Phase I Cancer Trials More Effective Than Thought

Twice as many patients have positive responses to therapies, study finds

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HealthDay Reporter

WEDNESDAY, March 2, 2005 (HealthDay News) -- When patients decide to enter clinical trials using unproven therapies, many do so with a mix of hope and fear.

Now, a new study finds twice as many cancer patients testing medications in these early, phase 1 clinical trials have positive response rates than had been previously believed.

While the response rates varied from zero to nearly 30 percent, depending on the trial, the study found that phase I clinical oncology trials have an overall response rate of 10.6 percent. That means one in 10 study volunteers saw some improvement in their disease.

"There have been, over the last 15 years or so, studies that show the response rates in oncology trials are low, at about 5 percent, and that toxicity is high. There's been debate whether or not it's ethical to have patients in trials where the benefits may be so low," said one of the study's authors, Christine Grady, head of the section on human subjects research in the Department of Clinical Bioethics at the National Institutes of Health.

"We found that the response rates were much higher, [toxicity was lower], and we discovered that the universe of phase I oncology trials is much more diverse than people think it is," said Grady.

Results of the study appear in the March 3 issue of the New England Journal of Medicine.

Phase I clinical trials are designed to assess a drug's proper dosage, and to see how the body metabolizes the medication and what side effects occur. Cancer patients often enroll in phase I trials because no other treatments have been effective against their cancer, and they're desperate to find something that might work.

"Some contend that the enrollment of patients with advanced disease in risk-research studies with little chance of direct benefit exploits a vulnerable population," wrote the study authors.

Grady said that when thinking of phase I trials, most people assume that the trial is on a drug that has never been used in humans before. However, she found that was only the case in about 25 percent of the studies included in her analysis. Many of the trials also included drugs that were already approved by the FDA, but were now being tested in a new combination.

Grady's analysis included all of the non-pediatric phase I oncology trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute between 1991 and 2002. A total of 460 trials with nearly 12,000 participants were included.

The researchers looked for response rates and toxicity in each study. Responses rates were classified into three categories: complete response, which meant the disappearance of a tumor; partial response, which meant a 50 percent reduction in tumor size; stable disease or less-than-partial response.

Rates of complete and partial response went as high as 27 percent in some studies, but the overall response rate was 10.6 percent -- 7.5 percent with a partial response and 3.1 percent with a complete response, the study found.

Out of 11,935 study volunteers, there were 58 deaths believed to be at least possibly related to trial medications -- a rate of 0.49 percent. The highest toxicity -- 0.77 percent -- was reported in trials that combined an investigational medication with an already FDA-approved medication, according to the study.

Grady said the highest death rates still occur in chemotherapy trials.

Dr. Jay Brooks is chairman of hematology and oncology at the Ochsner Clinic Foundation Hospital in Baton Rouge, La. "Probably the most important information for me, as a physician who refers patients to cancer trials, is that the drugs are safe," he said. "We need to know that we're not killing patients with these drugs."

What's exciting, he said, is that some of the newer medications being tested are having dramatic effects and that response rates are improving.

The decision to enter a phase I trial, said Brooks, is "a very personal decision" and often depends on where you are in life. He said younger patients and people with children often want to do everything they can to try to extend their lives, even if only by a few months, while older people may not want to endure additional medical procedures.

Grady said if you're thinking about entering a phase I trial you should have a clear understanding of the drug that's being tested and find out how many people before you have taken the medication. Also, she said, "know what the purpose of the trial is so that your expectations are appropriate."

More information

The U.S. Food and Drug Administration explains more about the risks and benefits of participating in a clinical trial.

SOURCES: Christine Grady, R.N., Ph.D., head of the section on human subjects research, Department of Clinical Bioethics, National Institutes of Health, Bethesda, Md.; Jay Brooks, M.D., chief, hematology and oncology, Ochsner Clinic Foundation Hospital, Baton Rouge, La.; March 3, 2005, New England Journal of Medicine

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