Reflections on the Evolution of Clinical Cancer Research and Turning Points in a Distinguished Career

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If you get standard treatment for an invariably fatal malignancy, you die. If you have experimental therapy, you have a chance to live. Research matters; it saves lives.

— Karen H. Antman, MD

Since May 1, 2005, Karen H. Antman, MD, has served as Dean of Boston University School of Medicine and Provost of the Boston University Medical Campus, located in the historic South End of Boston. Her road to this esteemed institution was paved with prominent positions, such as former ASCO President, and high honors, notably ASCO’s Distinguished Award for Scientific Leadership. Even more important than her positions and honors are Dr. Antman’s achievements as a clinical investigator, which have moved the field of oncology forward.

Early Experiences

Dr. Antman has always enjoyed people and science. While an undergraduate at Muhlenberg College in Allentown, Pennsylvania, she knew two patients with cancer who had markedly different outcomes, which demonstrated to her the possibilities held by science and set her on the path to a career in oncology. A neighbor developed leukemia and was told that it was incurable. “He was dead a year later, exactly as his doctors predicted,” said Dr. Antman. The following year, a classmate was diagnosed with advanced Hodgkin lymphoma and was also given a fatal prognosis. However, when Dr. Antman showed up for class the following September, to her surprise, there he was. “A fellow student asked, ‘What are you doing here?’ He said he’d been at the NIH on a clinical protocol of combination chemotherapy and he was doing very well, thanks for asking,” said Dr. Antman.

Oncology was already high on Dr. Antman’s list of possible specialties as she prepared to enter Columbia University’s College of Physicians and Surgeons. After completing internal medicine residencies at Columbia, Dr. Antman and her husband headed to Boston, where she was accepted for an oncology fellowship at Dana-Farber Cancer Institute, staying on as faculty.

Experiential knowledge is a compelling tool in a doctor’s bag. Dr. Antman noted that the take-home experience from her early college years—seeing a neighbor succumb to cancer and a classmate survive—was fortified during her fellowship at Dana-Farber as she watched many of her patients in the clinic die. “If you get standard treatment for an invariably fatal malignancy, you die. If you have experimental therapy, you have a chance to live. Research matters; it saves lives.”

Pioneer in Sarcoma Research

Prior to her Deanship at Boston University School of Medicine, Dr. Antman was President of the American Association for Cancer Research. In her Presidential address, she observed, “Sarcoma, long a no man’s land for cancer researchers, is slowly giving up its secrets.” Fittingly, it was Dr. Antman who led some of the early research in sarcoma’s “no man’s land” to uncover these secrets. In the 1980s, advanced sarcomas were treated with doxorubicin, which in phase II trials did not prolong survival. Dr. Antman’s European colleagues shared evidence about a new ifosfamide derivative showing activity in sarcomas. “But the agent sparked little enthusiasm in the United States,” she recalled. “For obvious reasons, Pharma isn’t particularly interested in uncommon tumors.”

Undeterred, Dr. Antman did the paperwork herself and filed the investigational new drug (IND) application with the FDA. “I remember when the drug first arrived from Europe; the custom’s agent called me and asked, ‘What is this stuff?’ I explained that it was an investigational new cancer drug for a clinical trial,” said Dr. Antman. However, despite the European evidence of activity, some patients on Dr. Antman’s seminal sarcoma study were refused hospitalization coverage, which raised bothersome questions about access to clinical trial research.

“I remember a 24-year-old patient who was denied coverage because ifosfamide was deemed experimental. I argued to the insurance company that the Europeans reported that it was twice as effective as cyclophosphamide, which is covered. They replied, ‘We don’t tell you what drug to prescribe, we just won’t cover it.’ So the Dana-Farber Cancer Institute, to its credit, covered the costs for that patient’s hospitalization,” said Dr. Antman.

Ifosfamide was indeed active in sarcomas, and Dr. Antman’s team studied the drug in a combination regimen that became standard for these malignancies. When the drug was found to be effective in both sarcomas and testicular cancer, the FDA finally took notice and cross-filed on Dr. Antman’s IND.

Streamlining Clinical Trial Regulations

The young patient’s ordeal became a turning point in Dr. Antman’s medical career. “That specific patient gave me pause, and I made a decision to do patient advocacy. My team and I wrote an article in The New England Journal of Medicine on the crisis in clinical research, and we testified before Congress and at various subcommittees on the Hill about the crucial need to cover patients on clinical trials.”

Dr. Antman noted that besides coverage, the clinical trial process itself posed an impediment to access. In 2004, she served as Deputy Director for Translational and Clinical Sciences at the National Cancer Institute (NCI). During her time at NCI, Dr. Antman recalled long meetings with multiple federal agencies, seeking ways to streamline the cumbersome clinical trial regulations. Her frustration was echoed during a conversation with another past ASCO President, Emil “Tom” Frei III, MD. “Tom said that we never would have cured childhood leukemia if we had today’s regulations. I have repeated that powerful quote over and over to junior faculty,” said Dr. Antman.

Teaching the Next Generation

In a career as demanding as cancer care, where every success is tempered by the knowledge that this deadly disease still holds its share of secrets, what keeps the professional fire burning? As Dean of Boston University School of Medicine, Dr. Antman is driven by her involvement in medical education and efforts to enhance the research and infrastructure capabilities on campus. She also teaches first-, second-, and fourth-year students, giving cancer lectures. “I’m still very engaged in teaching oncology to medical students,” she said.

Dr. Antman was recently voted into the Institute of Medicine, another major recognition for her achievements in medicine. Along with her challenging duties at Boston University School of Medicine, she is on the board of a number of prominent international organizations that foster worldwide medical education. Leading a life so robust in advancing the causes of oncology, Dr. Antman spends her time out of work on the simple pleasures, such as hiking with her grandchildren.

Why Oncology?

Regarding the impending workforce shortage in oncology, Dr. Antman said, “I would urge young physicians to choose oncology because it is a field in which they can truly make a difference in the world, in research and in the clinic. To the public, scientific advances seem to come at a snail’s pace, but in actuality we have made incredible progress. When I was a second-year medical student and the pathology lecture turned to testicular cancer, the men in the class uniformly cringed. At that time it was about 90% fatal; now, the same disease is about 90% curable. And that progress happened rather rapidly,” she added.

“Being part of the research and clinical possibilities in such a dreaded disease is certainly a compelling reason for a medical student to choose oncology. And in a broader sense, oncology can serve as a model for the future of our health-care system. For decades, oncology has been what the system-at-large needs: a multidisciplinary, team-based care approach for individual patients.” ■

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