Gemcitabine in combination with paclitaxel for the treatment of metastatic breast cancer.

Gemcitabine and paclitaxel are active drugs in the treatment of patients with metastatic breast cancer which seem to have synergistic anticancer activity. Seven Phase II trials of gemcitabine/paclitaxel and one Phase III trial have been published. Two dosing or admistration schedules have been preferred in the clinical development of the combinations: gemcitabine on days 1 and 8 plus paclitaxel on day 1 or 8, every 3 weeks or gemcitabine plus paclitaxel on day 1, every 2 weeks. In first-line Phase II trials, up to 71% of patients responded to gemcitabine/paclitaxel therapy. Response rates were lower among patients who had received previous chemotherapy for metastatic disease (46%). Responses were observed in patients refractory to docetaxel monotherapy. Toxicity of gemcitabine/paclitaxel regimens has been low, with infrequent neutropenia or nonhematologic toxicity. In the randomized Phase III registration trial, the gemcitabine/paclitaxel combination demonstrated a clear advantage over paclitaxel alone in terms of the primary end point of survival and other efficacy end points, with manageable toxicity. Gemcitabine/paclitaxel showed a survival advantage of approximately 22% over paclitaxel alone (hazard ratio of 0.775). Gemcitabine plus paclitaxel represents an active and well-tolerated treatment alternative for first-line treatment of anthracycline-treated metastatic breast cancer. Triplet combinations, in which an anthracycline or trastuzumab are added to gemcitabine/paclitaxel, are being explored in the metastatic and neoadjuvant settings with excellent results. In addition, gemcitabine/paclitaxel is being evaluated in two large adjuvant multicenter studies.