November 12 , 2004

Study of cancer trials finds significant safety improvement

The chance that patients in early-stage cancer research studies will die from the experimental treatments has dropped dramatically over the past decade, according to a MGH study in the Nov. 3 Journal of the American Medical Association. An analysis of more than 200 Phase 1 research trials from 1991 through 2002 showed that treatment-related deaths decreased by 90 percent during the study period. "Now we can tell patients with cancer that, compared with 10 years ago, they can expect a higher level of safety when they enroll in early-stage clinical trials." says Thomas Roberts Jr., MD, of the MGH Cancer Center and the paper's lead author.

Representing the first time potential new drugs are tested in humans, Phase 1 trials have a goal of assuring drug safety and determining the best dosage. Since there had been no comprehensive safety analysis of Phase 1 cancer trials since the mid-1980s, while concerns about safety had risen, the researchers compiled a database of trials that included approximately 6,500 patients and analyzed information on deaths, toxic effects and whether treatment caused tumors to shrink. The most significant change during the study period was the dramatic drop in the risk of drug-related deaths. The chance that tested drugs would have a measurable anti-tumor effect also dropped but by only 50 percent, suggesting a possible improvement in the overall risk/benefit ratio.

The researchers note that safety improvements could result from increased attention to regulations, the use of less-toxic targeted therapies and improvements in supportive care. Because targeted therapies may stop tumor growth without measurable shrinkage, new ways of evaluating success may be required, says Roberts. His MGH co-authors are Bernardo Goulart, MD, Bruce Chabner, MD, Jeffrey Clark, MD, Elkan Halpern, PhD, and G. Scott Gazelle, MD, MPH, PhD.