Outliving Cancer

PRAISE FOR

Outliving Cancer

Dr. Robert A. Nagourney—Nobel-quality researcher and clinical oncologist, extraordinary physician, and creative maverick—is the doctor I’d go to if I had cancer. For decades, with relentless patience, he’s been proving that many supposedly incurable cancers can be killed, with greatly reduced harm to the patient, simply by using agents preselected in the laboratory to kill those specific cancer cells. His explanation of why this works, and why it’s still misunderstood by many physicians, is a triumph of fact and logic over sloppy assumptions and obsolete habits. Everyone who deals with cancer should read this story, marvel at the results, scrutinize the evidence, and help make the change.

—AMORY B. LOVINS, CHAIRMAN AND CHIEF SCIENTIST, ROCKY MOUNTAIN INSTITUTE

"In Outliving Cancer, Dr. Robert Nagourney brilliantly presents a riveting story of a functional laboratory test that determines the most effective chemotherapy treatment for an individual patient. Everyone’s cancer is different. This chemosensitivity assay determines what will work in you, not in the average person. This book is a must-read for any physician involved in the diagnosis and/or treatment of cancer and for cancer patients and their family members seeking the most effective therapy. Functional laboratory testing rescued my wife from the certain death. Her survival, now almost fourteen years later, was entirely due to Dr. Nagourney’s identification of a drug combination rarely used in ovarian cancer in 1999, and not recommended by any of the seven gynecologic oncologists she consulted. If you have cancer, this book may save your life!"

—THOMAS PANKE, MD, PRESIDENT, SOUTHERN OHIO PATHOLOGY CONSULTANTS, INC.; AUTHOR, PATHOLOGY OF THERMAL INJURY

"Outliving Cancer provides rare insight into the world of a practicing oncologist who is also an innovative research scientist. I highly recommend it to anyone who wants to know why the official war on cancer has progressed so slowly and how it could be made more effective and humane. Dr. Robert Nagourney is a national treasure and in a sane society would be director of the National Cancer Institute."

—RALPH W. MOSS, PHD, AUTHOR, CUSTOMIZED CANCER TREATMENT

"My passion and work for many decades has been in cancer prevention. So it is with great interest that I read Dr. Nagourney’s book, Outliving Cancer. I can see two major advances changing cancer chemotherapy in the next decade: First, we will have personalized testing with individual tumors. Dr. Nagourney is a pioneer in this area, and he tells an interesting story about how he got there and his successes. Second, chemotherapy drugs that only kill tumor cells and have minimal side effects are coming along rapidly. I also see greater understanding and major advances in preventing cancer. Eating a varied diet so that you get your approximately thirty required vitamins and minerals (and, if you are a smoker, giving up smoking) would be a good start on this. In the meantime, we all are grateful to Dr. Nagourney and the other innovators in cancer chemotherapy and cancer prevention."

—BRUCE N. AMES, PHD, SENIOR SCIENTIST, CHILDREN’S HOSPITAL OAKLAND RESEARCH INSTITUTE (CHORI)

"Dr. Nagourney has earned international recognition as the most prominent leader in the field of chemosensitivity testing. A more primitive proliferative assay led many to reject such testing early on. However, Dr. Nagourney’s pioneering work, based on a highly predictive apoptotic assay, has benefitted innumerable cancer patients and played a pivotal role in their treatment outcomes. I believe all patients deserve the quality of information that Dr. Nagourney’s assay provides, and that in the future, oncology practices will routinely incorporate such testing into the optimal care of patients. I encourage everyone concerned with the treatment of cancer to read Outliving Cancer."

—KEITH I. BLOCK, MD, MEDICAL DIRECTOR, BLOCK CENTER FOR INTEGRATIVE CANCER TREATMENT; EDITOR-IN-CHIEF, INTEGRATIVE CANCER THERAPIES, SAGE SCIENCE PRESS; SCIENTIFIC DIRECTOR, INSTITUTE FOR INTEGRATIVE CANCER RESEARCH & EDUCATION; AUTHOR, LIFE OVER CANCER

This diary of an oncology physician-scientist is both educational and enjoyable reading for all those interested in cancer and its treatment.

—PHILIP J. DI SAIA, MD, THE DOROTHY MARSH CHAIR IN REPRODUCTIVE BIOLOGY; PROFESSOR, DEPARTMENT OF OBSTETRICS AND GYNECOLOGY, UNIVERSITY OF CALIFORNIA, IRVINE MEDICAL CENTER

Outliving Cancer

The Better, Smarter Way to Treat Your Cancer

ROBERT A. NAGOURNEY, MD

The information contained in this book is based upon the research and personal and professional experiences of the author. It is not intended as a substitute for consulting with your physician or other healthcare provider. Any attempt to diagnose and treat an illness should be done under the direction of a healthcare professional. The publisher does not advocate the use of any particular healthcare protocol but believes the information in this book should be available to the public. The publisher and author are not responsible for any adverse effects or consequences resulting from the use of the suggestions, preparations, or procedures discussed in this book.

Should the reader have any questions concerning the appropriateness of any procedures or preparation mentioned, the author and the publisher strongly suggest consulting a professional healthcare advisor.

Basic Health Publications, Inc.

28812 Top of the World Drive

Laguna Beach, CA 92651

949-715-7327 • www.basichealthpub.com

Library of Congress Cataloging-in-Publication Data

Nagournery, Robert A.

Outliving cancer / Robert A. Nagourney, MD.

pages cm

Includes bibliographical references and index.

ISBN 978-1-59120-550-0 (alk. paper)

1. Cancer. 2. Oncology. I. Title.

RC261.N25 2012

616.99’4—dc23

2012045669

Copyright © 2013 by Robert A. Nagourney, M.D.

All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the author.

Editor: Carol Killman Rosenberg • www.carolkillmanrosenberg.com Typesetting/Book design: Gary A. Rosenberg • www.thebookcouple.com Cover design: Dann Froehlich Design

Printed in the United States of America

10  9  8  7  6  5  4  3  2  1

Contents

Acknowledgments

Foreword by Keith I. Block, MD

Preface

Introduction

1.  A Walk in the Park

2.  A Brief History of Chemotherapy and Chemosensitivity Testing

3.  Early Scientific Discoveries

4.  Anything That Works

5.  The Neutrino

6.  Epiphany

7.  Cell Death Allows for Life

8.  Unraveling the Mystery

9.  Finally, Rational Therapy

10.  Never Give Cancer an Even Break

11.  Outliving Hospice

12.  East Meets West

13.  Garlic, Wine, Chocolate, and More

14.  Treatable Cancers Should Be Treated Correctly

15.  When All Else Fails

16.  The Progress in Treating Kidney Cancer

17.  Ah, the Simple Life

18.  What to Do When Your Genes Don’t Fit

19.  Genetic Versus Functional Analysis

20.  Targeted Therapies

21.  The Future of Cancer Research Lies Behind Us

22.  The Causes of Cancer

23.  To Cancer and Beyond

APPENDICES

A.  Cancer Research Explained

B.  What to Expect When You’re Expecting a Conversation with Your Oncologist

C.  A Practical Guide for the Use of Chemosensitivity Testing

D.  Assay Criteria

E.  Physician/Patient Advocate Resources

Glossary

References

About the Author

Acknowledgments

I start by thanking Phil Schein, MD, who took me under his wing and guided me through my first experiences with peer-reviewed publications in oncology.

I would also like to thank Larry Weisenthal, MD, PhD, for introducing me to the laboratory technology that has influenced every aspect of my work in oncology.

A very special thanks to Dr. Sheldon Hendler for years of collaboration and brilliant scientific discussion.

Gale (Morrie) Granger for productive collaborations and my introduction to the molecular biology of the human immune system. Kenneth Tew, PhD, who provided me laboratory space and technical support during my fellowship, enabling me to begin my first drug sensitivity lab.

Philip Di Saia, MD, for his support and assistance over the years.

I would like to thank the many surgeons who have collaborated with us to provide tissue samples for our analysis, with particular thanks to Drs. Robert Shuman, Kent Azaren, Imad Shbeeb, Tomi Evans, Anton Bilchik, Peter Dottino, Helmut Schellhas, Sean Cao, Philip Boudreaux, Eugene Woltering, Robert Barone, and Paul Sugarbaker.

I thank Drs. Mel Hoshiko, Joanne Rutgers, Gloria Bertucci, Lowell Rogers, Milton Drachenberg, Julio Ibarra, Steven Romansky, Emanuel Ferro, Joyce King, Lisa Shane, and Savita Ries, as well as all the members of the Long Beach Memorial Medical Center Pathology Department for their expert assistance in processing tissue samples.

Also, my appreciation to my clinical oncology colleagues, Drs. William Lyons, Jonathan Blitzer, Eknath Deo, Nilesh Vora, John Link, Thomas Asciuto, and Steven Lake, as well as my radiation oncology colleagues, Drs. A. M. Nisar Syed, Ajmel A. Puthawala, and Stephen Doggett for their participation and support in our clinical investigations.

I would especially like to thank my laboratory staff, Steven Evans, Paula Bernard, Eric Federico, and all the past members of our group for overseeing the quality of our operations and dedication to our patients. As well as Shari Burt and Robyn LaFrance for their dedication, perseverance, and multiple abilities.

I’d like to thank Marylyn Paulsen, Tonja Smith, and Debbie Fridman for their hard work in our clinical research department and Cathy Kopy for her continued support.

I also want to thank Loretta Stamos, John Stamos, the entire Stamos family, and the dedicated members of the Vanguard Cancer Foundation for helping us to provide our services to those in need.

A special recognition to John Morrison, Michael and Victoria Campbell, Chip Bupp, Marie-Paule Donsimoni, and Anthony Rothchild for their support.

I thank Dietlind Antretter for collaborations and sponsorship of our developmental program.

I would also like to thank Drs. Ralph Moss, Mark Renneker, Keith Block, Thomas Lodi, and Henry Dreher Jr., who steadfastly promoted and defended our work, referred their patients, and collaborated with us to save the lives of numerous patients over the years.

I would like to thank my parents, Alphonse and Barbara, brother Brian, and sister Sarah for everything that families do.

I would like to thank my wife, Maxine, and my sons Alexander and Adam for their love and support before, during, and throughout the preparation of this book.

Finally, I would like to thank every patient I have had the honor of knowing over the years, who has shown such bravery and strength in the face of adversity. Particular thanks go to those patients who kindly allowed us to include their stories in this book.

This book has been a collaboration among myself, Donna Queza, and Carol Beckerman, without whom it would never have come to be. I thank them for their many hours of dedicated effort, editorial expertise, and encouragement. I also thank William Gladstone of Waterside Productions, Inc., and Norman Goldfind of Basic Health Publications, Inc., for believing in this book and shepherding this project through.

Foreword

As an integrative cancer specialist with more than thirty-two years of clinical care experience and having treated over 15,000 cancer patients, I know firsthand that one of the most critical decisions cancer doctors make is determining which chemotherapy regimen is best for a given patient. There are often many options with no clear-cut reason to choose one over another. Occasionally, existing research data may help a doctor lean toward one regimen, but this rarely addresses the individual’s unique biology and tumor characteristics.

Dr. Nagourney’s groundbreaking work has provided an invaluable tool in the task of selecting optimal chemotherapy regimens for patients. His work offers doctors a method to better select drugs that are more likely to work on an individual patient’s cancer, while avoiding unnecessary protocols that may not work as well, and worse, may cause adverse side effects.

Cancer cells are the wily and tough foot soldiers of a disease that starts silently but can disseminate and eventually overwhelm the body. But detached from their surroundings they are powerless and vulnerable. I remember as a medical student carrying petri dishes of cancer cells between laboratories, trying as best I could to keep them from dying. Impressed with the need to transport them carefully, I was astounded by their fragility when separated from the body and their microenvironment. Yet these were the same cells that had killed my uncle, grandfather, and grandmother before I was sixteen. The contrast was instructive. A light bulb went off in my mind as I realized that our bodies have the ability to coddle or combat cancer, depending on the state or condition of this microenvironment.

In Life Over Cancer, I lay out a method for testing and profiling a patient’s microenvironment and methods for tailoring a program to shift this toward a cancer fighting as opposed to a cancer promoting terrain. When it comes to chemotherapy, Dr. Nagourney has taken even further aim at using this environment to get a more accurate assessment to determine the more optimal protocol.

Dr. Nagourney’s recognition of the importance of this microenvironment is a point of distinction of his methodology. His assay, the EVA-PCD® functional profile, is the only method where the potential effectiveness of a drug is evaluated against the cancer cell in the context of its microenvironment—the tumor stroma or matrix, blood vessels, and inflammatory cells. When a tumor sample arrives at the Rational Therapeutics laboratory, it is broken up into microspheroids, fragments that preserve the tumor along with its surroundings. Dr. Nagourney can then test drugs in a situation closer to real-life biology than most chemosensitivity tests, which separates cancer cells from their environment.

Another unique feature of the assay is that this test is based on programmed cell death. Programmed cell death is one of the major ways that cancer drugs eliminate tumors. Early tests for chemosensitivity determined whether drugs stopped cells from proliferating, or rapidly dividing, which was previously thought to be the main way that chemotherapy drugs treated cancers. These chemosensitivity tests lacked accuracy, leading many doctors to reject the concept of chemosensitivity testing. More recent research shows that stimulating programmed cell death, also known as apoptosis, is actually a more important mechanism. In apoptosis, a cancer cell self-destructs at the end of its natural lifespan or after experiencing some type of damage. The EVA-PCD assay determines which drugs best activate apoptosis and actually kill tumor cells, rather than just slow the rate at which they multiply.

Dr. Nagourney’s laboratory also overcomes a limitation of several other current chemosensitivity tests, which can be described as genomic or biomarker tests. These tests are based on correlating genetic markers or mutations found in tumors with the drugs that are typically found effective in patients with these markers. These markers, which include HER-2, BRAF, KRAS, and others, are definitely important for treatment decisions. The problem is that a single tumor may have multiple markers, some known and some that we have yet to recognize. Because the assay actually applies multiple drugs to each patient’s tumor sample, this accounts for the effect of all the markers in the tumor simultaneously.

The potential for improving patients’ outcomes using this technique is powerfully demonstrated in Dr. Nagourney’s October 2012 publication in the journal Anticancer Research. This study tested tumors from thirty-one lung cancer patients at the Rational Therapeutics laboratory. The patients then received the chemotherapy regimens indicated by the functional profile revealed through the assay results. Instead of only a 20 to 30 percent response rate usually seen in lung cancer treatment, nearly 65 percent of these patients had tumor shrinkage or stability. Instead of a typical 9–11 month survival, the average survival of this group was 21.3 months.

This is consistent with what I have experienced with patients using the assay for many years. Some patients have come to us after several regimens of chemotherapy had proven ineffective and they were given no other treatment options. Along with implementing our comprehensive integrative treatment program and chronomodulating chemotherapy—providing drugs in a time-sensitive manner to diminish toxicity while improving response—the findings of the assay provided a direction for treatment that ultimately led to a favorable response.

All cancer patients deserve a comprehensive, individualized, and integrative approach to care. This approach should include therapeutic nutrition; a personalized bio-behavioral, physical care, and fitness program; an individualized nutritional supplement regimen tailored to each patient’s unique disease characteristics; biochemical and molecular profiling; and tailoring for optimal drug regimens. The future of cancer treatment will include making treatment decisions based on each patient’s unique tumor characteristics, and the EVA-PCD assay shows us the way to that future.

The results speak for themselves. If cancer affects you or a loved one, you owe it to yourself to read the fascinating story recounted in Outliving Cancer. As chemosensitivity testing moves onto center stage—and mark my words it will—Dr. Nagourney and his functional profile will be revered. For many, this book will be a gamechanger, or perhaps more aptly, a life-changer! This innovative testing method has helped many of my patients, and it may just provide a genuine solution for you. Please join Dr. Nagourney as he retraces the challenging development of his methodology, and the fruits of his work as seen through the outstanding results experienced by those cancer patients who have used his analyses.

Keith I. Block, MD

Medical Director, Block Center for Integrative Cancer Treatment

Editor-In-Chief, Integrative Cancer Therapies, Sage Science Press

Scientific Director, Institute for Integrative Cancer Research

& Education

Author, Life Over Cancer (Bantam Hardcover)

Preface

As a medical oncology fellow at Georgetown University in the 1980s, I had occasion to attend monthly dinner meetings with guest lecturers from the National Cancer Institute. One evening, Dr. Steven Rosenberg, chief of the surgical branch, came to discuss the management of soft tissue sarcoma. Topics of discussion ranged from the disparities in diagnostic conclusions when pathologists reviewed slides from soft tissue sarcomas (even disagreeing with themselves 25 percent of the time on serial reviews), to the operative management of pulmonary metastases.

What I remember most vividly was Dr. Rosenberg’s description of a young man whose soft tissue sarcoma had recurred multiple times in his lungs. Unwilling to yield, Dr. Rosenberg performed more than a dozen separate thoracotomies (surgical explorations of the lung), cherry-picking lesions each time they appeared. That is, until they stopped appearing.

What Dr. Rosenberg had accomplished surgically was what I decided, then and there, would be my medical raison d’etre. I would labor to someday do with chemotherapeutics what Dr. Rosenberg had done with a scalpel: allow my patients to outlive their cancers. Of course, it would be many years before I had the opportunity to realize this dream, but I never wavered from my goal.

This book describes the scientific rationale for my particular approach to cancer medicine—beginning with an interest in cancer as a disease and my good fortune to work with many accomplished physicians, up to the obstacles I encountered along the way. I also expand upon the profound impact the concept of programmed cell death has had upon my worldview.

The reader will come to understand that cancer is not what it