Phase 1 study of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in breast cancer patients after autologous peripheral blood progenitor cell (PBPC) transplantation.
Forty-seven patients with stage II, III, or IV breast cancer undergoing autologous peripheral blood progenitor cell (PBPC) transplantation were randomized to placebo (n = 13) or to one of five sequential dose cohorts of pegylated (PEG) recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) (1.0, 2.5, 5.0, 7.5, or 10.0 microg/kg/day) (n= 34). Blinded study drug was started on the day of transplantation and was continued until the platelet count was > or =100 x 109/l or a maximum of 21 days. PBPCs were mobilized with filgrastim (r-metHuG-CSF) and all patients received filgrastim starting on day +2 after transplantation. The nadir platelet count was not affected by treatment. The median time to platelet recovery was 11 and 12 days for the placebo and combined PEG-rHuMGDF groups, respectively. No trends in adverse events suggested dose- or treatment-related toxicity. Two patients withdrew from the study because of an adverse event (allergic reaction in the 7.5 microg/kg group) probably related to study drug, and veno-occlusive disease (VOD) (in the 5 microg/kg group) which was felt not to be related to study drug by the investigator. No patients developed neutralizing antibodies to MGDF. Day +21 and day +28 platelet counts were higher in the group receiving PEG-rHuMGDF (246 vs 148 x 109/l and 299 vs 145 x 109/l, respectively; both P < 0. 05). PEG-rHuMGDF up to 10 microg/kg/day was well tolerated. In this study, there was no effect of study drug on initial platelet engraftment at the doses studied. However, the efficacy of other doses is unknown.
The Cleveland Clinic Foundation, OH 44195, USA.
B
B
Bolwell
J
J
Vredenburgh
B
B
Overmoyer
C
C
Gilbert
L
L
Chap
D M
DM
Menchaca
S
S
Cruickshank
J
J
Glaspy
D000328:Adult; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D015331:Cohort Studies; D003257:Consumer Product Safety; D004341:Drug Evaluation; D005260:Female; D000069585:Filgrastim; D006085:Graft Survival / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000633:toxicity; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000592:standards; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D013921:Thrombocytopenia / Q000139:chemically induced; D013926:Thrombopoietin / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D013997:Time Factors; D014182:Transplantation, Autologous; D014652:Vascular Diseases / Q000139:chemically induced
D011994:Recombinant Proteins; D013501:Surface-Active Agents; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin; D000069585:Filgrastim