Taxoids in combination with epirubicin: the search for improved outcomes in breast cancer

The combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and either doxorubicin or epirubicin has significant activity against metastatic breast cancer. However, the optimal schedule in terms of activity and toxicity is still under investigation. The use of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) in combination with anthracyclines is also active and could represent a safe and favorable alternative. In a phase I trial, 28 patients with metastatic or locally advanced disease received combination chemotherapy using doses of up to 85 mg/m2 docetaxel and 120 mg/m2 epirubicin, with granulocyte colony-stimulating factor support at the higher dose levels. Neutropenia was the dose-limiting toxicity. Severe fluid retention and symptomatic cardiotoxicity were not seen. Responses occurred at doses of 75 mg/m2 docetaxel plus 90 mg/m2 epirubicin and above. However, the proportion of responders did not increase with increasing dose, and the 75 mg/m2 docetaxel/90 mg/m2 epirubicin combination has been selected for further phase II study.