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Book-47206.Pdf ffirs.qxd 1/24/07 9:18 AM Page i The Cancer Treatment Revolution ffirs.qxd 1/24/07 9:18 AM Page ii ffirs.qxd 1/24/07 9:18 AM Page iii The Cancer Treatment Revolution How Smart Drugs and Other New Therapies Are Renewing Our Hope and Changing the Face of Medicine David G. Nathan John Wiley & Sons, Inc. ffirs.qxd 1/24/07 9:18 AM Page iv Copyright © 2007 by David G. Nathan. All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada Wiley Bicentennial Logo: Richard J. Pacifico No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 646-8600, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permissions. The information contained in this book is not intended to serve as a replacement for professional medical advice. Any use of the information in this book is at the reader’s discretion. The author and the publisher specifically disclaim any and all liability arising directly or indirectly from the use or application of any information contained in this book. A health care professional should be consulted regarding your specific situation. For general information about our other products and services, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. For more information about Wiley products, visit our web site at www.wiley.com. Library of Congress Cataloging-in-Publication Data: Nathan, David G., date. The cancer treatment revolution : how smart drugs and other new therapies are renewing our hope and changing the face of medicine / David G. Nathan. p. cm. Includes bibliographical references and index. ISBN 978-0-471-94654-0 (cloth) 1. Cancer—Patients. 2. Cancer—Treatment—Popular works. I. Title. RC263.N38 2007 616.99Ј4—dc22 2006024621 Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 ffirs.qxd 1/24/07 9:18 AM Page v To Jean and the wonderful family she gave me ffirs.qxd 1/24/07 9:18 AM Page vi ftoc.qxd 1/24/07 9:18 AM Page vii Contents Acknowledgments ix Prologue 1 Introduction: The Nature of the Beast 7 Mario’s Story ONE: The First Hours 23 TWO: The Plan 31 THREE: Leukemia and Cancer Chemotherapy 38 FOUR: The Final Treatment Plan for Mario 68 FIVE: The Risk of Chemotherapy Resistance 75 SIX: Three Critical Smart Drugs: Nursing Care, Psychology, and Social Work 83 SEVEN: Mario’s Future 89 Joan’s Story EIGHT: A Pleasant Summer Day 99 NINE: Bad News 103 TEN: An Initial Plan 110 ELEVEN: The Surgical Plan 118 TWELVE: The Medical Plan 133 THIRTEEN: The Baton Is Passed 138 FOURTEEN: The Consequences of Therapy 143 FIFTEEN: The Future of Epithelial Cancer Therapy 155 vii ftoc.qxd 1/24/07 9:18 AM Page viii viii CONTENTS Ken’s Story SIXTEEN: The Explosion 163 SEVENTEEN: Cancerous Hens and Constipated Mice 172 EIGHTEEN: Triumph and Tragedy 186 NINETEEN: The Search for More Smart Drugs 203 Glossary 217 Bibliography 237 Index 255 flast.qxd 1/24/07 9:18 AM Page ix Acknowledgments I am in debt to the many supporters and colleagues who made this book possible. From the beginning of the project, I received the encourage- ment, wisdom, and skill of my wonderful agent, Jill Kneerim, and of the president of the Dana-Farber Cancer Institute, Edward J. Benz, Jr., M.D. Initial editing advice came from Steven Marcus. Laura Van Dam became my private editor during the final year of completion of the manuscript. She did a masterful job even while battling her own serious illness. The manuscript was ultimately dissected and improved by Tom Miller, Juliet Grames, and Kimberly Monroe-Hill at Wiley. The construction of this book required over a score of transcribed interviews with patients and with colleagues who have contributed far more to cancer care and research than I. These and other significant editing expenses were defrayed by generous grants from the Richard and Susan Smith Family Foundation and the Goldhirsh Foundation. The first draft of the book was assembled during a delightful five- week residence at the Villa Serbelloni of the Rockefeller Foundation in Bellagio, Italy, in the fall of 2003. I am grateful to the foundation and to colleagues who supported my application for the residency. These were Joseph Goldstein, M.D., Phillip Sharp, Ph.D., and Harold Varmus, M.D. Several colleagues, family members, and friends willingly read sec- tions of this book and gave me excellent critiques. They included Ann Barnet, M.D., the late Richard J. Barnet, Nathaniel I. Berlin, M.D., Sis- sela and Derek Bok, Thomas Brand, Deborah Charness, George Demetri, M.D., Mimi Dow, Frank H. Gardner, M.D., Judy Holding, Philip Kantoff, M.D., Steven Karp, David Livingston, M.D., Robert Mayer, M.D., Linda Nathan, C. O. North, Ann Partridge, M.D., Orah Platt, M.D., Kornelia Polyak, M.D., Ph.D., Dorothy Puhy, and Jane Weeks, M.D. I have tried to incorporate their suggestions and thank them for their efforts. I am particularly thankful to Samuel J. Cohen for his contributions to the suggested reading list and to David E. Fisher, M.D., ix flast.qxd 1/24/07 9:18 AM Page x x ACKNOWLEDGMENTS and Loren Walensky, M.D., who scanned parts of the manuscript for sci- entific accuracy. If errors remain, they are mine. The practical task of assembly of this book fell in order to Janet Cam- eron, Toby Church, Bernadine B. Kirkland, and Cathy Lantigua. With- out their combined effort, the manuscript would still be in tatters. My wonderful wife, Jean F. Nathan, devoted hour after hour to por- ing over chapters, forcing rewrites, and asking all the right questions. For this and fifty-five years of helping me in every possible way, I thank her from the bottom of my heart. Finally, I want to thank the caretakers, cancer researchers, and patients who inspired this book and made it possible. I have vaguely wanted to write about “smart” drugs in cancer for several years. But the story would be as dull as a textbook were it not about real patients and about the physicians, nurses, basic scientists, and support staff who sur- round them. Mario’s family, Joan, and Ken were particularly generous of their time. They did so because they, like the clinicians, nurses, staff members, and researchers, want to help others through the strait gate of cancer. Having suffered, they hope to relieve suffering for others. It is an honor to share their stories and the stories of their caretakers and cancer researchers with my readers. cprol.qxd 1/24/07 1:27 PM Page 1 Prologue en nearly died one night in 1999. He was forty-eight years old and K had been treated repeatedly with blood transfusions for unex- plained anemia, but never for a minute did he think he was close to death. He was working every day and enjoying life. Then came the night all hell broke loose. He awoke suddenly with terrible abdominal pain and went into shock. If fast-moving EMTs and a savvy surgeon at his community hospital had not realized that Ken required immediate abdominal surgery, he would not have survived the night. The operation revealed a grapefruit-size tumor attached to his small intestine. Some of the tumor cells had grown into his bowel, leaving a huge hole in his intestine. That night, the contents of Ken’s gut had poured into his abdomen and caused terrible inflammation and shock. Worse, the tumor cells had scattered all over his belly. He was doomed to have multiple cancers grow in his abdomen. A few weeks later, Ken and his wife, Peggy, learned he had a form of cancer that would result in an utterly unmanageable situation when the distributed tumor cells began to grow. He had no traditional treatment options, since the cancer—gastrointestinal stromal tumor, most often called GIST—stubbornly resists radiation and chemotherapy. And its complete surgical removal was impossible. But Peggy did not give up hope. She went on the Internet and found that George Demetri, an oncologist at the Dana-Farber Cancer Institute in Boston, was just a few months away from starting a clinical trial with the first so-called smart drug treatment for tumors like Ken’s. One of the leading physicians interested in GIST, Demetri had learned that a mutation in a single gene in one of the billions of cells in an otherwise healthy body causes the disease. The altered gene, called an oncogene, creates proteins that figuratively shout at cells to divide con- stantly—that is, to become cancerous. The oncologist also found out that the pharmaceutical company Novartis had developed a drug that should be able to halt the mutated gene’s actions by blocking the shouting pro- tein’s function, thus killing the cancer.
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