How a Bold Thinker Helped Introduce Chemotherapy Combinations to Cancer Therapy

Published: Sunday, Dec 21, 2014
Vincent T. DeVita Jr, MD

Vincent T. DeVita Jr, MD

When Vincent T. DeVita Jr, MD, began testing a cocktail of four chemotherapies against advanced Hodgkin disease back in 1964, the disease was uniformly fatal. Many patients were desperate enough to try anything, even a combination of cell-killing poisons that guaranteed them nothing except excruciating pain.

Their gamble paid off with an unimaginable breakthrough, one that DeVita and his colleagues first reported in 1967: The so-called “MOPP” combination (mechlorethamine, Oncovin, procarbazine, and prednisone) produced complete remissions in 80% of patients.

Had DeVita retired the day after he announced those results, he’d still rank among history’s top oncologists, but the 32-year-old doctor was just getting started. Over the next five decades, he has continued to distinguish himself as an innovator with his contributions to cancer research, including developing a treatment protocol that is still used in breast cancer, publishing more than 400 scientific papers, and running the National Cancer Institute (NCI) for nearly 10 years.

Starting on the Research Path

DeVita stumbled into cancer research by accident. “I actually thought I would ultimately go into [private clinical] practice. But then once you’re involved in a major discovery, you’re hooked! From that point on, I was never even tempted to go into practice,” he said.

Born in the Bronx and raised largely in Yonkers, New York, DeVita stood out as a fast-talking Yankee at The College of William and Mary in Virginia, which was still a school with a very Southern culture when he graduated in 1957 with a degree in chemistry. He married shortly thereafter and moved on to medical school at George Washington University in Washington, DC, in 1957.

DeVita conducted some cardiology research during his time there and managed to get several of his studies published. So, when he decided to continue his studies with a fellowship at the National Institutes of Health (NIH), he expected that any position he landed would be in cardiology. He ended up, instead, at the NCI in 1961, just as research into combination chemotherapy was taking off.

More than a decade had passed since Sidney Farber, MD, first demonstrated that a folic acid antagonist could induce remissions in childhood leukemia. Euphoria about chemotherapy’s promise had been replaced with dire pessimism as each new chemical agent to emerge from the labs failed to produce anything more than temporary remissions.

By that point, DeVita said, “Nobody felt you could kill cancer with drugs”—nobody except DeVita’s new colleagues at NCI, who believed that chemotherapies that failed as individual treatments just might cure cancer when used together.

MOPP’s Difficult Beginnings— and Ultimate Success

It is difficult to imagine, now that combination therapy is a cornerstone of cancer treatment, just how controversial this idea was at the time. Nearly the entire medical establishment viewed the “fathers of combination therapy” not only as idiots, but also, thanks to the terrible side effects of their experiments, as sadists to boot. Even colleagues within NCI accused the most aggressive experimenters of running “a butcher’s shop” that performed “cruel and insane” work that should be forbidden outright.

DeVita’s experimental MOPP regimen produced side effects that were extreme even by those standards.

Nausea struck patients with indescribable intensity, while the toxins eradicated their immune systems and made any malady a life-threatening condition.

Among those who survived, most of the men and some of the women were rendered permanently sterile. Some escaped Hodgkin disease only to succumb, about a decade later, to leukemia induced by their treatment.

Nevertheless, DeVita and his colleagues knew almost instantly that they had succeeded beyond anyone’s wildest dreams. Thirty-six of their first 43 patients achieved complete remissions within 6 months of treatment.

The only problem was the name of the new regimen. DeVita called it “Combination 2” until his boss, Emil Frei, III, MD, suggested something catchier. “They’d put together VAMP and BIKE, and because these acronyms were quick, people could remember them,” DeVita said, “But I called it ‘Combination 2.’ And so Frei said, ‘Right. It’s MOPP.’ And it’s been forever MOPP.”

On the Fast Track at NCI

DeVita’s early success at NCI led to rapid promotion. He was appointed head of NCI’s Solid Tumor Service in 1968, chief of its Medicine Branch in 1971, and clinical director for the entire institute in 1975. Each position brought more administrative responsibility, but DeVita managed to find time for prodigious amounts of research throughout those years.

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