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 (II = 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 mu g/kg/day) (n = 34), Blinded study drug was started on the day of transplantation and was continued until the platelet count was greater than or equal to 100 x 10(9)/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 II 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 mu g/kg group) probably related to study drug, and veno-occlusive disease (VOD) (in the 5 mu g/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 10(9)/l and 299 vs 145 x 10(9)/l, respectively; both P < 0.05), PEG-rHuMGDF up to 10 mu g/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.