Abstract
Purpose
To evaluate safety of balugrastim, a recombinant human serum albumin and granulocyte colony-stimulating factor (G-CSF), administered over a range of therapeutic doses in women with breast cancer receiving doxorubicin plus docetaxel chemotherapy.
Methods
The phase I, sequential dose-escalation first segment compared subcutaneous balugrastim 50, 150, 300, and 450 µg/kg during chemotherapy cycles 0–2. The randomized (2:2:1), open-label, phase IIa second segment compared balugrastim 300 or 450 µg/kg with pegfilgrastim 6 mg during chemotherapy cycles 1 and 2.
Results
In the phase I segment, balugrastim was escalated to 450 µg/kg in 13 patients without dose-limiting toxicity. Three (9.7 %) of the 31 adverse events (AEs) reported in nine patients were grade 3 (agranulocytosis, vomiting, hypertension); none was grade 4. In the open-label phase IIa segment (N = 51), the majority of the 64 AEs reported in 31 (75.6 %) balugrastim-treated patients were grade 1 (59.4 %), with 39.1 % grade 2, 1.6 % grade 3 (one AE of vomiting), and none grade 4. Of the 16 AEs reported in seven (70.0 %) pegfilgrastim-treated patients, 87.5 % were grade 1, 6.3 % were grade 2, 6.3 % were grade 3 (one AE of thrombocytopenia), and none were grade 4. Overall, there were six bone pain AEs reported, one in the balugrastim 300 µg/kg group and five in the balugrastim 450 µg/kg group. No AEs in either study necessitated treatment interruption/discontinuation. The incidence and duration of grade 3–4 neutropenia were similar between balugrastim- and pegfilgrastim-treated patients.
Conclusions
Balugrastim was well tolerated in this small population of breast cancer patients.
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Acknowledgments
Medical writing and editorial assistance was provided by Ruth Sussman, Chameleon Communications, New York, NY, and Lisa Feder, PhD, Peloton Advantage, Parsippany, NJ, and was funded by Teva Branded Pharmaceutical Products R&D, Inc. The authors also acknowledge Scott Newcomer, MS, Teva Pharmaceuticals, Frazer, PA, and Pippa Loupe, PhD, Teva Pharmaceuticals, Kansas City, MO, for their medical writing and editorial assistance in the development of this manuscript. Teva provided a full review of the article. This study was sponsored by Teva Biopharmaceuticals USA (formerly CoGenesys, Inc).
Conflict of interest
Noa Avisar and Liat Adar are employees of Teva Pharmaceuticals, Netanya, Israel. Laurie Pukac, Jason Bock, and Steve Barash are employees of Teva Biopharmaceuticals, Rockville, MD, and Udo Müller is an employee of Teva GmbH, Ulm, Germany, both subsidiaries of Teva Pharmaceuticals. David Shen was an employee of Teva Pharmaceuticals at the time of this study and during manuscript preparation.
Ethical standard
This study was approved by the appropriate ethics committee at each study site and was conducted in accordance with the International Conference on Harmonisation guidelines for Good Clinical Practice and the current version of the Declaration of Helsinki (Tokyo, 2004). All study participants provided written informed consent prior to their participation.
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EudraCT Number: 2006-005997-28
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Avisar, N., Adar, L., Bock, J. et al. First-in-human, phase I/IIa dose-escalation and safety study of balugrastim in breast cancer patients receiving myelosuppressive chemotherapy. Cancer Chemother Pharmacol 75, 929–939 (2015). https://doi.org/10.1007/s00280-015-2703-1
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DOI: https://doi.org/10.1007/s00280-015-2703-1