GEMCITABINE PLUS DOCETAXEL FOLLOWED BY CAPECITABINE PROBABLY THE BETTER COMBINATION

Gemcitabine/Docetaxel After Anthracycline Advised for Advanced Breast Cancer

NEW YORK (Reuters Health) Mar 23 - Although the combination of gemcitabine and docetaxel does not provide better survival than capecitabine and docetaxel for patients with metastatic breast cancer, gemcitabine might still be the better option, based on its nonhematologic toxicity profile and the average time to treatment failure.

These findings, from a multicenter European phase 3 trial, were published online March 9 by the Journal of Clinical Oncology.

All 305 women in the study (median age 55 years) had locally advanced or metastatic breast cancer, and all had been treated with an anthracycline. Forty-eight percent had 3 or more disease sites, and 86% had visceral disease.

Participants were randomly selected to receive intravenous (IV) gemcitabine 1,000 mg/m on days 1 and 8, or oral capecitabine 1,250 mg/m twice daily on days 1 through 14. All patients received IV docetaxel, 75 mg/m on day 1 before gemcitabine or capecitabine. Cycles were repeated every 21 days until disease progression or unacceptable toxicity occurred. Median administration in both arms was 6 cycles.

Neither progression-free survival nor overall survival differed significantly between the treatment arms. Median progression-free survival was 8.05 months in the gemcitabine arm versus 7.98 months in the capecitabine arm, and median overall survival was 19.29 months in the gemcitabine arm versus 21.45 months in the capecitabine arm.

Time to treatment failure, however, was significantly longer in the gemcitabine arm (4.24 months) than in the capecitabine arm (4.07 months). The researchers defined time to failure as the interval between the date of randomization and the date of discontinuation, disease progression, death from any cause, or the start of a new anticancer therapy.

Serious hematologic toxicity was not significantly different between the 2 groups, except for grades 3 or 4 leukopenia, which was more common in the gemcitabine group (78% versus 66%). Serious nonhematologic toxicities, however, including diarrhea, hand-foot syndrome and mucositis, were significantly more frequent in the capecitabine group. In addition, fewer patients in the gemcitabine arm (13% versus 27%) discontinued treatment because of drug-related adverse events.

"My personal view," lead author Dr. Stephen Chan, at Nottingham University Hospital, Nottingham, U.K., told Reuters Health, "is that capecitabine as a monotherapy at the lower dose than recommended, i.e., at 2 gram per m daily rather 2.5 gram per m daily, is well tolerated, and in responsive tumors, this can be maintained for a relatively long period of time, sometimes over 12 months.... One strategy for oncologists advising patients is to use the gemcitabine combination as a first line in metastatic breast cancer followed by single agent capecitabine for relapse."