一项关于阿扎胞苷和阿糖胞苷联合治疗急性髓系白血病和高危骨髓增生异常综合征的 1/2 期研究报告。
Report of a phase 1/2 study of a combination of azacitidine and cytarabine in acute myelogenous leukemia and high-risk myelodysplastic syndromes.
机构信息
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Leuk Lymphoma. 2010 Jan;51(1):73-8. doi: 10.3109/10428190903318329.
Abstract
Cytarabine resistance characterizes relapsed and refractory acute myelogenous leukemia (AML). Restoration of cytarabine sensitivity can potentially improve treatment outcome in this setting. Acquired hypermethylation of gene promoters and associated silencing of gene expression has been implicated in chemo resistance, and drug-induced hypomethylation can improve sensitivity to cytarabine in vitro. We conducted an adaptively randomized study of a combination of azacitidine, a hypomethylating agent, and cytarabine in 34 patients with AML. The combination administered in a concomitant fashion is safe at full doses of azacitidine and cytarabine, without unexpected toxicities. However, in this advanced AML population, it was difficult to deliver more than one cycle of therapy, and minimal anti-leukemia activity was seen in patients with relapsed/refractory disease. Complete remission was achieved in 2 of 6 minimally pre-treated patients. We conclude that the combination of azacitidine and cytarabine is feasible but has limited activity in relapsed/refractory AML.
摘要
阿扎胞苷联合阿糖胞苷治疗复发性难治性急性髓系白血病的研究
阿糖胞苷耐药是复发性难治性急性髓系白血病（AML）的特征。恢复阿糖胞苷敏感性可能会改善这种情况下的治疗效果。基因启动子的获得性高甲基化及其相关的基因表达沉默与化疗耐药有关，而药物诱导的低甲基化可以提高阿糖胞苷在体外的敏感性。我们对 34 例 AML 患者进行了阿扎胞苷（一种低甲基化药物）联合阿糖胞苷的适应性随机研究。联合用药以全剂量阿扎胞苷和阿糖胞苷同时给药是安全的，没有意外的毒性。然而，在这个晚期 AML 患者人群中，很难完成一个以上周期的治疗，并且在复发性/难治性疾病患者中观察到的抗白血病活性很小。6 例预处理较少的患者中有 2 例达到完全缓解。我们的结论是，阿扎胞苷联合阿糖胞苷是可行的，但在复发性/难治性 AML 中的活性有限。
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