The results of a major international trial of the cancer drug letrozole were so promising that investigators decided to stop the trial early.
Breast cancer patients taking letrozole, one of a new class of drugs called aromatase inhibitors, had about half the rate of cancer recurrences as women taking a placebo.
"The results are absolute, confirmed and credible," says study investigator Dr. Paul Goss. “An independent monitoring committee recommended that we stop the study by preset statistical boundaries, which we exceeded by at least tenfold."
TAMOXIFEN BENEFITS AND RISKS
An older drug called tamoxifen has helped women who have estrogen-receptor-positive breast cancer; that is, cancer fueled by the hormone estrogen.
Tamoxifen reduces the risk of recurrence by 47% and the risk of death by 26% for five years after surgery.
Unfortunately, when tamoxifen is used for longer than five years, it may actually promote the growth of cancer cells.
Women who are more than five years past surgery represent the largest subgroup of women with breast cancer, Goss says.
"'What is unrecognized is that over 50% of recurrences unfortunately occur beyond five years after diagnosis," Goss says. "Because it continues to relapse almost indefinitely, there is no limit to the disease."
Doctors have lacked any appropriate tools for the hundreds of thousands of women who enter that critical post-five-year period every year. Until now.
THE STUDY
The letrozole trial started enrolling participants in 1998 and ended up with 5,187 women in Canada, the United States and Europe who were postmenopausal, had hormone-receptor-positive tumors and had been taking tamoxifen for approximately five years. All of the women had to be within three months of stopping tamoxifen and all were disease-free when enrolled. The trial was coordinated by the National Cancer Institute of Canada.
The participants in Goss's study received either 2.5 milligrams (mg) of letrozole or a matching placebo daily for five years. Letrozole reduced the risk of recurrence by 43%.
SIDE EFFECTS
The median follow-up was only 2.4 years when the trial was stopped. There are some drawbacks to stopping a trial early, including questions about side effects and the effectiveness of the drug over time.
At the time of the study's eady closure, the number of women who were experiencing side effects in the placebo and the letrozole groups was approximately the same, except in the rate of bone thinning, which was slightly higher in the letrozole group.
Tamoxifen provides protection against bone fractures, but it contributes to endometrial cancer and blood clots. Women considering letrozole therapy need to discuss with their doctor ways to mitigate the risk of osteoporosis.
Letrozole has been approved by the US Food and Drug Administration (FDA) for the treatment of some forms of breast cancer.
The American Cancer Society has more information on cancer drugs at www.cancer.org.
