A Southwest Oncology Group randomized phase II study of doxorubicin and paclitaxel as frontline chemotherapy for women with metastatic breast cancer

Purpose. To evaluate whether the high complete response (CR) rates for the combination of doxorubicin and paclitaxel in metastatic breast cancer observed in two European studies could be replicated in a multi-institutional cooperative group trial. Patients and methods. This was a phase II study with 91 patients randomized between either doxorubicin (60 mg/m(2)) followed immediately by paclitaxel (200 mg/m(2) over 3 h) (AT), or with doxorubicin (60 mg/m(2)) followed immediately by cyclophosphamide (600 mg/m(2)) (AC). Treatment was limited to six cycles of therapy for the doxorubicin and paclitaxel combination. Left ventricular ejection fraction was evaluated at on study and after four and six cycles of treatment on AT. Results. Estimates of overall objective response were 31% (with 9% CR) and 39% (with 11% CR) for patients on the AT and AC regimens, respectively. Response was lower than anticipated on the standard AC arm. On average the reduction of LVEF was similar in the two groups, with no patients developing congestive heart failure during the six cycles of therapy, although one patient in the AT group died of delayed congestive heart failure. Conclusions. The results of this multi-institutional study in patients with metastatic breast cancer suggest that the combination of doxorubicin and paclitaxel is well tolerated with relatively low rates of cardiac toxicity if the total dose of doxorubicin is held to less than or equal to360 mg/m(2). However, the CR rates achieved with this combination are probably more modest than initial single institution studies might suggest.