Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia
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DOI：
10.1200/jco.2011.38.9429
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发表时间：
2012-07-20
影响因子：
45.3
通讯作者：
Arthur, Christopher
中科院分区：
文献类型：
--
作者：
Kantarjian, Hagop M.;Thomas, Xavier G.;Arthur, Christopher
目的：这项多中心、随机、开放标签的III期临床试验比较了地西他滨与治疗选择（TC）在老年新诊断急性髓系白血病（AML）和低或中危细胞遗传学患者中的疗效和安全性。患者和方法年龄bb0 = 65岁的患者（N = 485）随机分配为1∶1组，接受地西他滨20 mg/m(2) /天静脉滴注1小时，每4周连续5天；或TC（支持治疗或阿糖胞苷20 mg/m(2) /天皮下注射，每4周连续10天）。主要终点为总生存期（OS）；次要终点为完全缓解（CR）率加无血小板恢复（CRp）的CR率。记录不良事件（ae）。结果396例死亡（81.6%）的初步分析显示，地西他滨组的中位总生存期（7.7个月，95% CI, 6.2 ~ 9.2）较TC组（5.0个月，95% CI, 4.3 ~ 6.3; P = 0.108；危险比[HR]， 0.85; 95% CI, 0.69 ~ 1.04）无显著增加。一项有446例死亡（92%）的非计划分析显示相同的中位总生存期（HR, 0.82; 95% CI， 0.68至0.99；名义P = 0.037）。地西他滨组CR + CRp为17.8%，TC组为7.8%（优势比为2.5；95% CI为1.4 ~ 4.8;P = 0.001）。地西他滨和阿糖胞苷的ae相似，尽管患者接受地西他滨的中位数为4个周期，而TC为2个周期。地西他滨最常见的药物相关ae是血小板减少症（27%）和中性粒细胞减少症（24%）。结论在老年AML患者中，与标准治疗相比，地西他滨提高了应答率，但在安全性方面没有重大差异。计划外生存分析显示地西他滨有益处，这在初步分析时没有观察到。
PurposeThis multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics.Patients and MethodsPatients (N = 485) age >= 65 years were randomly assigned 1: 1 to receive decitabine 20 mg/m(2) per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m(2) per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded.ResultsThe primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%).ConclusionIn older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis.