Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: A European organization for research and treatment of cancer randomized study with cross-over

Purpose: To compare the efficacy of paclitaxel versus doxorubicin given as single agents in first-line therapy of advanced breast cancer (primary end point, progression-free survival [PFS]) and to explore the degree of cross- resistance between the two agents, Patients and Methods: Three hundred thirty-one patients were randomized to receive either paclitaxel 200 mg/m(2), 3-hour infusion every 3 weeks, or do xorubicin 75 mg/m(2), intravenous bolus every 3 weeks, Seven courses were p lanned unless progression or unacceptable toxicity occurred before the seve n courses were finished. Patients who progressed within the seven courses u nderwent early cross-over to the alternative drug, while a delayed cross-ov er was optional for the remainder of patients at the time of disease progre ssion. Results: Objective response in first-line therapy was significantly better (P = .003) for daxorubicin (response rate [RR], 41%) than for paclitaxel (R R, 25%), with doxorubicin achieving a longer median PFS (7.5 months for dox orubicin v 3.9 months for paclitaxel, P < ,001), In second-line therapy, cr oss-over to daxorubicin (91 patients) and to paclitaxel (77 patients) gave response rates of 30% and 16%, respectively. The median survival durations of 18.3 months for doxorubicin and 15.6 months for paclitaxel were not sign ificantly different (P = .38), The doxorubicin arm had greater toxicity, bu t this was counterbalanced by better symptom control. Conclusion: At the dosages and schedules used in the present study, doxorub icin achieves better disease and symptom control than paclitaxel in first-l ine treatment, Doxorubicin and paclitaxel are not totally cross-resistant, which supports further investigation of these drugs in combination or in se quence, both in advanced disease and in the adjuvant setting. (C) 2000 by A merican Society of Clinical Oncology.