Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the study alliance leukemia
Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the study alliance leukemia
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DOI：
10.1038/leu.2015.306
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发表时间：
2016-03-01
期刊：
影响因子：
11.4
通讯作者：
Krug, U.
中科院分区：
文献类型：
--
作者：
Mueller-Tidow, C.;Tschanter, P.;Krug, U.
DNA甲基化改变是急性髓系白血病的一个恒定特征。低甲基化药物如阿扎胞苷作为单一疗法在急性髓性白血病（AML）中具有活性。阿扎胞苷单药治疗无效。AML-AZA试验验证了DNA甲基转移酶抑制剂（如阿扎胞苷）可改善AML化疗结果的假设。这项随机对照试验比较了在每个强化化疗周期前应用阿扎胞苷与单独化疗在老年未经治疗的AML患者中的疗效。无事件生存期（EFS）是主要终点。总共有214例中位年龄为70岁的患者随机接受阿扎胞苷/化疗（A组）或化疗（B组）。A组患者（39/105; 37%）比B组（25/109; 23%）更多显示不良细胞遗传学（P = 0.057）。A组的不良事件发生率（15.44）高于B组的13.52（P = 0.26），但早期死亡率无显著差异（30天死亡率：6% vs 5%，P = 0.76）。两组的中位EFS均为6个月（P = 0.96）。A组患者的中位总生存期为15个月，而B组为21个月（P = 0.35）。阿扎胞苷加标准化疗增加了老年AML患者的毒性，但对AML患者没有额外的益处。
DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P = 0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P = 0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P = 0.76). Median EFS was 6 months in both arms (P = 0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P = 0.35) Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.