TUESDAY, Nov. 2, 2004 (HealthDayNews) -- There has been a dramatic decrease in the number of deaths caused by experimental cancer drugs used in early phase clinical trials in the United States, a new study finds.
Such trials are the first step in the process to gain federal government approval for a new drug. Their purpose is to determine if the drug is safe; whether the medicine is effective is usually not a matter of concern in early phase trials.
"We were interested in trying to understand trends in the safety of clinical trials," explained lead researcher Dr. Thomas G. Roberts Jr., of Massachusetts General Hospital and Harvard Medical School.
Roberts' team found the odds of a patient experiencing toxic death from an experimental cancer drug in an early, phase 1 trial deceased by 91 percent from 1991 to 2002. That sharp drop can be attributed to safer experimental drugs, more use of medications that counteract the toxic effects of experimental drugs, and better oversight from both the government and medical institutions, the researchers noted.
The team looked at trials of experimental cancer drugs; there are more than 550 phase 1 trials open to cancer patients at any given time in the United States. "These trials are considered among the riskiest in all of medicine," Roberts said.
The results of 213 published studies of phase 1 trials included a total of 6,474 patients. Deaths from a toxic reaction to the drugs studied went from 3.8 percent in trials conducted from 1991 to 1994 to 0.06 percent in trials conducted from 1999 to 2002, according to the report.
The study appears in the Nov. 3 issue of the Journal of the American Medical Association.
There are several explanations for the increased safety of such trials, Roberts said. First, the types of drugs being tested have changed. Toxic chemotherapy drugs have given way to more targeted, safer drugs.
"Patients who received targeted therapy had four times less odds of experiencing a toxic death than patients who received a traditional chemotherapy drug," Roberts said.
Second, the use of other supportive drugs to offset toxic effects has reduced the number of deaths. Third, the oversight of trials both from the federal government and the institutions conducting the trials has improved, Roberts said.
"However, we cannot exclude the possibility that there is bias in our results," Roberts added. Sometimes trials that have negative results go unpublished, he noted.
"We owe it to patients to make trials as safe as possible," Roberts said. "If patients believe that trials are unsafe, then we will have more difficulty in recruiting patients to participate in these trials."
Roberts speculated that as researchers have become more concerned about patient safety they have lowered the doses of the experimental drugs, which may reduce their therapeutic value. In its study, Roberts' group saw a steady decline in the response rate to the drugs being tested as safety increased.
Despite this, Roberts said, "We are having incremental improvement in the treatment of cancer in general. And we are having true breakthroughs in certain subsets of certain cancers."
In addition, as treatments become more targeted, trials are becoming more selective in the patients who are accepted. Volunteers are more likely to undergo genetic testing before being accepted into a trial to ensure a higher response rate to the drug being tested, Roberts said.
"I don't know how much safer we can get," Roberts said. "But we have to focus on making these trials more efficient and also increasing the chance for benefit."
Dr. Eric X. Chen, of Toronto's Princess Margaret Hospital and the University of Toronto, said, "We need to look into other study designs that improve the risk-benefit ratio in phase 1 trials."
Chen and his colleague, Dr. Ian F. Tannock, noted in an accompanying editorial in the journal that people who participate in clinical trials, as well as their doctors, have an expectation that the drug being tested will benefit them.
"We should look at study designs to improve the benefit," Chen said. He believes that as treatments become more targeted to specific types of cancers, patient selection will improve, increasing both safety and efficacy.
"Patients thinking of participating in a clinical trial should talk with their doctor, read the consent form carefully and realize that despite our efforts, the potential benefit is low," Chen said.
More information
The National Institutes of Health can tell you more about clinical trials.
