A Phase 1 Trial of Eltrombopag in Patients Undergoing Stem Cell Transplantation after Total Body Irradiation
详细信息 查看全文
- 作者：Jane L. Liesveld ; Gordon L. Phillips II ; Michael Becker ; Louis S. Constine ; Jonathan Friedberg ; Jeffrey R. Andolina ; Laurie A. Milner ; Jessica DeBolt ; Therese Smudzin ; Ollivier Hyrien ; Connie L. Erickson-Miller ; Brendan M. Johnson ; Katie-Louise Dawson ; Yuhchyau Chen
- 关键词：Thrombopoietin mimetic ; Bone marrow engraftment ; Radiation ; Pharmacokinetics ; Platelet ; Thrombocytopenia
- 刊名：Biology of Blood and Marrow Transplantation
- 出版年：December, 2013
- 年：2013
- 卷：19
- 期：12
- 页码：1745-1752
- 全文大小：569 K
文摘
Stem cell transplantation can be associated with significant periods of thrombocytopenia, necessitating platelet transfusions and contributing to the risk of bleeding. Thrombopoietin receptor agonists have been shown to enhance platelet counts in other clinical settings, and so a phase 1 clinical trial was conducted to assess the safety, pharmacokinetics, and maximum tolerated dose of once-daily eltrombopag in patients undergoing stem cell transplantation with conditioning regimens containing total body irradiation 鈮?00 cGy. Eltrombopag was examined at dosage levels of 75, 150, 225, and 300 mg given orally once daily for 27 days, starting at 24 to 48 hours post-transplantation. Pharmacokinetic sampling was performed over a 24-hour period after the first dose of eltrombopag, as well as during the second week of treatment (steady-state). Nineteen patients were enrolled, 15 of whom completed protocol treatments. Three patients completed each dose level up to 225 mg, and 6 completed treatment at the highest dose of 300 mg. Four patients were replaced because drug compliance was <75% of planned doses. No dose-limiting toxicities were observed in this heterogeneous post-transplantation patient population. Common adverse events were related to standard stem cell transplantation. One episode of pulmonary embolus occurred 9 days after discontinuation of eltrombopag, and the only other thromboembolic episode was a grade 2 catheter-related clot. We conclude that up to 27 days of once-daily dosing of eltrombopag after stem cell transplantation is well tolerated.