Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia
Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia
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DOI：
10.1182/blood-2006-05-021162
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发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Issa, Jean-Pierre J.
中科院分区：
文献类型：
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作者：
Kantarjian, Hagop;Oki, Yasuhiro;Issa, Jean-Pierre J.
低甲基化药物的表观遗传治疗现在是骨髓增生异常综合征（MDS）的标准治疗方法。反应率仍然很低，基于机制的剂量优化尚未报道。我们研究了地西他滨不同剂量方案的临床和药效学结果。患有晚期MDS或慢性髓细胞白血病（CMML）的成人随机分配到三种地西他滨方案中的一种：(1)每天静脉注射20mg /m，持续5天；(2)每日皮下注射20mg /m，连续5天；(3)每日静脉滴注10mg /m，连用10天。随机化遵循贝叶斯自适应设计。95例患者接受治疗（77例MDS， 18例CMML）。总体而言，32名患者（34%）达到完全缓解（CR）， 69名患者（73%）根据新修订的国际工作组标准获得客观缓解。选择剂量强度最高的5 d静脉注射方案为最优方案；该组的CR率为39%，而5天皮下组为21%，10天静脉组为24%
Epigenetic therapy with hypomethylating drugs is now the standard of care in myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based dose optimization has not been reported. We investigated the clinical and pharmacodynamic results of different dose schedules of decitabine. Adults with advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m(2) intravenously daily for 5 days; (2) 20 mg/m(2) subcutaneously daily for 5 days; and (3) 10 mg/m(2) intravenously daily for 10 days. Randomization followed a Bayesian adaptive design. Ninety-five patients were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved a complete response (CR), and 69 (73%) had an objective response by the new modified International Working Group criteria. The 5-day intravenous schedule, which had the highest dose-intensity, was selected as optimal; the CR rate in that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the 10-day intravenous arm (P