Vincent T. DeVita, Jr, Helped Usher in the Era of Chemotherapy, Turning Lethal Cancers Into Curable Ones


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Vincent T. DeVita, Jr, MD

There is no better reward than seeing patients who have lived more than 40 years who might have died. It is a great feeling and one of the benefits of growing older.

—Vincent T. DeVita, Jr, MD

Although Vincent T. DeVita, Jr, MD, harbored fantasies as a young child of becoming an ice deliveryman when he grew up, his love of chemistry and biology, as well as admonitions from his mother, Isabel, “to become a doctor,” propelled him toward a career in medicine. Now, more than 6 decades later, Dr. DeVita’s contributions to the science of cancer are heralded as leading to some of the most significant breakthroughs in the progress against the disease since President Richard Nixon launched the “War on Cancer” in 1971.

Born on March 7, 1935, in the Bronx, New York, Dr. DeVita studied chemistry and biology at the College of William and Mary, a school he choose partly to honor his maternal grandfather, Ernest LoNano, a master antique restorer, who restored Colonial Williamsburg in Williamsburg, Virginia, where the college is located, to its historic form. While there, he met Mary Kay Bush, whom he married soon after their graduation in 1957.

The couple then moved to Washington, DC, where Dr. DeVita attended George Washington University School of Medicine. A couple of years into his studies, Dr. DeVita was invited by his physiology professor to spend the summer at Mount Desert Island Biological Laboratory in Bar Harbor, Maine. While there, he met David P. Rall, MD, PhD, then Chief of Chemical Pharmacology at the National Cancer Institute (NCI), who offered Dr. DeVita a job.

“I had done extremely well in my pharmacology course in medical school and when I received my national board grades, Dr. Rall asked me to come to the NCI, where I could also fulfill my national service time,” said Dr. DeVita. “The Vietnam War was going on then, and working at the NCI counted as time spent in military service and allowed me to avoid the draft. It was a coveted position, and I took advantage of it.”

Dr. DeVita would spend the majority of his medical career in various positions at the NCI, including Senior Investigator, Head of the Solid Tumor Service, Chief of the Medical Branch, Director of the Division of Cancer Treatment, Clinical Director, and then Director of the NCI from 1980 to 1988.

Although cardiology was Dr. DeVita’s initial choice as a medical specialty during his residency, when he saw the investigations being done in cancer drug development at the NCI, he switched his focus to oncology and “was hooked.” During his first year there, Dr. DeVita became interested in Hodgkin lymphoma. His investigation of the disease would come to dominate his early research efforts and lead to the era of curative chemotherapy in oncology care.

Proving Chemotherapy Is a Viable Cancer Therapy

In the early- to mid-1960s, the field of cancer therapy centered on its two top weapons, surgery and radiation, despite the fact that neither was effective against stopping the systemic spread of solid tumors or halting the progression in blood cancers like leukemia. The result was cure rates stuck at a dismal 33%.

Then, in 1965, after mouse studies by Howard Skipper, PhD, a mathematical biologist at the Southern Research Institute in Birmingham, Alabama, produced the first curative treatment of a mouse leukemia using combination chemotherapy, Dr. DeVita and his colleagues at the NCI began researching combination chemotherapies in the treatment of Hodgkin lymphoma, a then fatal disease, often treated with single alkylating agents.

First, they developed the MOMP protocol, which combined nitrogen mustard, vincristine, methotrexate, and prednisone, followed by the MOPP protocol, which omitted methotrexate and added procarbazine, a drug Dr. DeVita had been studying. Initially derided within the National Institutes of Health Clinical Center as too big a departure from the norm, MOPP began showing impressive results in early clinical trials.

In a study of MOPP in 188 patients with advanced Hodgkin lymphoma, the complete remission rate went from 0% to 80%. The remission rates were so unheard of and such a testament to the feasibility of curing cancer with drugs, data from the MOMP and MOPP studies were presented at meetings of the American Association for Cancer Research (AACR) in 1965 and 1967, respectively. In 1970, the final results from the MOPP study were published in the Annals of Internal Medicine.1

“We didn’t have a lot of molecular tools in those days, so we designed the protocol based on the growth characteristics of the mouse and human bone marrow and assumptions about the growth kinetics of human tumors and what we knew of the mechanism actions of the drugs,” said Dr. DeVita. “We had to translate the data from mice to humans based on the limits of their growth characteristics, so it was a clever design for the time, and it worked. The principles used in the MOPP program have become part of the protocols used in chemotherapy drug combinations ever since.”

Attaining Remarkable Remissions

In 44 years of follow-up studies of the original 188 patients in the MOPP study, 60% of the patients who attained a complete remission have remained cancer-free, and only one patient developed a secondary leukemia. “If patients are treated with MOPP alone, they don’t have a high risk of developing secondary tumors,” said Dr. DeVita. “It’s when you add radiotherapy to the treatment that patients develop second tumors mostly in the radiation field.”

The importance of the MOPP discovery, said Dr. DeVita, was not just that it was successful in curing Hodgkin lymphoma—today, cure rates for this disease top 90%—but that the treatment proved advanced cancer in major organ systems in adults could be cured using drugs. “There is no better reward than seeing patients who have lived more than 40 years who might have died. It is a great feeling and one of the benefits of growing older,” said Dr. DeVita.

In 1972, Dr. DeVita received the Albert Lasker Clinical Medical Research Award for his pioneering work in the development of combination chemotherapy in the treatment of Hodgkin lymphoma. And, in September 2014, ASCO named the MOPP protocol among the Top 5 Advances in 50 Years of Modern Oncology.

From Triumph to Tragedy

The success of MOPP marked a turning point in Dr. DeVita’s career, resulting in an appointment as Head of NCI’s Solid Tumor Service in 1968, followed 3 years later by a promotion to Chief of its Medicine Branch. But a year later, in 1972, personal tragedy struck when Dr. DeVita’s son, Ted, just 9 at the time, developed the lethal and rare bone marrow disorder aplastic anemia.

Ted was taken to a laminar airflow room at the NCI clinic in Bethesda, Maryland, where he lived for 8 years until his death in 1980. “The area outside Ted’s room became our living room,” said Dr. DeVita. The family, including Ted’s younger sister, Elizabeth, and his mother, Mary Kay, would visit every day, with Dr. DeVita often staying until late at night teaching Ted to play the guitar and chess. After Ted went to sleep, Dr. DeVita retreated to his lab to pursue his research.

It was during this time that Dr. DeVita, in collaboration with George Canellos, MD, developed the protocol for CMF (cyclophosphamide, methotrexate, and fluorouracil) in the adjuvant setting for breast cancer. The protocol has since contributed to a significant decline in breast cancer mortality, establishing another major accomplishment in cancer advancement.

“Work was a great escape for me, but it was a very difficult time,” said Dr. DeVita. “Mary Kay bore the brunt of caring for Ted and Elizabeth. She is a very strong woman.”

The heartbreak of losing a young child served to make Dr. DeVita an even more compassionate physician and cemented his determination to find cures for life-threatening diseases. “Losing Ted had a big effect on me,” said Dr. DeVita. “When I started in the field, I took care of young kids with leukemia, and there is no more trying experience than watching little kids go through cancer and its treatment. In those days, most of them died, so I had seen the devastation firsthand. I thought I knew what those parents were going through and when I had to go through it, I found it to be even worse than I thought. I became a little more dedicated in trying to solve this problem. If I needed motivation, and I didn’t need much, losing Ted gave me more.”

The Power of Music

If medicine is Dr. DeVita’s vocation, opera is his passion, one that he inherited from both his grandfather and his mother, who played opera arias on the piano when he was growing up. It is also his salvation. During the turbulent times of the late 1970s and early 1980s, when expectations for curing cancer were running high and the War on Cancer was faltering, as Director of the NCI and the National Cancer Program, Dr. DeVita became the target of immense criticism.

“Opera became a form of escapism for me,” said Dr. DeVita. “I get involved in the story, and it is a way for me to forget where I am. When I was having difficulty at the NCI with politics and cancer, I would go away for a weekend and see four operas. By the second opera, I would forget all about Washington.”

In Celebration of a Stellar Career

After leaving the NCI in 1988, Dr. DeVita was appointed Physician-in-Chief and Attending Physician at Memorial Sloan Kettering Cancer Center in New York and later served as Director of the Yale Cancer Center from 1993 to 2003. He is currently the Amy and Joseph Perella Professor of Medicine at Yale Cancer Center and Professor of Epidemiology and Public Health at Yale School of Medicine in New Haven, Connecticut.

In acknowledgment of Dr. DeVita’s accomplishments in the advancement of oncology care, he was elected to the European Academy of Sciences in 2002; awarded the Distinguished Medical Science Award, Friends of the National Library of Medicine in 2009; elected President of the American Cancer Society in 2012 and was named an ASCO fellow that same year; and was elected as a fellow of the AACR Academy in 2014.

Dr. DeVita has published more than 450 scientific articles and is the coeditor of Cancer: Principles & Practice of Oncology (Lippincott Williams & Wilkins, 2014), widely regarded as the definitive source of cancer information, now in its 10th edition. He is currently cowriting a book with his daughter Elizabeth ­DeVita-Raeburn, on the history and aftermath of the War on Cancer, the concept of which set unrealistic goals for cure that still haunt the research community today, said Dr. DeVita.

“There are still a lot of people critical about the ‘War on Cancer,’ but the criterion that was imposed, to eradicate all cancer, was impossible to meet. We are never going to eradicate all cancers, but we have been successful in decreasing the overall mortality by 25%, and we are on our way to converting many cancers to chronic diseases. Contrary to what some people think, there has been a lot of measurable progress, but the best is still to come,” said Dr. DeVita. “This is a very, very exciting time in cancer research.” ■

Disclosure: Dr. DeVita reported no potential conflicts of interest.

Reference

1. Devita VT Jr, Serpick AA, Carbone PP: Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Ann Intern Med 73:881-895, 1970.

 



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