Phase II dose-finding study of balugrastim in breast cancer patients receiving myelosuppressive chemotherapy.

Balugrastim is a once-per-cycle, fixed-dose recombinant protein comprising human serum albumin and granulocyte colony-stimulating factor under development for prevention of severe neutropenia in cancer patients receiving myelosuppressive chemotherapy. This phase II, multicenter, active-controlled, dose-finding pilot study evaluated balugrastim safety and efficacy versus pegfilgrastim in breast cancer patients scheduled to receive myelosuppressive chemotherapy and investigated two doses with similar efficacy to pegfilgrastim for a subsequent phase III study. Patients received four cycles of doxorubicin/docetaxel chemotherapy and with each successive cycle were randomized sequentially to escalating doses of balugrastim [30 (n = 11), 40 (n = 21), or 50 mg (n = 20)] or a fixed dose of pegfilgrastim [6 mg (n = 26)] post-chemotherapy. Balugrastim doses were escalated as planned. The incidence of adverse events was similar among the balugrastim groups and between all balugrastim doses and pegfilgrastim. The most frequently reported adverse events were neutropenia, alopecia, and nausea. During cycle 1, severe neutropenia (absolute neutrophil count of <0.5 × 10(9)/L) occurred in 40, 67, and 50 % and febrile neutropenia occurred in 20.0, 9.5, and 10.0 % of patients receiving balugrastim 30, 40, and 50 mg, respectively; in patients receiving pegfilgrastim, 48 % experienced severe neutropenia and 8 % experienced febrile neutropenia. Duration of severe neutropenia (DSN) for each treatment group was 0.9, 1.6, 1.1, and 0.9 days, respectively. In the remaining three chemotherapy cycles, DSN was ≤1 day across all treatment groups. Balugrastim 50 mg was comparable to pegfilgrastim in terms of safety and overall efficacy in breast cancer patients receiving myelosuppressive chemotherapy.