a new method of adjuvant therapy in the treatment of early breast cancer, comprising administering six cycles of docetaxel, doxorubicin and cyclophosphamide to a patient in need thereof, wherein said dosages have a marked therapeutic effect when compared to other adjuvant therapies.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/380,850, filed May 17, 2002. This invention relates to a novel therapeutic use of a combination of taxotere with other antineoplastic agents in the adjuvant therapy of breast cancer. The present invention relates more specifically to the use of docetaxel in combination with doxorubicin and cyclophosphamide as adjuvant therapy in the treatment of breast cancer, i.e., early stages of breast cancer immediately after diagnoses by routine screening, such as mammography or other commonly used methods. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
WATER SOLUBLE PACLITAXEL DERIVATIVES Inventor(s): LI, CHUN; (MISSOURI CITY, TX), WALLACE, SIDNEY; (HOUSTON, TX), YANG, DAVID J.; (SUGAR LAND, TX), YU, DONG-FANG; (HOUSTON, TX) Correspondence: Ronald J. Kamis; Foley & Lardner; 3000 K Street N.W., Suite 500; Washington; DC; 20007-5109; US Patent Application Number: 20010034363 Date filed: March 30, 1998 Abstract: Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as polyglutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis. Excerpt(s): This application is a continuation-in-part of co-pending application U.S. Ser. No. 08/815,104, which is a continuation of U.S. Provisional Application No. 60/013,184. The present invention relates generally to the fields of pharmaceutical compositions to be used in the treatment of cancer, autoimmune diseases and restenosis. The present invention also relates to the field of pharmaceutical preparations of anticancer agents such as paclitaxel (Taxol.TM.) and docetaxel (Taxotere), in particular making paclitaxel water soluble by conjugating the drug to water soluble moieties. Paclitaxel, an antimicrotubule agent extracted from the needles and bark of the Pacific yew tree, Taxus brevifolia, has shown a remarkable anti-neoplastic effect in human cancer in Phase I studies and early Phase II and III trials (Horwitz et al., 1993). This has been reported primarily in advanced ovarian and breast cancer. Significant activity has been documented in small-cell and non-small cell lung cancer, head and neck cancers, and in metastatic melanoma. However, a major difficulty in the development of paclitaxel for clinical trial use has been its insolubility in water. 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 docetaxel, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “docetaxel” (or synonyms) into
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the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on docetaxel. You can also use this procedure to view pending patent applications concerning docetaxel. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 5. PERIODICALS AND NEWS ON DOCETAXEL Overview In this chapter, we suggest a number of news sources and present various periodicals that cover docetaxel.
News Services and Press Releases One of the simplest ways of tracking press releases on docetaxel is to search the news wires. 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. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “docetaxel” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to docetaxel. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “docetaxel” (or synonyms). The following was recently listed in this archive for docetaxel: •
Herceptin, Taxotere combo doubles cancer survival Source: Reuters Industry Breifing Date: September 24, 2003
•
First-line docetaxel improves survival in advanced non-small cell lung cancer Source: Reuters Industry Breifing Date: July 25, 2003
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•
Pemetrexed equivalent to docetaxel in NSCLC but more tolerable Source: Reuters Industry Breifing Date: June 03, 2003
•
Aventis' Taxotere boosts stomach cancer survival. Source: Reuters Industry Breifing Date: June 02, 2003
•
Aventis wins EU Taxotere approval Source: Reuters Industry Breifing Date: January 14, 2003
•
Progen tests lead oncologic in combination with Taxotere in phase I Source: Reuters Industry Breifing Date: September 05, 2002
•
Carboplatin, docetaxel and irinotecan improves lung cancer outcome Source: Reuters Industry Breifing Date: July 24, 2002
•
Capecitabine plus docetaxel improves survival in metastatic breast cancer Source: Reuters Industry Breifing Date: June 18, 2002
•
Trastuzumab plus docetaxel effective for HER-2 overexpressing breast cancer Source: Reuters Industry Breifing Date: April 03, 2002
•
Aventis' Taxotere to enter major new study for early breast cancer Source: Reuters Industry Breifing Date: October 22, 2001
•
BRCA2 status may predict response to docetaxel in breast cancer patients Source: Reuters Industry Breifing Date: August 13, 2001
•
Cell Pathways begin phase III trial of Aptosyn with Taxotere for lung cancer Source: Reuters Industry Breifing Date: March 02, 2001
•
Weekly docetaxel feasible for older patients with advanced lung cancer Source: Reuters Medical News Date: September 12, 2000
•
Twenty-minute breath test measures docetaxel elimination Source: Reuters Medical News Date: April 27, 2000
•
Colitis associated with use of docetaxel for metastatic breast cancer Source: Reuters Medical News Date: January 24, 2000
•
FDA panel recommends approval of docetaxel for non-small-cell lung cancer Source: Reuters Medical News Date: December 15, 1999
•
Inclusion of docetaxel improves response to neoadjuvant chemotherapy for large or advanced breast cancer Source: Reuters Medical News Date: December 13, 1999
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•
Primary chemotherapy for breast cancer: Sequential doxorubicin and docetaxel an option Source: Reuters Medical News Date: October 11, 1999
•
Second-line therapy with docetaxel prolongs survival in non-small-cell lung cancer patients Source: Reuters Medical News Date: May 24, 1999
•
Adjunctive docetaxel improves efficacy of two therapies for metastatic breast cancer Source: Reuters Medical News Date: December 17, 1998
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FDA committee backs expanded Taxotere use Source: Reuters Medical News Date: June 03, 1998
•
FDA Approves Taxotere For Treatment Of Metastatic Breast Cancer Source: Reuters Medical News Date: May 17, 1996
•
Rhone-Poulenc Rorer Has Promising Taxotere Results Source: Reuters Medical News Date: January 30, 1996
•
Rhone-Poulenc's Taxotere Taken Off FDA Agenda Source: Reuters Medical News Date: June 01, 1995 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 its search engine. 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. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “docetaxel” (or
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synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “docetaxel” (or synonyms). If you know the name of a company that is relevant to docetaxel, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. 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 “docetaxel” (or synonyms).
Academic Periodicals covering Docetaxel Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to docetaxel. In addition to these sources, you can search for articles covering docetaxel that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following 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.”
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CHAPTER 6. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for docetaxel. One such source 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 nonprofit 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 http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient 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, located at http://www.fda.gov/cder/da/da.htm. 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 Pharmacopeia (USP). Below, we have compiled a list of medications associated with docetaxel. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to docetaxel: Docetaxel •
Systemic - U.S. Brands: Taxotere http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202920.html
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. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult 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. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) 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. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a 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, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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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.11 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:12 •
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
•
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 cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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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
11
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). 12 See http://www.nlm.nih.gov/databases/databases.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
•
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
The NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “docetaxel” (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. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 2598 2 369 5 5 2979
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference 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.17 Simply search by “docetaxel” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
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.
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Coffee Break: Tutorials for Biologists18 Coffee Break is 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. Here you will find 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.19 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.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is 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 some 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/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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. 20 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.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. 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. Since new guidelines on docetaxel 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.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to docetaxel. 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. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to docetaxel. 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.
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You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are 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 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 this site located at http://www.guideline.gov/ by using the keyword “docetaxel” (or synonyms). Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and 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 NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. 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 docetaxel. 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. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on docetaxel can be purchased from NORD for a nominal fee.
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Additional Web Sources A number of Web sites are available to the public that often link to government sites. 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
•
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/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to docetaxel. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with docetaxel. 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 docetaxel. 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. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “docetaxel” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received
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your search results, click on the name of the organization for its description and contact information. 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 “docetaxel”. 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.” Type “docetaxel” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. 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 health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “docetaxel” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation 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. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
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 in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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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)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
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
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, 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/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
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/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), 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, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), 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: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_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, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. 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
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
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
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at 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).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
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
•
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
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DOCETAXEL DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making
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emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminocamptothecin: An anticancer drug that belongs to the family of drugs called topoisomerase inhibitors. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU]
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Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiosarcoma: A type of cancer that begins in the lining of blood vessels. [NIH] Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [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] Anticoagulants: Agents that prevent blood clotting. Naturally occurring agents in the blood are included only when they are used as drugs. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimitotic: Inhibiting or preventing mitosis. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU]
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Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antitumour: Counteracting tumour formation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the
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body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Batimastat: An anticancer drug that belongs to the family of drugs called angiogenesis inhibitors. Batimastat is a matrix metalloproteinase inhibitor. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Bevacizumab: A monoclonal antibody that may prevent the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental
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exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: 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 known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] 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] Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists
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mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Broad Ligament: A broad fold of peritoneum that extends from the side of the uterus to the wall of the pelvis. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Capecitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [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
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interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] 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-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardia: That part of the stomach surrounded by the esophagogastric junction, characterized by the lack of acid-forming cells. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiotoxicity: Toxicity that affects the heart. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Castration: Surgical removal or artificial destruction of gonads. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are
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made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrioles: Self-replicating, short, fibrous, rod-shaped organelles. Each centriole is a short cylinder containing nine pairs of peripheral microtubules, arranged so as to form the wall of the cylinder. [NIH] Ceramides: Members of the class of neutral glycosphingolipids. They are the basic units of sphingolipids. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in fabry disease. [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] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapeutics: Noun plural but singular or plural in constructions : chemotherapy. [EU]
Chemotherapy: Treatment with anticancer drugs. [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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronotherapy: The adaptation of the administration of drugs to circadian rhythms. The concept is based on the response of biological functions to time-related events, such as the low point in epinephrine levels between 10 p.m. and 4 a.m. or the elevated histamine levels between midnight and 4 a.m. The treatment is aimed at supporting normal rhythms or modifying therapy based on known variations in body rhythms. While chronotherapy is commonly used in cancer chemotherapy, it is not restricted to cancer therapy or to chemotherapy. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH]
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Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [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] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Colorectal: Having to do with the colon or the rectum. [NIH]
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Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH]
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Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH]
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Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyclosporins: A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection. [NIH] Cysteic Acid: Beta-Sulfoalanine. An amino acid with a C-terminal sulfonic acid group which has been isolated from human hair oxidized with permanganate. It occurs normally in the outer part of the sheep's fleece, where the wool is exposed to light and weather. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
De novo: In cancer, the first occurrence of cancer in the body. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or
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involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Deoxycytidine: A drug that protects healthy tissues from the toxic effects of anticancer drugs. [NIH] Deoxycytidine Kinase: An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (Herpesvirus hominis). EC 2.7.1.74. [NIH]
Deoxycytidine Monophosphate: Deoxycytidine (dihydrogen phosphate). A deoxycytosine nucleotide containing one phosphate group esterified to the deoxyribose moiety in the 2'-,3'or 5- positions. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diethylcarbamazine: An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease-Free Survival: Period after successful treatment in which there is no appearance of
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the symptoms or effects of the disease. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]
Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from combination drug therapy in which two or more drugs are administered separately for a combined effect. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH]
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Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Enoxaparin: A drug used to prevent blood clots. It belongs to the family of drugs called anticoagulants. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales.
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Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epirubicin: An anthracycline antibiotic which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, pancreatic cancer, gastric cancer, small-cell lung cancer and acute leukemia. It is equal in activity to doxorubicin but exhibits less acute toxicities and less cardiotoxicity. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelial ovarian cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estramustine: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH]
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Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exisulind: A drug that is being studied in the treatment and prevention of cancer. It has been shown to cause apoptosis (cell death) in cancerous and precancerous cells by acting through a group of cellular enzymes called cGMP phosphodiesterases. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Fabry Disease: Lysosomal storage disease caused by a deficiency of alpha-galactosidase A and resulting in an accumulation of globotriaosylceramide in the renal and cardiovascular systems. The disease is X-linked and is characterized by telangiectatic skin lesions, renal failure, and disturbances of the cardiovascular, gastrointestinal, and central nervous systems. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue
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development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH]
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Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH]
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Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Granisetron: A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Gynaecological: Pertaining to gynaecology. [EU] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver
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tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatoma: A liver tumor. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [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] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions
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upon subsequent exposure to that particular antigen. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [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
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agents. [EU] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [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] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [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] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interindividual: Occurring between two or more individuals. [EU] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH]
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Intraperitoneal chemotherapy: Treatment in which anticancer drugs are put directly into the abdominal cavity through a thin tube. [NIH] 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]
Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Lacrimal: Pertaining to the tears. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [NIH] Lesion: An area of abnormal tissue change. [NIH] Letrozole: An anticancer drug that belongs to the family of drugs called nonsteroidal aromatase inhibitors. Letrozole is used to decrease estrogen production and suppress the growth of estrogen-dependent tumors. [NIH] Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH]
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Leukemia: Cancer of blood-forming tissue. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Lipid: Fat. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]
Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Local therapy: Treatment that affects cells in the tumor and the area close to it. [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] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [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
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spread to other parts of the body. [NIH] Malignant mesothelioma: A rare type of cancer in which malignant cells are found in the sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammography: Radiographic examination of the breast. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Medical oncologist: A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, and biological therapy. A medical oncologist often serves as the main caretaker of someone who has cancer and coordinates treatment provided by other specialists. [NIH] Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the
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abdominal wall and conveys their blood vessels and nerves. [NIH] Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Miscible: Susceptible of being mixed. [EU] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [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
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hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial
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swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoadjuvant Therapy: Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutral Glycosphingolipids: A subclass of glycosphingolipids containing one or more sugars within their head group connected directly to a ceramide moiety. They consist of monoglycosyl-, and oligoglycosylsphingoids and monoglycosyland oligoglycosylceramides. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [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 nucleic acids and found in all living cells. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Normal Distribution: Continuous frequency distribution of infinite range. Its properties are as follows: 1) continuous, symmetrical distribution with both tails extending to infinity; 2) arithmetic mean, mode, and median identical; and 3) shape completely determined by the mean and standard deviation. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH]
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Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [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] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Oophorectomy: Surgery to remove one or both ovaries. [NIH] Orchiectomy: The surgical removal of one or both testicles. [NIH] Organ Specificity: Restriction of a characteristic or response to a particular organ of the body; it usually refers to that property of the immune response which differentiates one organ from another on the basis of antigen recognition, but the concept is not limited to immunology. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Oropharynx: Oral part of the pharynx. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing
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agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It is applied also in evaluating the quality of health care provided to patients. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perennial: Lasting through the year of for several years. [EU]
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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] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [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] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for
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the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [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] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]
Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH]
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Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymorphism: The occurrence together of two or more distinct forms in the same population. [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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [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] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH]
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Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [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] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH] Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. [NIH] Prostatic Neoplasms: Tumors or cancer of the prostate. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH]
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Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Pseudomembranous Colitis: Severe irritation of the colon. Caused by Clostridium difficile bacteria. Occurs after taking oral antibiotics, which kill bacteria that normally live in the colon. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Quality of Health Care: The levels of excellence which characterize the health service or health care provided based on accepted standards of quality. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation Oncology: A subspecialty of medical oncology and radiology concerned with the radiotherapy of cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies
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in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiosensitization: The use of a drug that makes tumor cells more sensitive to radiation therapy. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [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] 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: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [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] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH]
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Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [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] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU]
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Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequential treatment: One treatment after the other. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Single-agent: The use of a single drug or other therapy. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall
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in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] 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] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [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 s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH]
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Subacute: Somewhat acute; between acute and chronic. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. [NIH] Surgical castration: Surgical removal of the testicles (orchiectomy) or ovaries (oophorectomy) to stop the production of sex hormones. Decreasing the levels of hormones may stop the growth of certain cancers. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Taxanes: Anticancer drugs that inhibit cancer cell growth by stopping cell division. Also called antimitotic or antimicrotubule agents or mitotic inhibitors. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH]
Dictionary 183
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Phosphorylase: The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC 2.4.2.4. [NIH] Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [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] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU]
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Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [NIH] Translating: Conversion from one language to another language. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral resection: Surgery performed with a special instrument inserted through the urethra. Also called TUR. [NIH] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trastuzumab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. Trastuzumab blocks the effects of the growth factor protein HER2, which transmits growth signals to breast cancer cells. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH]
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Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [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] Unresectable: Unable to be surgically removed. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [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] Urothelium: The epithelial lining of the urinary tract. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH]
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Villus: Cell found in the lining of the small intestine. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vindesine: Vinblastine derivative with antineoplastic activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus, head, and neck, and Hodgkin's and non-Hodgkin's lymphomas. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]
187
INDEX A Abdominal, 141, 154, 164, 165, 167, 172, 173, 179 Acceptor, 141, 154, 171 Acute leukemia, 141, 157, 186 Acyl, 141, 149, 157 Adaptability, 141, 149 Adaptation, 141, 149 Adenocarcinoma, 31, 51, 56, 77, 85, 141, 161, 170, 176 Adenovirus, 10, 44, 141 Adjuvant, 6, 7, 15, 28, 31, 32, 44, 54, 64, 88, 104, 106, 111, 112, 141 Adjuvant Therapy, 31, 106, 111, 112, 141 Adverse Effect, 11, 141, 180 Affinity, 141, 142, 180 Agar, 141, 150, 174 Agonist, 142, 182 Algorithms, 142, 146 Alimentary, 142, 172 Alkaline, 107, 142, 147 Alkylating Agents, 142, 185 Allylamine, 142 Alopecia, 88, 142, 153 Alpha Particles, 142, 177 Alternative medicine, 117, 142 Amifostine, 41, 42, 142 Amine, 98, 107, 142, 162 Amino Acids, 142, 144, 148, 172, 175, 176, 180 Aminocamptothecin, 8, 142 Ammonia, 107, 142 Anaesthesia, 142, 163 Analog, 96, 143, 159 Anaplasia, 143, 176 Anemia, 143, 159, 169 Angiogenesis inhibitor, 18, 63, 143, 145 Angiosarcoma, 87, 143 Anhydrous, 109, 143 Animal model, 11, 13, 18, 143, 184 Anthracycline, 29, 36, 44, 55, 56, 65, 78, 81, 89, 90, 143, 153, 157 Antiangiogenic, 18, 58, 143 Antibiotic, 143, 153, 155, 157, 168, 181 Antibodies, 143, 161, 162, 163, 174, 177, 184 Anticoagulants, 143, 156 Antidote, 143, 165
Antiemetic, 143, 161 Antifungal, 102, 143, 153, 165 Antigen, 4, 19, 141, 143, 151, 162, 163, 164, 171 Anti-inflammatory, 143, 154, 160, 163 Antimetabolite, 143, 159, 168 Antimitotic, 11, 16, 111, 143, 182 Antineoplastic Agents, 12, 98, 101, 112, 142, 144, 186 Antioxidant, 144 Antiproliferative, 4, 19, 96, 144 Antitumour, 105, 111, 144 Antiviral, 102, 144, 164 Anus, 144, 150 Apoptosis, 4, 8, 10, 11, 12, 15, 19, 29, 30, 33, 63, 67, 68, 83, 104, 144, 148, 158 Aqueous, 144, 145, 153, 166 Aromatase, 144, 165 Arterial, 67, 142, 144, 176 Arteries, 144, 146 Arterioles, 144, 146, 147 Artery, 144, 146, 177 Asbestos, 144, 167, 168 Ascorbic Acid, 109, 144 Aspartic Acid, 101, 112, 144 Assay, 11, 15, 36, 53, 108, 144 Asymptomatic, 13, 34, 144, 161 Attenuated, 144, 154 Autacoids, 144, 163 Autoimmune disease, 101, 112, 145 B Bacteria, 141, 143, 145, 152, 158, 161, 168, 177, 181, 183, 184, 185 Bactericidal, 145, 157 Barbiturate, 145, 182 Base, 107, 145, 158, 165 Basophils, 145, 161 Batimastat, 81, 145 Benign, 145, 168, 170, 176, 178, 186 Bevacizumab, 80, 145 Bile, 5, 145, 159, 165, 166 Bile Acids, 145 Bile Acids and Salts, 145 Bile duct, 5, 145 Bile Pigments, 145, 165 Biliary, 5, 22, 33, 145 Biliary Tract, 22, 145 Bioavailability, 4, 21, 108, 145
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Biochemical, 38, 143, 145, 146, 159, 180 Biological Markers, 90, 145 Biological response modifier, 146, 164 Biological therapy, 146, 167 Biological Transport, 146, 154 Biomarkers, 5, 9, 10, 146 Biomass, 98, 99, 111, 146 Biopsy, 13, 146 Biotechnology, 19, 20, 117, 125, 146 Biotransformation, 25, 146 Bladder, 17, 33, 146, 176, 178, 179, 184, 185 Blood Coagulation, 146, 147 Blood Platelets, 146, 180, 183 Blood pressure, 146, 169, 180 Blood vessel, 143, 145, 146, 147, 152, 156, 166, 167, 168, 173, 185 Blot, 14, 146 Body Fluids, 146, 155, 180, 184 Bone Marrow, 141, 146, 150, 153, 160, 163, 166, 169, 180 Bone metastases, 16, 147 Bone Remodeling, 16, 147 Bone Resorption, 147 Bone scan, 16, 147 Bowel, 88, 147, 154, 164, 173, 181 Brachytherapy, 147, 164, 165, 177, 186 Broad Ligament, 147, 158 Buccal, 147, 166 C Calcifediol, 147 Calcitriol, 4, 19, 45, 83, 91, 147 Calcium, 103, 110, 144, 147, 151, 162, 165, 167, 172 Camptothecin, 147, 165 Capecitabine, 6, 20, 26, 36, 42, 49, 51, 56, 68, 70, 81, 116, 147 Capillary, 59, 147, 148, 185 Capillary Permeability, 59, 148 Capsules, 148, 155 Carbohydrate, 102, 148, 160, 175 Carbon Dioxide, 148, 160, 178 Carboplatin, 4, 7, 8, 13, 19, 35, 43, 48, 49, 50, 56, 59, 60, 64, 71, 77, 78, 84, 86, 116, 148 Carboxy, 110, 148 Carboxylic Acids, 107, 148 Carcinogenic, 142, 148, 175 Carcinogens, 148, 171 Cardia, 51, 148 Cardiac, 64, 70, 142, 148, 157, 169 Cardiotoxicity, 148, 157 Case report, 54, 66, 73, 148, 150
Case series, 148, 150 Caspase, 4, 12, 38, 148 Castration, 148 Causal, 148, 156, 161 Cause of Death, 13, 111, 148 Cell Cycle, 15, 19, 29, 53, 103, 104, 111, 149, 150, 153, 157, 177, 185 Cell Death, 10, 11, 12, 98, 144, 149, 157, 158, 170 Cell Differentiation, 15, 149 Cell Division, 96, 111, 145, 149, 157, 168, 174, 176, 182 Cell membrane, 146, 149, 173 Cell Size, 149, 159 Central Nervous System, 25, 149, 158, 159, 160, 180 Centrioles, 149, 176 Ceramides, 7, 149 Cervical, 31, 56, 62, 149 Cervix, 149 Chemotherapeutic agent, 4, 8, 13, 18, 98, 149 Chemotherapeutics, 18, 149 Cholesterol, 145, 149, 167, 182 Chromatin, 144, 149, 156, 166 Chronic, 149, 150, 161, 164, 182 Chronotherapy, 13, 149 Circadian, 149, 150 Circadian Rhythm, 149, 150 Cirrhosis, 38, 150 CIS, 16, 96, 110, 150 Clinical Medicine, 150, 175 Clinical study, 15, 150 Cloning, 146, 150 Coenzyme, 144, 150 Colchicine, 150, 184 Collagen, 150, 158, 159, 167 Colon, 104, 150, 151, 165, 177 Colony-Stimulating Factors, 150, 161 Colorectal, 17, 102, 150, 151 Colorectal Cancer, 102, 151 Combination chemotherapy, 22, 32, 34, 43, 44, 49, 57, 60, 65, 66, 68, 69, 70, 78, 89, 103, 151 Combination Therapy, 27, 36, 41, 56, 151 Comorbidity, 17, 151 Compassionate, 22, 151 Complement, 151 Complementary and alternative medicine, 47, 93, 151 Complementary medicine, 47, 151 Complete remission, 15, 66, 151, 178
189
Complete response, 15, 151 Computational Biology, 125, 152 Concomitant, 5, 58, 64, 74, 83, 152 Conjugated, 145, 152, 153 Conjugation, 146, 152 Conjunctiva, 152 Conjunctivitis, 67, 152 Connective Tissue, 144, 147, 150, 152, 159, 166, 167, 179 Consolidation, 58, 78, 152 Continuous infusion, 85, 152 Contraindications, ii, 152 Cooperative group, 9, 152 Coordination, 7, 152 Corticosteroids, 152, 160 Cortisone, 152, 154 Crystallization, 109, 152 Curative, 152, 183 Cutaneous, 7, 59, 152, 166 Cyclic, 153 Cyclin, 8, 15, 104, 153 Cyclophosphamide, 9, 42, 43, 49, 50, 60, 76, 80, 88, 111, 112, 153, 163 Cyclosporine, 21, 153 Cyclosporins, 108, 153 Cysteic Acid, 110, 153 Cytochrome, 66, 144, 153 Cytokine, 153, 159, 182 Cytoplasm, 144, 145, 149, 153, 156, 166, 169 Cytoprotection, 41, 153 Cytoskeleton, 153, 168 Cytostatic, 7, 153 Cytotoxic, 4, 5, 10, 17, 18, 98, 99, 110, 153, 177, 178 Cytotoxicity, 5, 11, 15, 72, 82, 142, 150, 153 D Daunorubicin, 153, 155 De novo, 106, 153 Degenerative, 153, 161 Deletion, 144, 154 Deoxycytidine, 10, 17, 154 Deoxycytidine Kinase, 17, 154 Deoxycytidine Monophosphate, 154 Dermatitis, 28, 34, 68, 154 Deuterium, 154, 162 Dexamethasone, 4, 11, 19, 154 Diagnostic procedure, 95, 118, 154 Diaphragm, 154, 174 Diethylcarbamazine, 154, 182 Diffusion, 21, 146, 148, 154 Digestion, 142, 145, 147, 154, 164, 166, 181
Digestive system, 154, 169 Digestive tract, 154, 180, 181 Dihydrotestosterone, 154, 178 Dilution, 103, 154 Diploid, 154, 174 Direct, iii, 13, 119, 150, 154, 178 Discrete, 147, 154 Disease-Free Survival, 7, 154 Disinfectant, 155, 157 Distal, 155, 173 Dosage Forms, 108, 155 Dose-limiting, 14, 155 Drug Combinations, 9, 155 Drug Interactions, 120, 155 Drug Resistance, 12, 13, 106, 155 Drug Tolerance, 155, 183 Duct, 155, 158, 179, 181 Duodenum, 145, 155, 181 E Efficacy, 4, 7, 11, 14, 17, 22, 30, 44, 48, 67, 73, 85, 90, 91, 103, 106, 110, 117, 155 Electrolyte, 155, 180 Electrons, 144, 145, 155, 165, 171, 177, 178 Embryo, 149, 155, 163 Empirical, 15, 156 Encapsulated, 156, 166 Encephalopathy, 86, 156 Endometrial, 60, 156 Endometrium, 156 Endothelial cell, 18, 19, 27, 156 Enoxaparin, 79, 156 Enterocytes, 5, 156 Environmental Exposure, 146, 156, 171 Environmental Health, 124, 126, 156 Enzymatic, 147, 151, 156, 157, 162, 167 Enzyme, 6, 144, 145, 147, 148, 150, 154, 156, 160, 163, 176, 178, 179, 183, 186 Eosinophils, 156, 161 Epidemiologic Studies, 146, 156 Epidermal, 38, 41, 54, 156, 167, 186 Epidermal Growth Factor, 41, 54, 156 Epidermal growth factor receptor, 54, 156 Epidermis, 156 Epidermoid carcinoma, 156, 181 Epigastric, 157, 172 Epinephrine, 149, 157, 170, 185 Epirubicin, 21, 23, 24, 25, 26, 56, 57, 61, 63, 64, 70, 71, 78, 88, 157 Epithelial, 5, 77, 86, 141, 146, 156, 157, 161, 162, 172, 176, 185 Epithelial Cells, 5, 156, 157, 162, 176 Epithelial ovarian cancer, 86, 157
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Epithelium, 156, 157, 176 Erythrocytes, 20, 143, 147, 157, 161 Escalation, 24, 41, 48, 49, 75, 76, 157 Esophageal, 62, 78, 157 Esophagus, 8, 51, 154, 157, 173, 181, 186 Esterification, 96, 157 Estradiol, 157 Estramustine, 16, 21, 22, 34, 43, 50, 51, 53, 55, 74, 157 Estrogen, 7, 106, 144, 157, 165, 180, 182 Estrogen receptor, 106, 157 Ethanol, 103, 109, 157 Etoposide, 7, 8, 108, 157 Eukaryotic Cells, 158, 163, 171 Excipients, 98, 158 Excitation, 158, 159, 170 Excitatory, 158, 160 Exfoliation, 158, 169 Exisulind, 21, 44, 68, 158 Exocrine, 158, 172 Exogenous, 146, 158, 176 External-beam radiation, 158, 165, 177, 186 Extracellular, 152, 158, 159, 167, 180 Extracellular Matrix, 152, 158, 159, 167 Extracellular Matrix Proteins, 158, 167 Extraction, 20, 35, 158 Extravasation, 89, 158 Eye Infections, 141, 158 F Fabry Disease, 149, 158 Fallopian tube, 76, 158 Family Planning, 125, 158 Fat, 145, 147, 158, 166 Fatty acids, 148, 158, 160, 176 Febrile, 32, 159 Fibrillation, 54, 159 Fibrinogen, 82, 159, 183 Fibroblasts, 15, 159, 164 Filgrastim, 29, 31, 34, 55, 68, 75, 159 Flavopiridol, 8, 68, 159 Flow Cytometry, 14, 159 Fluorescence, 159 Fluorescent Dyes, 159 Fluorouracil, 8, 29, 30, 34, 63, 64, 74, 78, 159 Folic Acid, 159, 165 G Gallbladder, 33, 141, 145, 154, 159 Gamma Rays, 159, 177, 178 Ganglia, 142, 159, 170 Gas, 142, 148, 154, 160, 162, 170, 179
Gas exchange, 160, 179 Gastric, 23, 34, 49, 51, 55, 60, 62, 63, 65, 66, 67, 68, 70, 74, 85, 111, 155, 156, 157, 160, 162 Gastrin, 160, 162 Gastrointestinal, 17, 24, 40, 51, 108, 144, 157, 158, 160, 180, 182, 184 Gastrointestinal tract, 108, 157, 160, 180, 184 Gene, 5, 10, 11, 12, 16, 17, 58, 70, 106, 141, 144, 145, 146, 160, 171, 172 Gene Expression, 5, 17, 106, 160 Gene Therapy, 10, 12, 58, 141, 160 Genotype, 160, 173 Gland, 40, 152, 160, 166, 172, 176, 179, 182, 183 Glucocorticoid, 12, 154, 160 Glucose, 144, 160, 161 Glutamate, 160 Glutamic Acid, 101, 112, 159, 160, 170 Glycerol, 160, 173 Glycerophospholipids, 160, 173 Glycoprotein, 17, 21, 53, 70, 159, 161, 184 Goblet Cells, 156, 161 Governing Board, 161, 175 Grade, 14, 161, 176 Graft, 153, 161, 163 Graft Rejection, 153, 161, 163 Granisetron, 88, 161 Granulocyte, 23, 38, 49, 50, 60, 61, 76, 150, 159, 161 Granulocyte Colony-Stimulating Factor, 23, 38, 49, 60, 61, 76, 150, 159, 161 Gynaecological, 37, 72, 161 H Haploid, 161, 174 Hemoglobin, 143, 157, 161 Hemoglobinopathies, 160, 161 Hemolysis, 73, 161 Hepatic, 25, 38, 86, 161 Hepatitis, 68, 161 Hepatitis C, 68, 161 Hepatocellular, 63, 111, 161 Hepatocellular carcinoma, 63, 111, 161 Hepatocytes, 161, 162 Hepatoma, 111, 162 Heredity, 160, 162 Herpes, 68, 154, 162 Herpes Zoster, 162 Histamine, 149, 162 Homeostasis, 147, 162 Homologous, 160, 162
191
Hormonal, 6, 34, 106, 162, 167 Hormonal therapy, 6, 34, 162, 167 Hormone therapy, 141, 162 Hybridomas, 162, 164 Hydrogen, 96, 141, 142, 145, 148, 154, 158, 162, 169, 170, 171, 177 Hydrolysis, 98, 102, 146, 150, 162, 175, 176 Hydroxylation, 147, 162 Hydroxyurea, 34, 162 Hyperaemia, 152, 162 Hyperbilirubinemia, 162, 165 Hypercalcemia, 19, 162 Hypersensitivity, 11, 26, 27, 38, 103, 162, 179 Hyperthermia, 163, 170 Hypnotic, 145, 163, 182 I Ifosfamide, 65, 78, 163 Immune response, 141, 143, 145, 152, 161, 163, 171, 182, 185, 186 Immune system, 146, 163, 185, 186 Immunization, 163 Immunohistochemistry, 14, 163 Immunologic, 81, 163, 178 Immunology, 141, 159, 163, 171 Immunosuppressant, 142, 159, 163, 168 Immunosuppressive, 153, 160, 163 Immunosuppressive therapy, 163 Immunotherapy, 7, 146, 163, 170 Implant radiation, 163, 164, 165, 177, 186 In situ, 62, 163 In Situ Hybridization, 62, 163 In vitro, 4, 5, 10, 13, 16, 19, 25, 26, 27, 31, 33, 36, 44, 68, 70, 73, 88, 99, 111, 160, 163 In vivo, 4, 5, 10, 11, 13, 16, 19, 27, 33, 44, 53, 67, 68, 71, 73, 160, 163 Incision, 163, 165, 176, 179 Indomethacin, 5, 163 Induction, 8, 11, 12, 16, 30, 63, 64, 71, 87, 163, 164 Induction therapy, 63, 164 Infection, 146, 158, 161, 164, 166, 170, 179, 184, 186 Inflammation, 143, 152, 154, 158, 161, 162, 164, 174, 181 Infusion, 41, 67, 77, 78, 164, 184 Inoperable, 55, 164 Inorganic, 150, 164, 174 Insight, 12, 14, 164 Interferon, 8, 27, 34, 164 Interferon-alpha, 27, 34, 164 Interindividual, 22, 164
Interleukin-6, 40, 164 Intermittent, 67, 164 Internal radiation, 164, 165, 177, 186 Interstitial, 36, 147, 164, 165, 186 Intestinal, 5, 147, 156, 164, 172 Intestine, 145, 147, 151, 164, 165 Intracellular, 13, 164, 167 Intramuscular, 164, 172 Intraperitoneal, 72, 75, 164, 165 Intraperitoneal chemotherapy, 72, 165 Intravenous, 4, 7, 23, 28, 164, 165, 172 Invasive, 13, 165, 176 Involuntary, 159, 165, 169 Ionizing, 142, 156, 165, 178 Ions, 145, 155, 162, 165 Irinotecan, 4, 7, 8, 32, 50, 55, 57, 76, 78, 80, 84, 91, 92, 116, 165 Irradiation, 11, 31, 111, 165, 186 J Jaundice, 56, 162, 165 K Kb, 124, 165 Keratolytic, 165, 174 Ketoconazole, 61, 108, 165 Kinetics, 38, 165 L Lacrimal, 55, 65, 165 Large Intestine, 151, 154, 164, 165, 178, 180 Latent, 38, 165 Leiomyosarcoma, 25, 165 Lesion, 11, 165, 166 Letrozole, 6, 165 Leucovorin, 8, 165 Leukemia, 50, 55, 84, 89, 102, 155, 160, 166 Ligament, 166, 176 Lipid, 148, 160, 166 Liposomal, 14, 41, 51, 72, 76, 166 Liposome, 10, 57, 166 Liver, 141, 145, 147, 150, 153, 154, 159, 161, 162, 166 Local therapy, 10, 166 Localization, 85, 163, 166 Localized, 19, 31, 43, 55, 77, 156, 164, 166, 174 Locomotion, 166, 174 Lupus, 59, 166 Lymph, 73, 149, 156, 166, 182 Lymph node, 73, 149, 166 Lymphatic, 164, 166, 167, 180 Lymphatic system, 166, 180 Lymphocytes, 70, 143, 162, 163, 166, 186 Lymphocytic, 15, 166
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Lymphoid, 143, 152, 166 Lymphoma, 14, 79, 166 Lysine, 112, 166 M Malignancy, 17, 166 Malignant, 13, 28, 57, 79, 102, 111, 141, 143, 166, 167, 168, 169, 170, 176, 178, 179 Malignant mesothelioma, 167, 168 Malignant tumor, 167, 169 Mammary, 167, 182 Mammography, 112, 167 Matrix metalloproteinase, 52, 145, 167 Maximum Tolerated Dose, 14, 155, 167 Medical oncologist, 13, 167 Medicament, 111, 167 MEDLINE, 125, 167 Melanin, 167, 173, 185 Melanocytes, 167 Melanoma, 37, 57, 101, 102, 111, 112, 167 Membrane, 5, 149, 151, 152, 158, 167, 169, 171, 173, 174, 175, 184 Membrane Lipids, 167, 173 Meninges, 149, 167 Mercury, 159, 167 Mesenchymal, 156, 167 Mesentery, 167, 173 Mesothelioma, 28, 167, 168 Metabolite, 5, 146, 147, 165, 168, 175 Metastasis, 7, 21, 27, 73, 87, 96, 167, 168 Metastatic, 6, 8, 14, 17, 21, 22, 24, 25, 28, 29, 30, 32, 34, 35, 36, 37, 40, 41, 42, 43, 44, 47, 48, 49, 50, 51, 52, 55, 56, 57, 60, 62, 63, 65, 67, 68, 69, 71, 72, 75, 77, 78, 79, 80, 81, 83, 85, 86, 87, 89, 90, 91, 96, 101, 102, 109, 112, 116, 117, 168, 179 Metastatic cancer, 109, 168 Methanol, 109, 168 Methotrexate, 5, 27, 34, 168 Microbe, 168, 183 Microorganism, 168, 186 Microtubules, 11, 16, 17, 96, 98, 102, 149, 168, 172 Miscible, 109, 168, 173 Mitomycin, 44, 168 Mitosis, 99, 100, 102, 104, 143, 144, 168 Mitotic, 11, 100, 155, 157, 168, 182, 186 Mitotic inhibitors, 155, 168, 182 Mitoxantrone, 41, 53, 54, 57, 110, 168 Mobilization, 29, 40, 42, 168 Modification, 109, 168, 177
Molecular, 4, 9, 11, 12, 14, 27, 36, 42, 58, 68, 69, 73, 106, 125, 127, 146, 152, 159, 168, 183, 184 Molecule, 16, 143, 145, 148, 150, 151, 153, 158, 161, 162, 168, 171, 178, 185 Monitor, 5, 10, 35, 169, 170 Monoclonal, 7, 8, 14, 47, 145, 162, 165, 169, 177, 184, 186 Monocytes, 19, 164, 169, 182 Mononuclear, 6, 169, 184 Monotherapy, 29, 54, 84, 169 Morphological, 5, 155, 167, 169 Morphology, 38, 169 Motility, 19, 163, 169, 180 Mucins, 156, 161, 169, 179 Mucosa, 156, 166, 169 Mucositis, 7, 47, 169, 183 Multicenter study, 90, 169 Multiple Myeloma, 89, 169 Myelosuppression, 169, 186 Myocardium, 42, 169 N Nasal Cavity, 169 Nasal Mucosa, 65, 169 Nausea, 143, 155, 169 NCI, 1, 9, 123, 150, 169 Necrolysis, 38, 169 Necrosis, 144, 169 Neoadjuvant Therapy, 15, 32, 50, 62, 71, 170 Neoplasia, 21, 170, 176 Neoplasm, 98, 170, 179, 185 Nervous System, 149, 170, 182, 185 Neuropathy, 70, 170, 173 Neurotoxicity, 170, 186 Neurotransmitter, 144, 160, 162, 170, 182 Neutral Glycosphingolipids, 149, 170 Neutrons, 142, 165, 170, 177 Neutrophil, 68, 170 Nitrogen, 96, 105, 142, 153, 157, 158, 170 Normal Distribution, 6, 170 Nuclear, 6, 147, 152, 155, 158, 159, 170, 176 Nuclei, 142, 152, 155, 160, 168, 170, 177 Nucleic acid, 163, 170 Nucleus, 107, 110, 144, 145, 149, 153, 154, 156, 158, 159, 166, 169, 170, 171, 176, 177, 181 O Ointments, 155, 171 Oncogene, 14, 83, 171 Oncologist, 32, 64, 65, 81, 167, 171 Oncolysis, 171
193
Oncolytic, 103, 171 Oophorectomy, 171, 182 Orchiectomy, 171, 182 Organ Specificity, 5, 171 Organ Transplantation, 153, 171 Organelles, 149, 153, 167, 169, 171 Oropharynx, 83, 171 Osteoporosis, 147, 171 Ovaries, 144, 157, 171, 182 Overall survival, 7, 171 Oxaliplatin, 48, 171 Oxidation, 105, 141, 144, 146, 153, 171 Oxidation-Reduction, 146, 171 P P53 gene, 44, 172 Palliative, 43, 172, 183 Pancreas, 9, 25, 61, 141, 146, 154, 172, 184 Pancreatic, 9, 12, 50, 51, 61, 79, 83, 157, 172 Pancreatic cancer, 9, 12, 50, 51, 61, 79, 83, 157, 172 Paneth Cells, 156, 172 Parathyroid, 147, 172 Parathyroid hormone, 147, 172 Parenteral, 34, 97, 172 Parietal, 172, 173, 174 Partial response, 102, 172 Particle, 166, 172, 184 Pathologic, 144, 146, 162, 172, 178, 185 Pathologic Processes, 144, 172 Peer Review, 9, 39, 172 Pelvic, 172, 176 Pelvis, 147, 165, 171, 172, 185 Peptide, 172, 174, 175, 176 Perennial, 172, 184 Perfusion, 173, 183 Perineal, 173, 177 Perioperative, 10, 173 Peripheral blood, 19, 29, 40, 42, 81, 164, 173 Peripheral Neuropathy, 77, 173 Peritoneal, 50, 63, 72, 164, 173 Peritoneal Cavity, 164, 173 Peritoneum, 76, 147, 167, 173 Pharmaceutical Preparations, 101, 112, 157, 173 Pharmaceutical Solutions, 155, 173 Pharmacodynamic, 42, 173 Pharmacokinetic, 4, 6, 17, 37, 40, 42, 61, 64, 65, 68, 74, 75, 76, 173 Pharmacologic, 145, 173, 183 Pharynx, 169, 171, 173 Phenotype, 15, 36, 145, 173
Phenyl, 96, 173 Phenylalanine, 173, 185 Phospholipids, 97, 158, 167, 173 Phosphorus, 147, 173, 174 Phosphorylated, 19, 150, 174 Phosphorylates, 30, 174 Phosphorylation, 15, 38, 88, 154, 174 Physiologic, 142, 174, 178 Physiology, 141, 145, 174 Pigment, 167, 174 Pilot study, 9, 40, 42, 54, 73, 90, 174 Plants, 111, 144, 148, 160, 169, 174, 183, 184, 185 Plaque, 23, 174 Plasma, 20, 35, 36, 52, 143, 149, 150, 159, 161, 169, 174, 180, 183 Plasma cells, 143, 169, 174 Plasmapheresis, 73, 174 Platelet-Derived Growth Factor, 57, 174 Platelets, 169, 174 Platinum Compounds, 171, 174 Pleura, 174 Pleural, 28, 174 Pneumonia, 152, 174 Pneumonitis, 27, 36, 58, 85, 89, 174 Podophyllotoxin, 102, 157, 174 Polyethylene, 101, 175 Polymorphism, 92, 175 Polypeptide, 150, 156, 159, 175 Polyposis, 151, 175 Polysaccharide, 143, 175 Posterior, 172, 175 Postnatal, 175, 181 Potentiates, 4, 9, 19, 30, 175 Potentiating, 110, 175 Practice Guidelines, 126, 175 Precancerous, 158, 175 Preclinical, 10, 18, 44, 175 Precursor, 97, 101, 102, 110, 111, 153, 156, 161, 173, 175, 176, 185 Premalignant, 175, 176 Preoperative, 82, 88, 175 Prodrug, 175 Prognostic factor, 53, 175 Progression, 7, 16, 18, 34, 52, 104, 143, 175, 184 Progressive, 21, 38, 149, 150, 155, 157, 169, 175, 185 Progressive disease, 38, 175 Promoter, 16, 175 Prone, 107, 176 Prophase, 103, 176
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Prostaglandins, 163, 176 Prostaglandins A, 163, 176 Prostatectomy, 19, 55, 176, 177 Prostate-Specific Antigen, 34, 176 Prostatic Intraepithelial Neoplasia, 19, 176 Prostatic Neoplasms, 157, 176 Protease, 151, 176, 179 Protein Binding, 176, 183 Protein S, 146, 176 Proteins, 12, 56, 142, 143, 146, 148, 149, 150, 151, 158, 167, 169, 170, 172, 174, 176, 177, 180 Proteinuria, 169, 176 Proteolytic, 151, 159, 176 Protocol, 17, 88, 176 Protons, 142, 162, 165, 177 Proto-Oncogene Proteins, 172, 177 Proto-Oncogene Proteins c-mos, 172, 177 Pseudomembranous Colitis, 56, 177 Psychiatric, 145, 177 Public Policy, 125, 177 Publishing, 20, 177 Pulmonary, 83, 87, 146, 177 Pulse, 169, 177 Q Quality of Health Care, 172, 177, 184 Quality of Life, 7, 177, 182 R Race, 8, 177 Radiation Oncology, 4, 5, 75, 83, 177 Radiation therapy, 4, 58, 77, 78, 141, 158, 164, 165, 170, 177, 178, 179, 186 Radical prostatectomy, 31, 55, 177 Radioactive, 147, 162, 163, 164, 165, 170, 177, 178, 186 Radioimmunotherapy, 177, 178 Radiolabeled, 101, 165, 177, 178, 186 Radiology, 177, 178 Radiosensitization, 10, 178 Radiotherapy, 7, 41, 44, 58, 61, 64, 71, 83, 84, 89, 147, 165, 177, 178, 186 Randomized, 7, 34, 35, 42, 44, 51, 52, 55, 60, 81, 83, 84, 85, 155, 178 Reagent, 98, 178 Receptor, 4, 10, 15, 16, 19, 57, 141, 143, 161, 178, 180 Recombinant, 14, 101, 178, 185 Recombination, 152, 160, 178 Rectum, 144, 150, 151, 154, 160, 165, 176, 178 Recurrence, 87, 150, 178 Reductase, 10, 144, 168, 178
Refer, 1, 147, 151, 162, 166, 170, 178, 183 Refractory, 8, 19, 29, 50, 51, 58, 61, 65, 66, 73, 76, 77, 79, 80, 90, 98, 99, 103, 178 Regimen, 9, 13, 15, 21, 53, 55, 60, 62, 89, 92, 155, 178 Remission, 178 Renal pelvis, 178, 184 Resorption, 147, 178 Respiration, 148, 169, 178 Respiratory failure, 22, 179 Response rate, 7, 179 Retropubic, 176, 177, 179 Retropubic prostatectomy, 177, 179 Retrospective, 35, 52, 85, 179 Retroviral vector, 160, 179 Rheumatoid, 101, 112, 179 Rheumatoid arthritis, 101, 112, 179 Ribonucleoside Diphosphate Reductase, 162, 179 Ribose, 179, 183 Rigidity, 174, 179 Risk factor, 87, 156, 179 Ritonavir, 28, 179 S Saline, 103, 110, 179 Saliva, 179 Salivary, 40, 154, 172, 179, 182 Salvage Therapy, 62, 179 Sarcoma, 72, 110, 179 Screening, 5, 89, 112, 150, 179 Secondary tumor, 168, 179 Secretion, 150, 156, 162, 169, 179, 180 Secretory, 176, 179 Sedimentation, 179, 184 Selective estrogen receptor modulator, 180, 182 Semen, 176, 180 Semisynthetic, 17, 104, 107, 147, 157, 180 Sequencing, 76, 180 Sequential treatment, 72, 180 Serine, 176, 177, 180 Serotonin, 161, 170, 180 Serum, 4, 19, 56, 151, 180, 184 Side effect, 15, 38, 55, 96, 100, 119, 141, 146, 153, 155, 169, 180, 182, 183, 186 Single-agent, 35, 180 Skeletal, 16, 169, 180 Skeleton, 147, 180 Skin graft, 180, 181 Small cell lung cancer, 25, 31, 32, 33, 35, 41, 42, 45, 48, 49, 53, 54, 58, 62, 63, 65,
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67, 68, 71, 72, 78, 79, 85, 90, 92, 101, 102, 112, 115, 170, 180 Small intestine, 5, 155, 162, 164, 180, 186 Social Environment, 177, 180 Sodium, 33, 110, 180 Solid tumor, 10, 12, 13, 14, 30, 32, 37, 42, 49, 75, 76, 98, 102, 103, 143, 145, 155, 180 Solvent, 157, 160, 168, 173, 180 Somatic, 168, 173, 180, 181 Somatic cells, 168, 181 Species, 42, 97, 150, 157, 168, 169, 171, 177, 181, 182, 184, 186 Specificity, 5, 141, 181, 183 Spectrum, 165, 181 Sperm, 181, 182, 184 Spinal cord, 149, 167, 170, 181 Squamous, 10, 30, 31, 34, 35, 36, 37, 44, 54, 62, 63, 64, 74, 157, 170, 181, 186 Squamous cell carcinoma, 10, 31, 34, 44, 54, 63, 64, 74, 157, 170, 181, 186 Squamous cells, 181 Stem Cells, 29, 42, 81, 181 Stenosis, 67, 181 Stents, 101, 112, 181 Sterility, 153, 181 Steroids, 152, 160, 181 Stomach, 116, 141, 148, 154, 157, 160, 162, 169, 173, 180, 181 Stool, 150, 165, 181 Strand, 11, 181 Stress, 169, 179, 181 Stricture, 181 Subacute, 59, 164, 182 Subcutaneous, 41, 44, 172, 182 Submaxillary, 156, 182 Subspecies, 181, 182 Substance P, 168, 179, 182 Supportive care, 41, 83, 182 Suppression, 73, 182 Suramin, 8, 182 Surgical castration, 6, 182 Survival Rate, 10, 111, 171, 182 Symphysis, 176, 182 Symptomatic, 83, 90, 182 Synergistic, 6, 44, 71, 72, 101, 103, 110, 182 Systemic, 16, 28, 82, 106, 120, 146, 157, 164, 165, 177, 182, 186 Systemic therapy, 82, 182 T Tamoxifen, 6, 8, 180, 182 Taxanes, 4, 13, 15, 17, 18, 96, 97, 98, 104, 106, 107, 108, 109, 182
Testicles, 171, 182 Testosterone, 178, 182 Thalidomide, 71, 83, 182 Therapeutics, 7, 9, 27, 42, 44, 56, 66, 68, 69, 73, 81, 83, 120, 183 Thoracic, 44, 45, 77, 78, 84, 154, 174, 183 Thrombin, 159, 183 Thrombocytopenia, 87, 183 Thromboembolism, 71, 183 Thymidine, 6, 40, 183 Thymidine Phosphorylase, 6, 40, 183 Thymidylate Synthase, 6, 17, 183 Thyroid, 40, 172, 183, 185 Tissue Distribution, 75, 183 Tolerance, 41, 87, 141, 183 Tonicity, 161, 183 Topical, 7, 157, 183 Topoisomerase inhibitors, 142, 165, 183 Topotecan, 42, 76, 78, 183 Toxic, iv, 15, 38, 42, 96, 103, 142, 152, 153, 154, 156, 168, 170, 174, 183 Toxicity, 5, 6, 7, 8, 10, 14, 17, 24, 38, 42, 64, 66, 68, 83, 87, 91, 92, 103, 148, 155, 167, 183 Toxicology, 126, 183 Toxin, 183 Transduction, 10, 184 Transfection, 146, 160, 184 Transfusion, 161, 184 Transitional cell carcinoma, 63, 184 Translating, 9, 184 Translational, 4, 7, 184 Transurethral, 176, 184 Transurethral resection, 176, 184 Transurethral Resection of Prostate, 176, 184 Trastuzumab, 7, 26, 43, 47, 51, 62, 75, 79, 85, 86, 89, 116, 184 Treatment Failure, 106, 184 Trees, 97, 184 Trypanosomiasis, 182, 184 Tuberculosis, 166, 184 Tubulin, 17, 82, 88, 98, 99, 103, 104, 168, 184 Tumor marker, 146, 184 Tumor model, 4, 13, 19, 58, 68, 184 Tumor Necrosis Factor, 182, 184 Tumor suppressor gene, 172, 185 Tumor-derived, 19, 185 Tumour, 41, 111, 144, 171, 185 Tyrosine, 4, 185
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U Unresectable, 22, 25, 43, 64, 78, 185 Uracil, 17, 185 Urethra, 176, 184, 185 Uridine Diphosphate, 92, 185 Urinary, 176, 179, 185 Urinary tract, 185 Urine, 146, 150, 156, 176, 178, 185 Urothelium, 80, 185 Uterus, 147, 149, 156, 165, 171, 185 V Vaccine, 141, 176, 185 Vascular, 18, 66, 142, 164, 185 Vasodilation, 142, 185 Vector, 11, 184, 185 Vegetative, 146, 185 Vein, 165, 170, 185 Venous, 28, 71, 78, 176, 185 Venous Thrombosis, 28, 185 Venules, 146, 147, 185 Veterinary Medicine, 125, 185 Villus, 5, 186 Vinblastine, 15, 44, 184, 186
Vinca Alkaloids, 15, 186 Vincristine, 184, 186 Vindesine, 81, 186 Vinorelbine, 15, 22, 23, 32, 35, 40, 53, 54, 55, 56, 57, 61, 62, 69, 79, 85, 89, 90, 186 Viral, 10, 184, 186 Virulence, 144, 183, 186 Virus, 68, 154, 161, 164, 174, 179, 184, 186 Visceral, 173, 186 Vitro, 4, 5, 13, 19, 186 Vivo, 4, 5, 10, 12, 13, 16, 19, 54, 186 W Warts, 174, 186 White blood cell, 143, 159, 161, 166, 169, 170, 174, 186 Wound Healing, 10, 167, 186 X Xenograft, 10, 12, 30, 88, 143, 184, 186 X-ray, 159, 165, 170, 177, 178, 186 X-ray therapy, 165, 186 Y Yeasts, 173, 186
