Coordinated by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), the ExCel research study will examine the potential benefit of exemestane and its ability to prevent breast cancer in women who are at increased risk for the disease. Exemestane - part of a class of drugs called aromatase inhibitors - suppresses estrogen production, a key component in the development of some types of breast cancer. Exemestane could provide women with an alternative option to tamoxifen, the only drug FDA approved for prevention of breast cancer.
"Breast cancer is a major public health issue - every 30 seconds somewhere in the world a woman is diagnosed with this disease," says Dr. Paul Goss, the ExCel research study chair.
"Thousands of women have already beat breast cancer thanks to recent research on aromatase inhibitors. As a result, we think this could be an effective approach to preventing it from developing in the first place."
The ExCel research study will follow more than 4,500 postmenopausal women from the U.S., Canada and Spain over a five year period. To be eligible, women must be 35 years of age or older and have an increased risk of developing breast cancer. Risk factors can include a woman's age, her family history of breast cancer, her age at first menstrual period and her age at first live birth.
Initial results of the trial could be available within four years and study investigators hope to see as much as a two-thirds reduction in the incidence of breast cancer among women in the treatment group.
Aromatase inhibitors are currently being used to treat breast cancer in women around the world and results from a study published in a March 2004 issue of the New England Journal of Medicine demonstrated that exemestane can prevent the occurrence of new cancers in the opposite breast of women who have already had breast cancer, suggesting that it may also be able to prevent the disease in healthy women.
Clinical studies have also shown that aromatase inhibitors are associated with fewer serious side effects than tamoxifen, the only other drug available to women for primary breast cancer prevention.
"While tamoxifen has already been shown to reduce the incidence of primary breast cancer, many women choose not to take this drug because of its known side effects," says Dr. Goss, also Director of Breast Cancer Research at the Massachusetts General Hospital and Professor of Medicine at Harvard Medical School. "Results of this study will provide women with important information about another potentially effective tool for breast cancer prevention."
Women enrolled in the ExCel research study will be randomized to one of two groups and all will take one pill per day for five years. Group A will take exemestane and Group B will take a placebo. Women will participate in two follow-up visits during the first year - at six and 12 months - and then an annual follow-up visit during years two through five.
Women will have a screening visit with a member of the study's clinical staff to see if they are eligible for the trial. If eligible, they will undergo a routine health examination, routine blood tests, a mammogram and a bone mineral density test.
The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), based at Queen's University in Kingston Ontario, is working in cooperation with physicians in Canada, the U.S. and Spain to coordinate the ExCel research study.
Founded in 1971 and funded by the Canadian Cancer Society, the NCIC CTG develops, conducts and analyzes national and international trials of cancer therapy, including trials for new cancer drugs, cancer prevention and supportive care to improve quality of life for people with cancer. Since its inception, the NCIC CTG has enrolled more than 40,000 patients from Canada and around the world in over 300 clinical trials.
Pfizer, Inc. manufactures exemestane under the brand name Aromasin® and is providing the drug for the trial.
Women looking for more information about the ExCel research study and participating study centers in their community can visit www.excelstudy.com or call toll-free:
Exemestane (Aromasin) was approved in the United States late in 1999 for the treatment of advanced breast cancer in postmenopausal women whose tumors have stopped responding to tamoxifen. Exemestane is approved by the FDA and Health Canada and is marketed by Pfizer, Inc. as Aromasin®. It is also approved for use in Europe, Japan, and South America. It is currently used for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
Results of the Intergroup Exemestane Study, published in the New England Journal of Medicine, revealed that 32 percent fewer women had a recurrence in their breast cancer when they switched to exemestane after two to three years of tamoxifen compared to those who continued on tamoxifen for a total of five years, the current standard of care. Additionally, twice as many women receiving tamoxifen developed second (or new) breast cancers than those treated with exemestane.
Unlike other aromatase inhibitors, exemestane is a steroidal aromatase inactivator, which means it selectively targets and irreversibly binds to the aromatase enzyme, which is required to produce estrogen. Without estrogen, breast cancer cells cannot survive. Exemestane is well tolerated and the side effects associated with the treatment are generally predictable and manageable. Given its potent suppression of estrogen, exemestane has been associated with low instances of mild nausea and hot flashes.