Clinical Trials Results Indicate New Ways to Use Drugs
To Treat Breast Cancer
The results from several clinical trials, presented at the American Society of Clinical Oncology (ASCO) annual meeting in New Orleans last week highlight research progress that spans the continuum of breast cancer - from prevention to reducing the risk of recurrence to treating advanced disease. The trials included exploring new hormonal therapies that may reduce cancer risk, developing alternatives to tamoxifen in the adjuvant setting, and optimizing chemotherapy dosing schedules.
One of the most significant findings pertains to decreasing the dosing interval for the chemotherapeutic agent, paclitaxel (Taxol), for women with metastatic breast cancer. The trial, conducted by the Cancer and Leukemia Group B (CALGB), a Cooperative Group funded by the National Cancer Institute (NCI), examined the effects of weekly administration of paclitaxel versus the standard 3-week schedule on tumor response and delay of disease progression.
Forty percent of patients who received paclitaxel weekly responded to treatment compared with 28 percent of patients on the standard regimen. Disease progression was 9 months with weekly chemotherapy versus 5 months with standard chemotherapy.
"The weekly schedule is well tolerated and appears more effective in the metastatic setting. This result parallels a previous CALGB study reported last year that also reduced the dosing interval for paclitaxel in combination with other drugs and showed a beneficial effect," said Dr. Jeffrey Abrams, acting chief of the Clinical Investigations Branch at NCI's Cancer Therapy Evaluation Program.
Other results presented at the meeting included updated findings from an international clinical trial of the drug letrozole (Femara) in reducing the risk of recurrent breast cancer after 5 years of tamoxifen therapy. Initial results of the trial, led by the National Cancer Institute of Canada, demonstrated that letrozole significantly reduced the risk of recurrence when taken after 5 years of tamoxifen therapy.
New data, with a median follow-up of 2.5 years, demonstrated that letrozole reduced metastasis by 40 percent compared with placebo in both node-negative and node-positive patients. There was also a 39-percent increase in overall survival for node-positive patients taking letrozole. "Of equal interest to the good news on survival," said Dr. Abrams, "was that additional follow-up did not show any further increase in side effects related to bone fractures or the heart.
"Encouraging results were also seen in prevention. The Continuing Outcomes Relevant to Evista (CORE) study allowed women with osteoporosis, who had been initially randomized to raloxifene (Evista) or placebo for 4 years, to undergo a second randomization to raloxifene or placebo for an additional 4 years. Women taking raloxifene had a 59 percent lower risk of breast cancer after 4 years on the follow-up trial compared with those taking the placebo. Similar to results reported from the Tamoxifen Prevention Trial, the incidence of ER-positive breast cancer was reduced by 66 percent but there was no reduction in ER-negative cancers.
Researchers cautioned that these results may be limited because the study included only postmenopausal women with osteoporosis; it is not clear if the results will hold true for other women.
It is premature to recommend that postmenopausal women take raloxifene outside of a clinical trial to reduce their risk of breast cancer, according to Dr. Silvana Martino, the principal investigator of the CORE study. She noted that two large trials with raloxifene are underway, including the STAR trial, which is comparing raloxifene with tamoxifen in the prevention of breast cancer.