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 aut ologous peripheral blood progenitor cell (PBPC) transplantation were random ized to placebo (II = 13) or to one of five sequential dose cohorts of pegy lated (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 st udy 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 pat ients received filgrastim starting on day +2 after transplantation. The nad ir platelet count was not affected by treatment. The median time to platele t recovery was II and 12 days for the placebo and combined PEG-rHuMGDF grou ps, respectively. No trends in adverse events suggested dose- or treatment- related toxicity. Two patients withdrew from the study because of an advers e event (allergic reaction in the 7.5 mu g/kg group) probably related to st udy drug, and veno-occlusive disease (VOD) (in the 5 mu g/kg group) which w as felt not to be related to study drug by the investigator. No patients de veloped neutralizing antibodies to MGDF. Day +21 and day +28 platelet count s 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 d rug on initial platelet engraftment at the doses studied. However, the effi cacy of other doses is unknown.