Cancer: Improving Drug-Radiotherapy Clinical Trials

Several major oncology groups, led by Cedars-Sinai Cancer investigators, have published a white paper in The Lancet Oncology recommending clinical trial designs that can improve testing of new drug-radiotherapy combinations and speed the regulatory approval of these treatments for cancer patients.

Numerous laboratory studies have shown that drug-radiotherapy combinations increase the effectiveness of cancer therapy, but clinical trials in humans have been less successful. Only one new non-chemotherapeutic drug has been approved by the Food and Drug Administration for concurrent treatment with radiation.

“One of the biggest reasons for this is that early-phase clinical trials investigating these combinations are challenging to design and implement,” said Zachary Zumsteg, MD, associate professor of Radiation Oncology and Biomedical Sciences at Cedars-Sinai and first author of the paper. “Since many side effects of radiotherapy occur after treatment is completed, it can take longer to determine the appropriate dose of treatment. Testing of drug-radiation therapy combinations often occurs in patients receiving first-line therapy, leading to less tolerance of unexpected side effects. And because radiotherapy affects each organ differently, new drug-radiotherapy combinations must be tested separately for cancers arising in different parts of the body.”

To address these challenges, investigators suggest designing trials that use mathematical models with real-time toxicity data to calculate appropriate doses for each patient, allowing for continuous patient enrollment and making trials more efficient. They also advocate testing multiple drug-radiotherapy combinations simultaneously to limit the number of patients receiving any specific drug-radiotherapy combination at a given time. They note that these trial designs require substantial infrastructure and expertise, making them best suited for implementation in large cooperative group clinical trial networks.

The authors suggest that if these clinical trial designs are widely adopted, they are more likely to lead to the development of additional safe and effective cancer treatments.

Additional authors: Siddharth Sheth, Salma K Jabbour, Krishnan R Patel, Randall J Kimple, Terence M Williams, Meng Xu-Welliver, Pedro A Torres-Saavedra, Arta M Monjazeb, Jyoti Mayadev, Steven E Finkelstein, John M Buatti, Sandip P Patel, Steven H Lin.

Follow Cedars-Sinai Academic Medicine on LinkedIn for more on the latest basic science and clinical research from Cedars-Sinai.