Cancellation of a Clinical Trial: Has An Injustice Been Done to Women?

The Wall Street Journal on Tuesday examined the reasoning behind the National Cancer Institute's decision in June to cancel a five-year, $100 million study designed to test the new class of breast cancer prevention drugs known as aromatase inhibitors. The trials were to be conducted by the Pittsburgh, Pa.-based National Surgical Adjuvant Breast and Bowel Project, which has enrolled more than 110,000 women and men in trials of breast and colorectal cancer treatments (Parker-Pope, Wall Street Journal, 8/14).
Tamoxifen, which blocks the production of estrogen, is the only FDA-approved drug for reducing breast cancer risk, but it increases risk for uterine cancer and blood clots. Another estrogen-blocking drug, called raloxifene, has been shown to be equally effective as tamoxifen at reducing breast cancer risk, but it increases risk of hot flashes and other menopause-related symptoms.

Aromatase inhibitors work by blocking the production of estrogen. The study would have involved administering either raloxifene or the aromatase inhibitor letrozole to 12,800 women at high risk of developing breast cancer at 500 sites in the U.S. and Canada. A committee appointed by NCI Director John Niederhuber in June decided not to endorse the study, citing the cost and questions concerning its usefulness and safety. In addition, the committee said that two large U.S. and England-based studies of the drugs are under way (Kaiser Daily Women's Health Policy Report, 6/20).

Reaction, Outlook
Study researchers have appealed the cancellation to NIH Director Elias Zerhouni, the Journal reports. NSABP in a letter to Zerhouni appealing the cancellation said it "represents a dangerous and unjustified departure" from NCI's traditional review process. NSABP Chair Norman Wolmark said the group is "passionate in [its] belief this is an extremely useful trial that will benefit women," adding that the group "think[s] an injustice has been done to women by canceling the trial."

Niederhuber has said that the agency's funds would be better spent on identifying characteristics that indicate increased breast cancer risk instead of giving preventive drugs to women who might not have a high risk of developing the disease. According to the Journal, NCI also is concerned about possible side effects of the drugs.

Niederhuber in a letter to Sen. Arlen Specter (R-Pa.), who had inquired about the study's cancellation, said there was evidence that healthy women did not want to take drugs to prevent breast cancer because of potential side effects. Niederhuber added that although previous trials of breast cancer prevention drugs have provided "valuable information," they "failed to change the practice of breast cancer prevention among women and their health care providers." Carolina Hinestrosa -- executive vice president of the National Breast Cancer Coalition, which supports the cancellation -- said the group is "very concerned about the approach of treating healthy women with drugs that are toxic in order to reduce the risk for very few who benefit."

According to the Journal, letrozole likely will not be approved for breast cancer prevention if the trial does not take place because such a trial likely would be too expensive for the private sector. Some researchers said that other proposals for clinical trials of breast cancer prevention drugs are unlikely if NIH upholds NCI's decision. The journal Lancet in a recent editorial said the cancellation was "troubling" and that an "independent investigation into how the decision was made and whether it was made fairly is warranted." NCI declined to comment on the editorial but said Niederhuber "got the best scientific advice and acted on it" in canceling the study (Wall Street Journal, 8/14).

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