三氧化二砷与全反式维甲酸治疗急性早幼粒细胞白血病疗效比较的系统评价

目的 比较三氧化二砷(arsenic trioxide,ATO)与全反式维甲酸(all-trans retinoic acid,ATRA)治疗急性早幼粒细胞白血病(acute promyeloeytic leukemua,APL)的疗效与安全性.方法 采用Cochrane系统评价方法,检索Cochrane图书馆及其临床对照试验数据库、MEDLINE、EMBASE、CBM、CNKI和CMAC,并辅以手工检索,检索时间截至2009年3月.获取比较ATO和ATRA治疗APL疗效的随机对照试验文献,以完全缓解率、总生存率、无病生存率、治疗开始到获得缓解的时间、复发率、病死率及治疗相关副反应为结局评价指标,使用Cochrane协作网Revman 5.0软件进行Meta分析.结果 共鉴定并纳入4项随机对照试验研究(RCT),共包括243例APL患者,研究的偏倚风险评估全部为中等程度偏倚,研究目的均为比较ATO与ATRA治疗APL的疗效和副反应发生情况.Meta分析结果显示,ATO与ATRA治疗初治APL比较,针对CR、复发率、病死率等结局指标差异尤统计学意义(P>0.05),以上各结局指标的比值比(OR)及其95%C1分别为0.96(0.50～1.86)、0.86(0.45～1.63)和1.15(0.45～2.95);开始治疗到获得CR的时间结局指标差异无统计学意义(P>0.05),均数差值及其95%CI为0.60 d(-12.34～13.53);无病生存率的比较差异也无统计学意义(P>0.05),风险比率(HR)及其95%CI为2.76(0.71～10.66).针对肝功能异常发生率结局指标比较的OR及其95%CI为3.03(1.25～7.37),差异有统计学意义(P=0.01).结论 Meta分析结果提示,采用ATO治疗初治APL患者与ATRA疗效相当,但ATO可能导致肝功能异常的发生率增加.

Arsenic trioxide vs all-trans retinoic acid to treat acute promyelocytic leukemia: a systematic comparative review

Objective To compare the efficacy and safety of arsenic trioxide ( ATO) with all-trans retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia ( APL). Methods We searched the database of Cochrane Library (Issue 1, 2009), CENTRAL (1970 to 2009), Medline (1978 to 2008), EMBASE (1950 to 2009) , CBM (1978 to 2008) , CNKI (1994 to 2008) and CMAC (1994 to 2008). We also searched the Meta register, Conference Proceedings of American Society of Hematology (1946 to 2008) and American Society of Clinical Oncology (2004 to 2008) on the internet for grey literature. We had searched the related journals in the library of Third Military Medical University, too. We included randomized controlled trials which compared ATO with ATRA for the treatment of APL. We adopt complete remission rate, overall survival rate, disease-free survival rate, time to complete remission, relapse rate, mortality and adverse reactions as result indicators. Data were entered and analyzed with the Cochrane review manager software ( Revman 5.0). Results Four eligible randomized controlled trials (RCTs) were included (n =243). All the RCTs were meth-odologically graded as B. They all are focusing on the comparison of ATO monotherapy with ATRA monotherapy in treating newly diagnosed APL patients. Meta analysis showed that effect index for complete remission, 2-year disease-free survival, time to complete remission, relapse rate and mortality was 0. 96 (0. 50, 1. 86) , 2. 76 (0.71,10.66), -1.30 d (-1.83, -0.78), 0.86 (0.45, 1.63), and 1.15 (0.45, 2.95), respectively. All indicated no statistically significant difference. Effect index for incidence of liver dysfunction was 3.03 ( 1.25 , 7.37) , which showed statistically significant difference between ATO group and ATRA group. Conclusion ATO is not superior to ATRA in treating newly diagnosed APL patients regarding complete remission, disease-free survival rate, time to complete remission, relapse rate and mortality. What is worse, it will increase the in-cidence of liver dysfunction during treatment. Due to limitation of included trials, this conclusion need to be validated by further studies.