Shapiro Roman M, Lazo-Langner Alejandro
1Department of Medicine, Western University, London, ON Canada.
2Department of Medicine, Division of Hematology, Western University, London, ON Canada.
BMC Hematol. 2018 Jan 31;18:3. doi: 10.1186/s12878-017-0094-8. eCollection 2018.
5-Azacitidine administered as a 7-day dosing regimen (7-0-0) is approved in high risk IPSS myelodysplastic syndrome (MDS) patients. Alternative regimens such as a 5-day (5-0-0) or 7-day with a weekend break (5-2-2) are commonly used. No randomized controlled trial has been done directly comparing all three dosing regimens. The objective of this study was to compare the efficacies of the 5-0-0, 5-2-2, and 7-0-0 regimens in MDS and AML.
A systematic review was conducted using MEDLINE, EMBASE and CENTRAL. Eligible studies were randomized controlled trials (RCTs), observational prospective and retrospective studies. The primary clinical outcomes were Objective Response Rate (ORR) defined as the sum of complete response (CR), partial response (PR), and hematological improvement (HI) as defined by the IWG 2006 criteria. A meta-analysis of simple proportions was conducted using a random effects model with weights defined according to Laird and Mosteller. Comparisons between groups were not attempted due to the heterogeneity of study designs.
The only RCT directly comparing alternative azacitidine regimens showed no difference in ORR between the 5-0-0 and 5-2-2 regimens. All other RCTs compared a dosing regimen to conventional care. The pooled proportion of ORR was 44.8% with 95% CI (42.8%, 45.5%) for 7-0-0, 41.2% with 95% CI (39.2%, 41.9%) for 5-0-0, and 45.8% with 95% CI (42.6%, 46.4%) for 5-2-2.
Indirect comparison of alternative azacitidine dosing regimens in MDS and AML shows a benefit for the 7-day regimen in attaining ORR. Additional RCTs are required to definitively address this comparison.
5-氮杂胞苷以7天给药方案（7-0-0）给药已被批准用于高危国际预后评分系统（IPSS）骨髓增生异常综合征（MDS）患者。常用的替代方案如5天（5-0-0）或7天且周末休息（5-2-2）方案。尚未进行直接比较所有这三种给药方案的随机对照试验。本研究的目的是比较5-0-0、5-2-2和7-0-0方案在MDS和急性髓系白血病（AML）中的疗效。
使用MEDLINE、EMBASE和CENTRAL进行系统评价。符合条件的研究为随机对照试验（RCT）、观察性前瞻性和回顾性研究。主要临床结局为客观缓解率（ORR），根据国际工作组（IWG）2006标准定义为完全缓解（CR）、部分缓解（PR）和血液学改善（HI）之和。使用随机效应模型对简单比例进行荟萃分析，权重根据莱尔德和莫斯特勒定义。由于研究设计的异质性，未尝试进行组间比较。
唯一直接比较替代阿扎胞苷方案的RCT显示，5-0-0和5-2-2方案之间的ORR无差异。所有其他RCT将一种给药方案与传统治疗进行了比较。7-0-0方案的ORR合并比例为44.8%，95%可信区间（CI）为（42.8%，45.5%）；5-0-0方案为41.2%，95%CI为（39.2%，41.9%）；5-2-2方案为45.8%，95%CI为（42.6%，46.4%）。
MDS和AML中替代阿扎胞苷给药方案的间接比较显示，7天方案在达到ORR方面具有优势。需要更多的RCT来明确解决这一比较问题。
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