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

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Abstract

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 × 109/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.

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Acknowledgments

This study was sponsored by Teva Branded Pharmaceutical Products R & D, Inc. Medical writing assistance was provided by Lisa Feder, PhD of Peloton Advantage, LLC, and was funded by Teva Branded Pharmaceutical Products R & D, Inc. Teva provided a full review of the article.

Conflict of interest

Steven Barash, Liat Adar, Peter Bias, and Noa Avisar are employees of Teva Pharmaceuticals. Oleg Gladkov, Vladimir Moiseyenko, and Igor N. Bondarenko declare that they have no conflict of interest. Yaroslav Shparyk has received consulting fees/honoraria as a principal investigator from Teva Pharmaceuticals.

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Authors and Affiliations

  1. Chelyabinsk Regional Clinical Oncology Dispensary, Chelyabinsk, Russia

    Oleg Gladkov

  2. N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia

    Vladimir Moiseyenko

  3. Dnepropetrovsk Medical Academy, City Clinical Hospital #4, Dnepropetrovsk, Ukraine

    Igor N. Bondarenko

  4. Lviv Cancer Center, Lviv, Ukraine

    Yaroslav Shparyk

  5. Teva Biopharmaceuticals, Rockville, MD, USA

    Steven Barash

  6. Teva Pharmaceuticals, Inc., Netanya, Israel

    Liat Adar & Noa Avisar

  7. Teva Ratiopharm, Ulm, Germany

    Peter Bias

Authors
  1. Oleg Gladkov
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  2. Vladimir Moiseyenko
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  3. Igor N. Bondarenko
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  4. Yaroslav Shparyk
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  5. Steven Barash
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  6. Liat Adar
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  7. Peter Bias
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  8. Noa Avisar
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Corresponding author

Correspondence to Noa Avisar.

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Gladkov, O., Moiseyenko, V., Bondarenko, I.N. et al. Phase II dose-finding study of balugrastim in breast cancer patients receiving myelosuppressive chemotherapy. Med Oncol 32, 181 (2015). https://doi.org/10.1007/s12032-015-0623-x

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  • DOI: https://doi.org/10.1007/s12032-015-0623-x

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