Pilot Trial of Alternating Paclitaxel and Doxorubicin in Advanced Breast Cancer

Abstract: Studies combining paclitaxel and doxorubicin in the treatment of metastatic breast cancer have shown dose-limiting toxicities and raised questions relating to the risk of cardiac toxicities. This pilot trial evaluates an alternating approach to assess safety and feasibility of paclitaxel alternating with doxorubicin as chemotherapy for recurrent breast cancer. Twelve patients with measurable or evaluable breast cancer who had received no more than one prior chemotherapy (either as adjuvant therapy or therapy for metastatic disease) and no prior anthracycline- or taxane-containing chemotherapy were included. Paclitaxel was administered at 200 mg/² as a continuous 24-hour intravenous infusion alternating with doxorubicin at 75 mg/m² intravenously, administered every 21 days for a maximum of 10 cycles of therapy. Objective responses were observed in seven of 12 patients (58%) (three complete responses and four partial responses). Objective responses were seen in lymph node, visceral, soft tissue, and bony sites of metastases. The median duration of response was 9.6 months (range 1.4–20.6). A total number of 102 cycles of therapy were administered with 8 of 12 patients tolerating all 10 cycles (median of 10 cycles per patient, range 2–10). Adverse effects included mild myalgias, arthralgias, and peripheral neuropathies. Cardiac toxicities included asymptomatic sinus tachycardia, sinus bradycardia, and nonspecific T-wave abnormality. One patient experienced left ventricular failure. There were no serious hypersensitivity reactions. Paclitaxel cycles resulted in lower granulocyte nadirs than doxorubicin cycles. There were no significant differences in thrombocytopenia between the two agents. The feasibility of administering paclitaxel and doxorubicin in alternating cycles was demonstrated. This was a well-tolerated regimen with results supportive of safety in administration in an alternating regimen.