First-in-human, phase I/IIa dose-escalation and safety study of balugrastim in breast cancer patients receiving myelosuppressive chemotherapy.
OBJECTIVE
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.
Teva Pharmaceuticals, Netanya, Israel.
Noa
N
Avisar
Liat
L
Adar
Jason
J
Bock
Udo
U
Müller
David
D
Shen
Steve
S
Barash
Laurie
L
Pukac
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D011092:Polyethylene Glycols; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012709:Serum Albumin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000075462:Serum Albumin, Human; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012709:Serum Albumin; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000069585:Filgrastim; C000600093:balugrastim; D000075462:Serum Albumin, Human