This study evaluated the safety and feasibility of the combination of paclitaxel (Taxol) and epirubicin, the 4'-epimer of doxorubicin, in women with metastatic breast cancer. A total of 85 patients with histologically proven metastatic breast cancer were treated in two cohorts; epirubicin 60 mg/m2 i.v. infused over 1 hour, followed by paclitaxel 175 mg/m2 i.v. infused over 3 hours (group A), and epirubicin 90 mg/m2 i.v. via a 1-hour infusion, followed by paclitaxel 175 mg/m2 i.v. via a 3-hour infusion (group B). Of the 85 patients, 68 were evaluable for response and toxicity (43 in group A and 25 in group B). The combination was generally well tolerated. The higher epirubicin dose induced more severe neutropenia and one case of cardiotoxicity. Nonhematologic toxicities were mild, with no severe mucositis or peripheral neuropathy reported. Overall, 68% of patients in group A and 68% of patients in group B responded. A phase III trial comparing paclitaxel, 175 mg/m2, plus epirubicin, 60 mg/m2, with the standard combination of epirubicin, 60 mg/m2, and cyclophosphamide (Cytoxan, Neosar), 600 mg/m2, is currently in progress.