Gemcitabine plus taxane combinations in metastatic breast cancer:a comprehensive review

Gemcitabine and the taxanes (paclitaxel and docetaxel) exhibit a synergistic anticancer activity and are active in the treatment of metastatic breast cancer. Many trials have investigated the efficacy and toxicity of gemcitabine plus paclitaxel, including one Phase III trial. Gemcitabine has also been studied in combination with docetaxel and again, in a Phase III trial. In first-line Phase II trials, 61% of patients responded to gemcitabine plus paclitaxel therapy and 64% have responded to gemcitabine plus docetaxel. Response rates were lower among patients who had received previous chemotherapy for metastatic disease (46% and 52%, respectively). Toxicity of the gemcitabine plus paclitaxel regimens was generally low, with few cases of neutropenia or non-haematological toxicity. Gemcitabine plus docetaxel was seen to be slightly more toxic in terms of neutropenia and fatigue. Results of a randomised Phase III registration trial of gemcitabine plus paclitaxel versus single-agent paclitaxel show a clear advantage for the combination in terms of survival, with little added toxicity. Gemcitabine plus paclitaxel improved overall survival by approximately 25% compared with paclitaxel alone. A Phase III trial comparing gemcitabine plus docetaxel with capecitabine plus docetaxel showed similar efficacy results, with more toxicity in the capecitabine arm. The efficacy of triplet combinations of gemcitabine plus paclitaxel plus an anthracycline or trastuzumab are being explored in the metastatic and neoadjuvant setting with excellent response results. Two very large trials in Europe and the US are evaluating the incorporation of gemcitabine into sequential adjuvant therapy in post-operative breast cancer.