Multicenter Randomized Trial Comparing Sequential With Concomitant Administration of Doxorubicin and Docetaxel As First-Line Treatment of Metastatic Breast Cancer: A Spanish Breast Cancer Research Group (GEICAM-9903) Phase III Study

Abstract

PurposeThis randomized, multicenter, phase III trial evaluated whether sequential doxorubicin and docetaxel (A→T) reduced hematological toxicity, especially febrile neutropenia, compared with concomitant (AT) administration as first-line chemotherapy in metastatic breast cancer (MBC).Patients and MethodsOne hundred forty-four patients were randomly assigned to receive three cycles of doxorubicin 75 mg/m2every 21 days followed by three cycles of docetaxel 100 mg/m2, every 21 days (A→T) or six cycles of the combination doxorubicin 50 mg/m2and docetaxel 75 mg/m2(AT) every 21 days. Patients previously treated with anthracyclines received two cycles of doxorubicin followed by four cycles of docetaxel (A→T), or three cycles of AT followed by three cycles of docetaxel 100 mg/m2every 21 days.ResultsFebrile neutropenia was less common in the A→T arm (29.3% of patients, 6.9% of cycles) compared with the AT arm (47.8% of patients, 14.8% of cycles; P = .02 and P = .0004, respectively). Asthenia, diarrhea, and fever occurred more frequently in the AT arm. The overall responses rates were 61% in the A→T arm (95% CI, 50% to 72%) and 51% in the AT arm (95% CI, 39% to 63%). The median duration of response was 8.7 months (A→T) and 7.6 months (AT); the median time to progression was 10.5 months (A→T) and 9.2 months (AT); the median overall survival was 22.3 months (A→T) and 21.8 months (AT); and no significant differences were found.ConclusionA→T significantly reduced febrile neutropenia compared with AT in MBC patients and maintains comparable antitumoral efficacy. A→T represents a valid option for the treatment of MBC.