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Doxorubicin and Paclitaxel Versus Doxorubicin and Cyclophosphamide as First-Line Chemotherapy in Metastatic Breast Cancer: The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial

From the Investigational Drug Branch for Breast Cancer, European Organization for the Research and Treatment of Cancer Data Center, and Jules Bordet Institute, Brussels, Belgium; Institute of Oncology, Ljubljana, Slovenia; Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, the Netherlands; Weston Park Hospital National Health Service Trust, Sheffield; Newcastle General Hospital, Newcastle-Upon-Tyne; and University of Glasgow, Glasgow, United Kingdom; Regina Elena Institute, Rome, Italy; Centre Georges-François Leclerc, Dijon, France; and Rambam Medical Centre, Haifa, Israel.

Address reprint requests to Martine Piccart, Jules Bordet Institute, Bd de Waterloo 125, 000 Brussels, Belgium; email: martine.piccart{at}bordet.be

PURPOSE: To compare the efficacy and tolerability of the combination of doxorubicin and paclitaxel (AT) with a standard doxorubicin and cyclophosphamide (AC) regimen as first-line chemotherapy for metastatic breast cancer.

PATIENTS AND METHODS: Eligible patients were anthracycline-naive and had bidimensionally measurable metastatic breast cancer. Two hundred seventy-five patients were randomly assigned to be treated with AT (doxorubicin 60 mg/m² as an intravenous bolus plus paclitaxel 175 mg/m² as a 3-hour infusion) or AC (doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m²) every 3 weeks for a maximum of six cycles. A paclitaxel (200 mg/m²) and cyclophosphamide (750 mg/m²) dose escalation was planned at cycle 2 if no grade 3 neutropenia occurred in cycle 1. The primary efficacy end point was progression-free survival (PFS). Secondary end points were response rate (RR), safety, overall survival (OS), and quality of life.

RESULTS: A median number of six cycles were delivered in the two treatment arms. The relative dose-intensity and delivered cumulative dose of doxorubicin were lower in the AT arm. Dose escalation was only possible in 17% and 20% of the AT and AC patients, respectively. Median PFS was 6 months in the two treatments arms. RR was 58% versus 54%, and median OS was 20.6 versus 20.5 months in the AT and AC arms, respectively. The AT regimen was characterized by a higher incidence of febrile neutropenia, 32% versus 9% in the AC arm.

CONCLUSION: No differences in the efficacy study end points were observed between the two treatment arms. Treatment-related toxicity compromised doxorubicin-delivered dose-intensity in the paclitaxel-based regimen

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