Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio 44195, USA.
Cancer. 2011 Mar 1;117(5):992-1000. doi: 10.1002/cncr.25545. Epub 2010 Oct 13.
Romiplostim is a peptibody protein that augments thrombopoiesis by activating the thrombopoietin receptor.
In this phase 2, multicenter, open-label study, 28 thrombocytopenic patients with lower risk myelodysplastic syndromes (MDS) were assigned to receive romiplostim 750 μg administered subcutaneously either weekly or biweekly or administered as biweekly intravenous injections for 8 weeks. Patients also could enter a 1-year study extension phase.
At least 1 adverse event was observed in 93% of patients. The most common adverse events were fatigue and headache (18% for both, and 5 events were grade 3 or 4. There was 1 serious treatment-related adverse event in the biweekly intravenous cohort (hypersensitivity). This hypersensitivity resolved without discontinuation of study treatment. No patients developed neutralizing antibodies or bone marrow fibrosis. Of the patients who completed 8 weeks of treatment, 57% had a complete platelet response, an additional 8% had a major platelet response, and 61% did not require a platelet transfusion during this period. Weekly subcutaneous injections achieved the highest mean trough concentrations.
The safety and efficacy profiles of romiplostim in this study suggested that weekly subcutaneous administration of 750 μg romiplostim is an appropriate starting dose for future clinical studies in patients with MDS and thrombocytopenia.
罗米司亭是一种肽结合蛋白，通过激活血小板生成素受体来增强血小板生成。
在这项 2 期、多中心、开放性研究中，28 例低危骨髓增生异常综合征（MDS）伴血小板减少的患者被分配接受皮下注射罗米司亭 750μg，每周或每两周一次，或每两周静脉注射 8 周。患者也可以进入为期 1 年的研究扩展阶段。
至少有 1 种不良事件发生在 93%的患者中。最常见的不良事件是疲劳和头痛（各占 18%，有 5 例为 3 级或 4 级。在每两周静脉注射组中有 1 例严重的与治疗相关的不良事件（过敏反应）。这种过敏反应无需停止研究治疗即可缓解。没有患者产生中和抗体或骨髓纤维化。在完成 8 周治疗的患者中，57%有完全血小板反应，另有 8%有主要血小板反应，61%在此期间不需要血小板输注。每周皮下注射可达到最高平均谷浓度。
这项研究中罗米司亭的安全性和疗效特征表明，每周皮下注射 750μg 罗米司亭是未来 MDS 和血小板减少症患者临床研究的合适起始剂量。
