Prospective multicenter randomized phase III study of weekly versus standard XXXX (D2) for first-line treatment of metastatic breast cancer.

@entity1 @entity137 @entity417 @entity882 @entity1431 @entity1205 @entity2359
PURPOSE: Previous phase II studies have indicated a greatly reduced hematotoxicity of @entity1205 -based regimens administered on weekly schedules. The present trial was initiated to randomly compare the @entity137 and efficacy of weekly @entity1205 versus its standard 3-weekly application. METHODS: @entity1 previously untreated with chemotherapy for metastatic disease were recruited. @entity1 aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. @entity1 were randomized to receive @entity1205 either on a 3-weekly [75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable @entity137 , or disease progression. All @entity1 received standard corticosteroid prophylaxis. RESULTS: Since statistical significance for the primary endpoint ( @entity137 ) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 @entity1 ). Compared to the standard arm, @entity1431 >= grade 3 was a rare event in the weekly arm of the D2 study (per- @entity1 analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of @entity417 or @entity882 . With regard to nonhematological @entity137 , there was a higher incidence of skin/nail and hepatological @entity137 with the weekly schedule, whereas @entity2359 was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24). CONCLUSION: The present data support the feasibility of both weekly and 3-weekly application of @entity1205 . As expected, severe @entity1431 seems avoidable in weekly scheduled single-agent @entity1205 and may serve as an important treatment option, particularly in elderly @entity1 and @entity1 with a reduced performance status.
