McElroy Patricia L, Wei Ping, Buck Keri, Sinclair Angus M, Eschenberg Michael, Sasu Barbra, Molineux Graham
Oncology Research Department, Amgen Inc., Thousand Oaks, CA, USA.
Oncology Research Department, Amgen Inc., Thousand Oaks, CA, USA.
Exp Hematol. 2015 Jun;43(6):479-87. doi: 10.1016/j.exphem.2015.02.004. Epub 2015 Mar 6.
Chemotherapy-induced thrombocytopenia can lead to chemotherapy treatment delays or dose reductions. The ability of romiplostim, a thrombopoietin (TPO) mimetic, to promote platelet recovery in a mouse model of multicycle chemotherapy/radiation therapy (CRT)-induced thrombocytopenia was examined. In humans, an inverse relationship between platelet counts and endogenous TPO (eTPO) concentration exists. In a CRT mouse model, eTPO was not elevated during the first 5 days after CRT treatment (the "eTPO gap"), then increased to a peak 10 days after each CRT treatment in an inverse relationship to platelet counts seen in humans. To bridge the eTPO gap, mice were treated with 10-1,000 μg/kg of romiplostim on day 0, 1, or 2 after CRT. In some mice, the romiplostim dose was approximately divided over 3 days. Platelet recovery occurred faster with romiplostim in most conditions tested. Romiplostim doses of ≥100 μg/kg given on day 0 significantly lessened the platelet nadir. Fractionating the dose over 3 days did not appear to confer a large advantage. These data may provide a rationale for clinical studies of romiplostim in chemotherapy-induced thrombocytopenia.
化疗引起的血小板减少症可导致化疗治疗延迟或剂量减少。研究了促血小板生成素（TPO）模拟物罗米司亭在多周期化疗/放疗（CRT）诱导的血小板减少症小鼠模型中促进血小板恢复的能力。在人类中，血小板计数与内源性TPO（eTPO）浓度呈负相关。在CRT小鼠模型中，CRT治疗后的前5天内eTPO未升高（“eTPO间隙”），然后在每次CRT治疗后10天增加至峰值，与人类中观察到的血小板计数呈负相关。为了弥合eTPO间隙，在CRT后的第0、1或2天用10 - 1000μg/kg的罗米司亭治疗小鼠。在一些小鼠中，罗米司亭剂量大约分3天给予。在大多数测试条件下，罗米司亭可使血小板更快恢复。在第0天给予≥100μg/kg的罗米司亭剂量可显著减轻血小板最低点。将剂量分3天给予似乎没有带来很大优势。这些数据可为罗米司亭在化疗引起的血小板减少症中的临床研究提供理论依据。
