The following essay by Paul A. Bunn, Jr, MD, is adapted from The Big Casino: America’s Best Cancer Doctors Share Their Most Powerful Stories, which was coedited by Stan Winokur, MD, and Vincent Coppola and published in May 2014. The book is available on Amazon.com and thebigcasino.org.
I grew up in upstate New York. I was heavily influenced to become a physician by my parents and my high school sweetheart, who later became my wife. My father, an infectious disease physician, developed tuberculosis while he was at medical school, as did most of his classmates. He dedicated his life to the elimination of tuberculosis as a medical scourge worldwide and was largely successful. Ironically, he died at a young age in part due to his generation’s smoking habits, bad diet, and lack of physical activity.
Medical Training Amid the Vietnam War
I graduated from Amherst College in Massachusetts with a major in biology. My mentors were most interested in teaching students how to think. I attended Weill Cornell Medical College in New York City but was disappointed my first 2 years there because the emphasis seemed to be on how to memorize information rather than how to think. However, my second 2 years there were much more rewarding. I was exposed to unbelievable clinicians such as Rees Prichard, MD, and Martin Gardy, MD, who taught me how to put patients first, and scientists such as Walter Riker, MD, who taught me many of the principles of medical research.
My medical training took place in the 1960s, and with the Vietnam War raging, nearly every medical student was being drafted and sent to fight the war, which is what happened to my cousin who was also studying to become an internist. He developed tuberculosis while stationed on a military ship and told me that unless I wanted to become a surgeon, it might be best to avoid being drafted.
Early Research Leads to Today’s Successes
After my medical residency, like thousands of other students, I applied to the National Institutes of Health (NIH) for a fellowship and was accepted into the Leukemia Branch of the National Cancer Institute (NCI). During my internship at the University of California, San Francisco, I was assigned to the NCI’s Pediatric Branch. Since I was most interested in adult medicine, I was reassigned to the Medicine Branch. During my residency, many of the early combination chemotherapy regimens for lymphoma, adult leukemia, and breast cancer were starting to show improved outcomes in patients.
The fact that these men and women would choose to spend 6 weeks in a hospital under treatment with the most toxic of chemotherapies is a testament to their strength and hope.— Paul A. Bunn, Jr, MD
Because the NIH Clinical Center was not a complete hospital, physicians had to perform their own blood draws on patients; start IVs; and complete all treatment procedures, including biopsies, laparoscopies, and even dialysis. By the end of my fellowship, the NCI had decided to dedicate one of its branches to lung cancer, which was the leading cause of cancer death then and still is. The Lung Cancer Branch was located at the Washington, DC, Veterans Affairs Medical Center because of the large number of patients with lung cancer in treatment.
At the time, treatment for lung cancer was very unsatisfactory. Back then, very little was known about lung cancer biology, and nothing was known about the molecular biology or molecular pathogenesis of the disease. Several drugs had shown activity in small cell lung cancer, but each had considerable toxic side effects and complete remissions were rare. To address the issues of biology and molecular biology, the group attempted to establish cell lines from every patient biopsy.
They were called human tumor cell lines and were numbered sequentially. Much of what we know of lung cancer biology and molecular biology today originated from these lines. Some of our earliest observations were that the cell lines produced their own growth factors and had frequent losses of portions of human chromosomes and tumor-suppressor genes. They expressed antigens to which monoclonal antibodies could be produced.
Drugs that inhibited cell-line growth frequently produced responses in patients with lung cancer. Cell lines could be grown in laboratory mice to test new therapies in vivo. Our initial trials in small cell lung cancer included a three-drug chemotherapy regimen of cyclophosphamide, methotrexate, and lomustine. Unfortunately, the treatment was so toxic that all the patients developed severe neutropenia and were hospitalized for a minimum of 6 weeks. The fact that these men and women would choose to spend 6 weeks in a hospital under treatment with the most toxic of chemotherapies is a testament to their strength and hope.
Dispelling the Stigma of Smoking and Lung Cancer
Years later, I was recruited to the University of Colorado School of Medicine in Denver, where I continued my lung cancer studies. One of my early patients was a physician (and never smoked) who had bilateral lung metastases but was asymptomatic. Convinced that chemotherapy could only decrease his quality of life, he elected to avoid any therapy. I followed him for 11 years, observing his slowly progressive nodules. When he became symptomatic, he agreed to be treated with platinum-based chemotherapy. He suffered considerable toxicity and some response but died within a year.
This doctor/patient relationship taught me that our goal as oncologists is to prolong both the duration and quality of life of patients, which is something patients decide with support from their physicians. This patient’s case also illustrated the variability in outcomes, our inability to predict an outcome, and the importance of scientific research in making advances in cancer.
At the time, there was an odd perception that patients with lung cancer were somehow morally suspect—tobacco addicts or worse—rather than victims of a devastating disease. When this patient presented with lung cancer, the prevailing view had not changed: lung cancer was associated with the stigma of guilt associated with tobacco, and treatments were solely unscientific poisons.
The past decade has changed this view. We have witnessed profound new possibilities in treatment advancements in this disease with molecularly tailored therapies and checkpoint immune inhibitors. These new therapies are providing much higher response rates and much longer responses than earlier chemotherapies, and they do so with considerably less toxicity than cytotoxic chemotherapy.
It’s now clear that patients should have their tumors tested for the presence of molecular drivers and biomarkers associated with improved outcomes. These therapies are providing new hope and meaningful prolongation of life with more acceptable toxicity. The promise that rational combinations of these therapies may further improve patient outcomes and lead to some cures justifies the long periods of work.
And, yes, hope. ■
Dr. Bunn is Distinguished Professor in the Division of Medical Oncology and James Dudley Chair in Lung Cancer Research at the University of Colorado School of Medicine in Denver.