Physicians’ Cancer Chemotherapy Drug Manual 2015 Other Jones & Bartlett Learning Oncology Titles Breast Cancer Treatment by Focused Microwave Thermotherapy, Fenn Cancer in Children and Adolescents, Carroll/Finlay Contemporary Issues in Breast Cancer: A Nursing Perspective, 2e, Hassey Dow Dx/Rx: Brain Tumors, Quant Dx/Rx: Breast Cancer, 2e, Lake Dx/Rx: Cervical Cancer, 2e, Robison/Dizon Dx/Rx: Colorectal Cancer, Holen/Chung Dx/Rx: Genitourinary Oncology: Cancer of the Kidney, Bladder, and Testis, 2e, Galsky Dx/Rx: Gynecologic Cancer, Dizon/Campos Dx/Rx: Head and Neck Cancer, Hu et al Dx/Rx: Liver Cancer, Abou-Alfa/Ang Dx/Rx: Lung Cancer, 2e, Azzoli Dx/Rx: Leukemia, 2e, Burke Dx/Rx: Lymphoma, Persky Dx/Rx: Melanoma, Carvajal Dx/Rx: Palliative Cancer Care, Malhotra/Moryl Dx/Rx: Pancreatic Cancer, Lowery/O’Reilly Dx/Rx: Prostate Cancer, 2e, Kampel Dx/Rx: Upper Gastrointestinal Malignancies: Cancers of the Stomach and Esophagus, Shah Genomic and Molecular Neuro-Oncology, Zhang/Fuller Glioblastoma Multiforme, Markert et al Gynecologic Tumor Board: Clinical Cases in Diagnosis and Management of Cancer of the Female Reproductive System, Dizon/Abu-Rustum Handbook of Breast Cancer Risk-Assessment, Vogel/Bevers Handbook of Cancer Emergencies, Marinella Handbook of Cancer Risk Assessment and Prevention, Colditz/Stein Handbook of Radiation Oncology: Basic Principles and Clinical Protocols, Haffty/ Wilson How Cancer Works, Sompayrac Management of Nausea and Vomiting in Cancer and Cancer Treatment, Hesketh Medical and Psychosocial Care of the Care Survivor, Miller Molecular Oncology of Breast Cancer, Ross/Hortobagyi Molecular Oncology of Prostate Cancer, Ross/Foster Pancreatic Cancer, Von Hoff/Evans/Hruban Pediatric Stem Cell Transplantation, Mehta Pocket Guide to Chemotherapy Protocols, 7e, Chu Tarascon Pocket Oncologica, Marinella The Cancer Book, Cooper The Hospital for Sick Children Handbook of Supportive Care in Pediatric Oncology, Abla The Johns Hopkins Breast Cancer Handbook for Health Care Professionals, Shockney/ Tsangaris For a complete list of our oncology titles, see www.jblearning.com/medicine/oncology Physicians’ Cancer Chemotherapy Drug Manual 2015 Edward Chu, MD Professor of Medicine and Pharmacology & Chemical Biology Chief, Division of Hematology-Oncology Deputy Director University of Pittsburgh Cancer Institute University of Pittsburgh School of Medicine Pittsburgh, PA Vincent T DeVita, Jr., MD Amy and Joseph Perella Professor of Medicine Professor of Epidemiology and Public Health Yale University School of Medicine New Haven, CT World Headquarters Jones & Bartlett Learning Wall Street Burlington, MA 01803 978-443-5000 info@jblearning.com www.jblearning.com Jones & Bartlett Learning books and products are available through most bookstores and online booksellers To contact Jones & Bartlett Learning directly, call 800-832-0034, fax 978-443-8000, or visit our website, www.jblearning.com Substantial discounts on bulk quantities of Jones & Bartlett Learning publications are available to corporations, professional associations, and other qualified organizations For details and specific discount information, contact the special sales department at Jones & Bartlett Learning via the above contact information or send an email to specialsales@jblearning.com Copyright © 2015 by Jones & Bartlett Learning, LLC, an Ascend Learning Company ISBN: 978-1-284-07521-2 All rights reserved No part of the material protected by this copyright notice may be reproduced or utilized in any form, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without written permission from the copyright owner The content, statements, views, and opinions herein are the sole expression of the respective authors and not that of Jones & Bartlett Learning, LLC Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not constitute or imply its endorsement or recommendation by Jones & Bartlett Learning, LLC and such reference shall not be used for advertising or product endorsement purposes All trademarks displayed are the trademarks of the parties noted herein Physicians’ Cancer Chemotherapy Drug Manual 2015 is an independent publication and has not been authorized, sponsored, or otherwise approved by the owners of the trademarks or service marks referenced in this product There may be images in this book that feature models; these models not necessarily endorse, represent, or participate in the activities represented in the images Any screenshots in this product are for educational and instructive purposes only Any individuals and scenarios featured in the case studies throughout this product may be real or fictitious, but are used for instructional purposes only The authors, editor, and publisher have made every effort to provide accurate information However, they are not responsible for errors, omissions, or for any outcomes related to the use of the contents of this book and take no responsibility for the use of the products and procedures described Treatments and side effects described in this book may not be applicable to all people; likewise, some people may require a dose or experience a side effect that is not described herein Drugs and medical devices are discussed that may have limited availability controlled by the Food and Drug Administration (FDA) for use only in a research study or clinical trial Research, clinical practice, and government regulations often change the accepted standard in this field When consideration is being given to use of any drug in the clinical setting, the health care provider or reader is responsible for determining FDA status of the drug, reading the package insert, and reviewing prescribing information for the most up-to-date recommendations on dose, precautions, and contraindications, and determining the appropriate usage for the product This is especially important in the case of drugs that are new or seldom used Production Credits Executive Editor: Nancy Anastasi Duffy Senior Production Editor: Dan Stone Director of Special Markets: Eileen Ward V.P., Design and Production: Anne Spencer Rights and Photo Research Coordinator: Ashley Dos Santos Manufacturing and Inventory Control Supervisor: Amy Bacus Composition: Cenveo Publisher Services Cover Image: © xrender/Shutterstock Cover Design: Kristin E Parker Printing and Binding: Edward Brothers Malloy Cover Printing: Edward Brothers Malloy 6048 Printed in the United States of America 10 18 17 16 15 14 Contents Editors and Contributing Authors vi Preface vii Acknowledgments viii Chapter Chapter Principles of Cancer Chemotherapy Introduction The Role of Chemotherapy in the Treatment of Cancer Principles of Combination Chemotherapy Chemotherapeutic and Biologic Drugs Chapter 3 Guidelines for Chemotherapy and Dosing Modifications 467 Chapter 4 Common Chemotherapy Regimens in Clinical Practice 487 Chapter 5 Antiemetic Agents for the Treatment of Chemotherapy-Induced Nausea and Vomiting 625 Index 665 v Editors Edward Chu, MD Professor of Medicine and Pharmacology & Chemical Biology Chief, Division of Hematology-Oncology Deputy Director University of Pittsburgh Cancer Institute University of Pittsburgh School of Medicine Pittsburgh, PA Vincent T DeVita, Jr., MD Amy and Joseph Perella Professor of Medicine Professor of Epidemiology and Public Health Yale University School of Medicine New Haven, CT Contributing Authors M Sitki Copur, MD Ryan Ramaekers, MD Adjunct Professor of Medicine University of Nebraska Medical Director, Saint Francis Cancer Center Grand Island, NE Adjunct Assistant Professor of Medicine University of Nebraska Saint Francis Cancer Center Grand Island, NE Laurie J Harrold, MD Clinical Nurse Specialist Hematology-Oncology Associates Meriden, CT Dawn E Tiedemann, AOCN, APRN Medical Oncologist Pittsburgh, PA vi Preface The development of effective drugs for the treatment of cancer represents a significant achievement beginning with the discovery of the antimetabolites and alkylating agents in the 1940’s and 1950’s The success of that effort can be attributed in large measure to the close collaboration and interaction between basic scientists, synthetic organic chemists, pharmacologists, and clinicians This tradition continues to flourish, especially as we now enter the world of pharmacogenomics, genomics, and proteomics, and the rapid identification of new molecular targets for drug design and development In this, our 15th edition, we have condensed and summarized a wealth of information on chemotherapeutic and biologic agents in current clinical practice into a reference guide that presents essential information in a practical and readable format The primary indications, drug doses and schedules, toxicities, and special considerations for each agent have been expanded and revised to take into account new information that has been gathered over the past year We have also included six new agents that have all been approved by the FDA within the past year This drug manual is divided into five chapters Chapter gives a brief overview of the key principles of cancer chemotherapy and reviews the clinical settings where chemotherapy is used Chapter reviews individual chemotherapeutic and biologic agents that are in current clinical use; these agents are presented in alphabetical order according to their generic name In this chapter, specific details are provided regarding drug classification and category, key mechanisms of action and resistance, critical aspects of clinical pharmacology and pharmacokinetics, clinical indications, special precautions and considerations, and toxicity Chapter includes recommendations for dose modifications that are required in the setting of myelosuppression and/or liver and renal dysfunction Relevant information is also provided highlighting the teratogenic potential of various agents Chapter presents a review of the combination drug regimens and selected single-agent regimens for solid tumors and hematologic malignancies that are used commonly in daily clinical practice This section is organized alphabetically by specific cancer type Finally, Chapter reviews commonly used antimetic agents and individual agents used to treat chemotherapy-induced nausea and vomiting, which is a significant toxicity observed with many of the anticancer agents in current practice Our hope remains for this book to continue to serve as both an in-depth reference and an immediate source of practical information that can be used by physicians and other healthcare professionals actively involved in the daily care of cancer patients This drug manual continues to be a work in progress, and our goal is to continue to update it on an annual basis and to incorporate new drugs and treatment strategies that reflect the ongoing advances in the field of cancer drug development Edward Chu, MD Vincent T DeVita, Jr., MD vii Acknowledgments This book represents the efforts of many dedicated people It reflects my own personal and professional roots in the field of cancer pharmacology and cancer drug development It also reaffirms the teaching and support of my colleagues and mentors at Brown University, the National Cancer Institute (NCI), and the Yale Cancer Center In particular, Bruce Chabner, Paul Calabresi, Robert Parks, Joseph Bertino, and Vince DeVita have had a major influence on my development as a cancer pharmacologist and medical oncologist While at the NCI, I was fortunate to have been trained under the careful tutelage of Carmen Allegra, Bob Wittes, and Bruce Chabner At Yale, I was privileged to work with a group of extraordinarily talented individuals including Yung-chi Cheng, William Prusoff, Alan Sartorelli, and Vince DeVita, all of whom have graciously shared their scientific insights, wisdom, support, and friendship I would also like to take this opportunity to thank my co-author, colleague, mentor, and friend, Vince DeVita, who recruited me to the Yale Cancer Center and who has been so tremendously supportive of my professional and personal career Special thanks go to my colleagues at Jones & Bartlett Learning for giving me the opportunity to develop this book and for their continued encouragement, support, and patience throughout this entire process I wish to thank my wife, Laurie Harrold, for her love and patience, for her insights as a practicing medical oncologist, and for her help in writing and reviewing various sections of this book I would also like to thank my parents, Ming and Shih-Hsi Chu, for their constant love, support, and encouragement, and for instilling in me the desire, joy, and commitment to become a medical oncologist and cancer pharmacologist Finally, this book is dedicated to my faithful dogs, Mika and Lexi, and to my two beautiful children, Ashley and Joshua, who have brought me great joy and pride and who have shown me the true meaning of unconditional loyalty and love Edward Chu, MD viii Principles of Cancer Chemotherapy Vincent T DeVita, Jr and Edward Chu Introduction The development of chemotherapy in the 1950’s and 1960’s resulted in curative therapeutic strategies for patients with hematologic malignancies and several types of advanced solid tumors These advances confirmed the principle that chemotherapy could indeed cure cancer and provided the rationale for integrating chemotherapy into combined-modality programs with surgery and radiation therapy in early stages of disease to provide clinical benefit Since its early days, the principal obstacles to the clinical efficacy of chemotherapy have been toxicity to the normal tissues of the body and the development of cellular drug resistance The development and application of molecular techniques to analyze gene expression of normal and malignant cells at the level of DNA, RNA, and/or protein has greatly facilitated the identification of some of the critical mechanisms through which chemotherapy exerts its antitumor effects and activates the program of cell death This modern-day technology now includes next-generation sequencing, whole-exome sequencing, and whole-genome sequencing, and these advances have provided important new insights into the molecular and genetic events within cancer cells that can confer chemosensitivity to drug treatment as well as having identified potential new therapeutic targets This enhanced understanding of the molecular pathways by which chemotherapy and targeted therapies exert their antitumor activity, and by which genetic alterations can result in resistance to drug therapy, has provided the rationale for developing innovative therapeutic strategies Principles of Cancer Chemotherapy Table Emetogenic Potential of Chemotherapy Agents Level Frequency of Emesis (%) >90 AC regimen (doxorubicin plus â•… cyclophosphamide) Agent Actinomycin-D Altretamine Carmustine 250 mg/m2 Cisplatin $50 mg/m2 Cyclophosphamide 1500 mg/m2 Dacarbazine 500 mg/m2 Ifosfamide $2 g/m2 Mechlorethamine Pentostatin Procarbazine Streptozocin 60–90 Carboplatin Carmustine 250 mg/m2 Cisplatin ,50 mg/m2 Cyclophosphamide 750–1500 mg/m2 Cytarabine 1000 mg/m2 Doxorubicin 60 mg/m2 Irinotecan Melphalan (IV) Methotrexate 1000 mg/m2 Aldesleukin 12–15 million IU/m2 30–60 Arsenic trioxide Azacitidine Cyclophosphamide #750 mg/m2 Cyclophosphamide (oral) Cytarabine 200 mg/m2 Doxorubicin 20–60 mg/m2 Epirubicin #90 mg/m2 660 Physicians’ Cancer Chemotherapy Drug Manual Table (cont.) Level Frequency of Emesis (%) Agent 30–60 5-Fluorouracil 1000 mg/m2 Idarubicin Ifosfamide Imatinib Methotrexate 250–1000 mg/m2 Mitoxantrone ,15 mg/m2 Temozolomide 10–30 Albumin-bound paclitaxel Aldesleukin ,12 million IU/m2 Bexarotene Capecitabine Cetuximab Cytarabine 100–200 mg/m2 Daunorubicin Docetaxel Doxorubicin ,20 mg/m2 Etoposide 5-Fluorouracil ,1000 mg/m2 Gemcitabine Liposomal doxorubicin Lomustine Methotrexate 50–250 mg/m2 Mitomycin-C Paclitaxel Pemetrexed Thiotepa Topotecan Vorinostat [...]... intermittent palliative chemotherapy showed that a policy of stopping and rechallenging with the same chemotherapy provides a reasonable treatment option for patients Similar observations have been observed in the treatment of metastatic disease of other tumor types, including NSCLC, breast cancer, germ cell cancer, ovarian cancer, and small cell lung cancer 4 Physicians Cancer Chemotherapy Drug Manual 2 Chemotherapeutic... anal cancer, gastroesophageal cancer, laryngeal cancer, and non–small cell lung cancer, optimal clinical benefit is derived when chemotherapy is administered with radiation therapy, either concurrently or sequentially One of the most important roles for cancer chemotherapy is in conjunction with local treatment modalities such as surgery and/or radiation therapy; this has been termed adjuvant chemotherapy. .. refers to the use of chemotherapy for patients who present with localized cancer for which alternative local therapies, such as surgery, exist but are less than completely effective At present, neoadjuvant therapy is most often administered in the treatment of anal cancer, bladder cancer, breast cancer, esophageal cancer, laryngeal cancer, locally advanced non–small cell lung cancer (NSCLC), and osteogenic... decreases to 7 hours with chronic treatment, suggesting that the drug may accelerate its own rate of degradation 26 Physicians Cancer Chemotherapy Drug Manual Indications 1 Breast cancer Hormone-responsive, advanced disease 2 Prostate cancer Hormone-responsive, advanced disease A Dosage Range Usual dose is 250 mg PO qid (1000 mg total) Drug Interaction 1 Warfarin, phenytoin, phenobarbital, theophylline,... chemotherapy regimens with clinical activity against advanced disease may have curative potential following surgical resection of the primary tumor, provided the appropriate dose and schedule are administered It is now well-established that adjuvant chemotherapy is effective in prolonging both disease-free 2 Physicians Cancer Chemotherapy Drug Manual survival (DFS) and OS in patients with breast cancer, ... castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel Dosage Range Recommended dose is 1000 mg PO once daily in combination with prednisone 5 mg PO bid Drug Interactions • Use with caution in the presence of CYP2D6 substrates • Use with caution in the presence of CYP3A4 inhibitors and inducers 6 Physicians Cancer Chemotherapy Drug Manual Special Considerations... Toxicity 6 Neurotoxicity with peripheral sensory neuropathy Toxicity 7 Asthenia, fatigue, and pyrexia 10 Physicians Cancer Chemotherapy Drug Manual Afatinib COOH F COOH CI NH N N A COOH COOH H N O N O CH2 CH2 O Trade Names Gilotrif Classification Signal transduction inhibitor Category Chemotherapy drug Drug Manufacturer Boehringer Ingelheim Mechanism of Action • Potent and selective small-molecule inhibitor... thrombocytopenia also observed In rare instances, pancytopenia with marrow hypoplasia occurs, which can be fatal 22 Physicians Cancer Chemotherapy Drug Manual Altretamine A Trade Names Hexalen, Hexamethylmelamine, HMM Classification Nonclassic alkylating agent Category Chemotherapy drug Drug Manufacturer MGI Pharma Mechanism of Action • Triazine derivative that requires biochemical activation in the... new drug therapeutic regimens First, only drugs known to be partially effective against the same tumor when used alone should be selected for use in combination If available, drugs that produce some fraction of complete remission are preferred to those that produce only partial responses Second, when several drugs of a class are available and are equally effective, a drug should Principles of Cancer Chemotherapy. .. for 3 years as opposed to 1 year Principles of Combination Chemotherapy With rare exceptions (e.g., choriocarcinoma and Burkitt’s lymphoma), single drugs at clinically tolerable doses have been unable to cure cancer In the 1960s and early 1970s, drug combination regimens were developed based on known biochemical actions of available anticancer drugs rather than on their clinical efficacy Such regimens