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

Chemistry

Medicinal Chemistry

Author(s): Colomer R

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Abstract 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. This article was published in Womens Health (Lond) and referenced in Medicinal Chemistry

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