Paclitaxel and epirubicin as first-line therapy for patients with metastatic breast cancer.

Paclitaxel (Taxol), has aroused considerable interest for its high single-agent activity in breast cancer and novel mechanism of action. Epirubicin (Farmorubicin), the 4'epimer of doxorubicin (Adriamycin), also has high activity in breast cancer, with the advantage of a lower rate of toxic side effects-especially cardiac effects-compared with its parent compound. The combination of paclitaxel and doxorubicin has yielded response rates between 63% and 94% in phase I/II studies, but authors reported severe cardiac toxic events. The goal for the current study was to evaluate the combination of paclitaxel and epirubicin, focusing mainly on cardiac toxicity. Of a total of 85 patients entered, 68 patients with metastatic breast cancer were evaluable. Nearly 20% had primary metastatic breast cancer with large tumors. Half had received adjuvant chemotherapy. Study medication in Group A consisted of 60 mg/m2 epirubicin given over 1 hour, followed by paclitaxel 175 mg/m2 as a 3-hour IV infusion. In Group B, 90 mg/m2 epirubicin was combined with 175 mg/m2 paclitaxel, delivered as for Group A. The main toxicity in both groups was neutropenia. In Group A, the paclitaxel dose could be escalated to 200 mg/m2 in 15 patients and to 225 mg/m2 in 7 patients; dose reduction due to severe neutropenia was necessary in 11 patients. No cardiac adverse events were reported in Group A. In Group B, only one patient could be escalated to 200 mg/m2 but three patients required a dose reduction. In this group, one patient had a decrease of left ventricular ejection fraction of more than 10% without any clinical signs. Of 43 patients in Group A and 25 in Group B, the response rate was 67% in Group A and 68% in Group B. The duration of response was 8.2 months in both groups. The combination of paclitaxel 175 mg/m2 and epirubicin 60 mg/m2 or 90 mg/m2 can be safely administered. The response data were encouraging and further evaluation is warranted.