药物干预预防抗肿瘤药相关手足综合征的Meta分析

Meta-analysis of Drug Intervention for Preventing Hand-foot Syndrome Caused by Antitumor Drugs

目的:系统评价药物干预预防抗肿瘤药所致手足综合征(HFS)的有效性,并评价结局指标的证据质量,为临床治疗提供参考。方法:计算机检索PubMed、Embase、the Cochrane Library、VIP、WanFang Data和CNKI数据库,搜集药物干预(试验组)和对照组(安慰剂或非药物干预)预防抗肿瘤药相关HFS的随机对照试验(RCT),检索时限均为从建库至2020年2月。两名研究者独立进行文献筛选、数据提取和风险偏倚评价后,采用RevMan 5.3软件进行Meta分析,并采用软件GRADE profile 3.6软件对结果证据质量进行评价。结果:共纳入17个RCT,共计2536例患者。Meta分析结果显示,试验组的HFS的总发生率[OR=0.54,95%CI(0.46,0.64),P<0.00001],1级HFS发生率[OR=0.72,95%CI(0.58,0.90),P=0.004],2级HFS发生率[OR=0.65,95%CI(0.48,0.87),P=0.004]低于对照组,差异均有统计学意义。两组3级HFS发生率的差异无统计学意义[OR=0.66,95%CI(0.42,1.05),P=0.08]。不同干预策略的亚组分析结果显示,维生素E组1级HFS发生率较对照组差异有统计学意义[OR=0.41,95%CI(0.19,0.89),P=0.02];塞来昔布组2级HFS发生率低于对照组,差异有统计学意义[OR=0.38,95%CI(0.18,0.78),P=0.009]。GRADE证据质量评价结果显示,HFS总发生率,1、2、3级HFS发生率均为中级证据质量。结论:药物干预能有效预防抗肿瘤药相关HFS,可降低HFS的总发生率和1级、2级HFS发生率。提示临床可考虑将药物干预作为预防抗肿瘤药相关HFS的选择方案。

Objective:To evaluate the efficacy of drug intervention for preventing hand-foot syndrome(HFS)caused by antitumor drugs and evidence quality,and to provide reference for clinical use.Methods:PubMed,Embase,the Cochrane Library,VIP,WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials(RCTs)about drug intervention(trial group)versus control group for preventing HFS caused by antitumor drugs.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies.RevMan 5.3 software was used for Meta-analysis.GRADE quality of evidence grading system was used to assess the evidence quality of outcome indexes.Results:A total of 17 RCTs involving 2536 patients were included.The results of Meta-analysis showed that the trial group lower than the control group in total incidence of HFS(OR=0.54,95%CI 0.46 to 0.64,P<0.00001),gradeⅠHFS(OR=0.72,95%CI 0.58 to 0.90,P=0.004),gradeⅡHFS(OR=0.65,95%CI 0.48 to 0.87,P=0.004).However,the incidence of gradeⅢHFS in the trial group was not significantly lower than that in the control group(OR=0.66,95%CI 0.42 to 1.05,P=0.08).The subgroup analysis of different intervention strategies for prevention of HFS showed that there was a significant difference in gradeⅠHFS incidence in vitamin E group(OR=0.41,95%CI 0.19 to 0.89,P=0.02);the incidence of HFS in GradeⅡgroup in celecoxib group was lower than that in control group(OR=0.38,95%CI 0.18 to 0.78,P=0.009).Results of grade evidence quality evaluation showed that total incidence of HFS,and the incidence of gradeⅠ/Ⅱ/ⅢHFS were middle,grade by GRADE-quality of evidence system.Conclusion:Drug intervention is effective in preventing HFS caused by antitumor drugs,and can reduce the incidence of total and gradeⅠ/ⅡHFS,which indicates that drug intervention may be considered as an alternative for the prevention of antitumor drugs related HFS.