Objective: To evaluate the efficacy, safety, and pharmacokinetics of the generic azacitidine in Chinese patients with higher-risk myelodysplastic syndromes(MDS). Methods: Between October 2013 and 2016, 72 patients were eligible for enrollment at 9 sites from China received generic subcutaneous azacitidine 75 mg·m(-2)·d(-1) for 7 days per 28-day cycle, for ≥6 cycles. Pharmacokinetic blood samples were collected on day 1 of a single-dose. Results: For each patient at cycle 6 or at the time of study discontinuation, whichever came first, the overall response rate, which included complete remission (CR)and partial remission(PR), was 6.9%(5/72), the rate of patients who had the best effect with CR or PR during the treatment was 12.5%(9/72). Patients who were dependent on red-blood-cell transfusions and platelet transfusions at baseline became transfusion independent were 46.3%(19/41)and 41.2% (7/17), respectively. The median time of treatment was 6 cycles, and the median OS was 16.1 months (95%CI 10.9-20.6 months). For 36 patients(50%)received treatment at ≥6 cycles, and the median OS was 22.3 months(95%CI 16.1- not evaluative). Most common grade Ⅲ-Ⅳ hematologic treatment-emergent adverse events were neutropenia(55%), leukopenia(47%), and thrombocytopenia(61%). Pharmacokinetic profiles were similar for generic and original azacitidine in Chinese patients. Conclusion: Generic azacitidine treatment was favorable and safe and can be used as a standard treatment for patients with higher-risk MDS.
目的： 评估国产阿扎胞苷治疗较高危骨髓增生异常综合征(myelodysplastic syndromes, MDS)的疗效、安全性及药代动力学特征。 方法： 2013年10月至2016年10月国内10家中心共纳入72例符合入排标准的较高危MDS患者接受国产阿扎胞苷75 mg·m(-2)·d(-1)，皮下注射，持续7 d治疗，4周为1个周期，至少治疗6个周期。药代动力学试验采血为单次给药第1天进行。 结果： 治疗6个周期或6个周期以前终止用药时疗效评估数据显示，总缓解率[完全缓解(CR)+部分缓解(PR)]为6.9%(5/72)，治疗期间最佳疗效为CR或PR的患者比例为12.5%(9/72)。治疗期间脱离红细胞和血小板输血依赖的患者分别为46.3%(19/41)和41.2%(7/17)。72例患者中位治疗时间为6个周期，中位总生存(OS)期16.1(95%CI 10.9~20.6)个月，其中治疗≥6个周期患者36例(50%)，中位OS期22.3(95%CI 16.1~不可评估)个月。治疗中最常见的Ⅲ~Ⅳ级血液学不良事件为中性粒细胞减少(55%)、白细胞减少(47%)和血小板减少(61%)。药代动力学行为和参数与原研中国数据基本一致。 结论： 接受国产阿扎胞苷标准方案治疗疗效肯定，安全可靠，药代动力学参数与原研阿扎胞苷一致，可作为较高危MDS患者的标准治疗药物。.
Keywords: Azacitidine; Clinical trials, phase Ⅲ as topic; Myelodysplastic syndromes; Pharmacokinetics.