The Patient as Research Partner

Victoria Stern, MA


March 24, 2015

In This Article

The Outsize Impact of a Single Patient

One afternoon almost 40 years ago, Richard L. Schilsky, MD, received a call from a patient. The patient was in a clinical trial investigating the efficacy of a new drug, cisplatin, to treat ovarian cancer and she was experiencing something odd. She couldn't stop shaking.

Dr Schilsky, then a fellow in oncology at the National Cancer Institute (NCI), asked her to come in to the clinic immediately.

"Because she was on an investigational chemotherapy drug, my first thought was she was shivering because she had a bad bacterial infection," said Dr Schilsky, now the chief medical officer of the American Society of Clinical Oncology (ASCO). "But after undergoing a series of tests, it turned out that her blood counts were normal and she had no signs of infection or fever."

As she underwent further testing, Dr Schilsky realized she wasn't shaking. She was twitching uncontrollably.

"It turned out she had a profoundly low level of magnesium in her blood and had diffuse muscle twitching," he said. "She was the first case ever reported of hypomagnesaemia due to cisplatin."

In a subsequent research paper,[1] Dr Schilsky defined this complication for the first time. Now, hypomagnesaemia is a well-recognized side effect of cisplatin and patients who receive the drug get a magnesium supplement.

"It's hardly ever a problem anymore, but back then when we didn't know everything we needed to know about the drug, if this patient hadn't called in and reported her symptom, it might have been some time before the problem was ever discovered," Dr Schilsky said.

The ways in which individual patients respond to drugs in the clinical trial setting can offer invaluable clues to treating cancer, especially patients who have had remarkable responses.

In a recent trial of women with ovarian cancer, George Coukos, MD, PhD, recalls a patient who had a particularly amazing response to a new immunotherapy drug. When Dr Coukos and his colleagues examined her more closely, they discovered that among patients in her cohort, she was the only one treating her pain with heavy doses of nonsteroidal anti-inflammatory drugs (NSAIDs).

"After this initial observation, we realized there may be an important synergy between the immunotherapy and NSAIDs," said Dr Coukos, head of the Department of Oncology at the University of Lausanne, and director of the Ludwig Center UNIL for cancer research (Lausanne, Switzerland).

This observation fueled studies in mice, one of which was recently published in Nature Medicine,[2] and a clinical trial at the University of Pennsylvania that combines vaccine therapy with aspirin.

"One patient's incredible response launched a novel line of research," said Dr Coukos.

On the other hand, Michael Postow, MD, has also seen how patients with poor responses can encourage new insights into treating cancer. Dr Postow and his mentor, Jedd Wolchok, MD, recently treated a patient with melanoma with the new immunotherapy agent ipilimumab (Yervoy®), but he was not improving. They then decided to give him a combination of radiation therapy and ipilimumab. His tumors began to shrink.

"This one patient spurred a whole new field of investigation into the efficacy of combining ipilimumab with radiation therapy, which has now led to a number of clinical trials," said Dr Postow, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City.


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