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

被引:29
作者
Bolwell, B
Vredenburgh, J
Overmoyer, B
Gilbert, C
Chap, L
Menchaca, DM
Cruickshank, S
Glaspy, J
机构
[1] Cleveland Clin Fdn, Cleveland, OH 44195 USA
[2] Duke Univ, Med Ctr, Durham, NC USA
[3] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA
[4] Amgen Inc, Thousand Oaks, CA 91320 USA
关键词
breast cancer; clinical trial; engraftment; PEG-rHuMGDF; peripheral blood progenitor cell transplantation; platelet;
D O I
10.1038/sj.bmt.1702465
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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.
引用
收藏
页码:141 / 145
页数:5
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