Leading cancer doctor calls for new guidelines to control early reporting from clinical trials

03/16/04

Hamburg, Germany: A leading breast cancer doctor is urging researchers to consider changing the guidelines that govern whether clinical trials should be stopped prematurely, as she believes that current practice could be damaging research efforts.

Dr Martine Piccart, head of the chemotherapy unit at the Institut Jules Bordet, Brussels, Belgium, is putting proposals for new guidelines to the Breast International Group (BIG) and, if BIG agrees, the issue would be discussed with the North American Breast Intergroup.

She said that breast cancer research had not been well served by trials of adjuvant therapies aimed at preventing cancer returning, which had reported their results early, because this could mean that some questions about long-term efficacy and side effects or untoward effects remained unanswered, and the future of other trials was put at risk.

"Researchers need to achieve a better balance between informing doctors and women quickly about a more effective treatment for breast cancer and the equally important need to collect solid data on the safety of the therapy," she told a discussion group at the 4th European Breast Cancer.

Three recent trials* of aromatase inhibitors (AIs) as adjuvant treatments for breast cancer had all reported results early because they showed significant advantages for AIs over tamoxifen, but Dr Piccart said that an average follow-up time of only 30 months did not enable doctors to weigh up the long-term risks and benefits of the different treatments. If the trials had continued for longer it was possible that the risks of the different treatments would have become clearer (for instance, tamoxifen carries a risk of endometrial cancer and blood clots, whereas AIs carry a risk of osteoporosis and bone fractures), therefore allowing doctors to conduct a useful risk-benefit analysis an integral part of making appropriate decisions about the best treatment for a patient.

She said early reporting from one of the trials (MA17 trial on the AI, letrozole) had, in effect, "killed" a sister trial looking at another AI, exemestane, instead of letrozole for extended adjuvant therapy, and other studies were in danger too.

"I suggest that guidelines should be drawn up and agreed by the research community, whereby early disclosure is based on significant differences between the rates of distant relapse. Distant relapses mean the cancer recurring in lung, liver or bone, for which there is almost no chance of cure, in contrast to relapses in the breast and regional nodes for which curative therapy exists. I will be putting this proposal to the Breast International Group and, if deemed appropriate, it will be discussed with its closest partner, the North American Breast Intergroup."

Her remarks come hot on the heels of the announcement last week that exemestane, a steroidal aromatase inhibitor (SAI), was more effective than tamoxifen in preventing cancer returning in women whose breast cancer had been caught early. This trial, led by Professor Charles Coombes of Imperial College London, reported early, although 90 per cent of participants had completed their therapy by this time.

Dr Piccart warned that big questions still remain about the long-term effects and effectiveness of AIs, and she urged physicians to make "individualized" treatment decisions with their patients.

"Although there have been several trials now that show positive results for AIs, the long-term effects are still unclear. Questions remain about their effect on bone and cardiovascular health, cognitive and sexual function, and quality of life," she said. "The biggest question is which will be the optimal new endocrine therapy: an AI upfront instead of tamoxifen or a few years of tamoxifen followed by an AI? Also, should the AI be given for two or three years, or for five years, as is now current practice with tamoxifen? At present no-one can say what is the best treatment strategy for AIs."

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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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Don't be too timid and squeamish about your actions. All life is an experiment. The more experiments you make the better.
-- Ralph Waldo Emerson