阿帕替尼联合替吉奥治疗晚期胃癌的疗效及安全性的Meta分析

目的:总结阿帕替尼联合替吉奥治疗晚期胃癌的疗效及安全性，以期为临床提供更多的循证医学证据。方法:通过计算机文献检索中英文数据库，收集国内外公开发表的阿帕替尼联合替吉奥（试验组）对比替吉奥（对照组）治疗晚期胃癌的随机对照试验，检索时间截止于2019年8月21日，由两名研究者独立地筛选文献、提取资料并使用Cochrane风险偏倚评估工具评价文献质量后，主要采用Review Manager 5.3软件进行Meta分析。结果:共纳入20篇文献，合计1 150名患者。Meta分析结果显示，阿帕替尼联合替吉奥组患者客观缓解率［OR=2.02，95%CI（1.56，2.63），P<0.000 01］、疾病控制率［OR=3.10，95%CI（2.30，4.17），P<0.000 01］、中位总生存期［MD=3.99，95%CI（3.56，4.43），P<0.000 01］均高于替吉奥组，两者中位无进展生存期无显著性差异［MD=1.24，95%CI（-1.19，3.67），P=0.32］，不良反应中仅阿帕替尼联合替吉奥组的高血压发生率［OR=6.19，95%CI（1.89，20.23），P=0.003］及蛋白尿发生率［OR=4.02，95%CI（1.11，14.62），P=0.03］高于替吉奥组，其余不良反应间亦无显著性差异，另外阿帕替尼联合替吉奥组的IFN-γ、TNF-α水平高于替吉奥组，IL-10、IL-4、TSGF、CA199、CEA水平则低于替吉奥组。结论:当前证据显示，阿帕替尼联合替吉奥较单药替吉奥可获得更高的客观缓解率、疾病控制率、中位总生存期，不良反应较少，免疫功能有所提高，能有效降低肿瘤标志物水平。但受纳入研究数量及质量的限制，上述结论尚需开展更多高质量研究予以验证。

Meta-analysis of the efficacy and safety of apatinib combined with S-1 in the treatment of advanced gastric cancer

Objective:To study the efficacy and safety of apatinib combined with S-1 in the treatment of advanced gastric cancer，in order to provide more evidence-based medical evidence for the clinic.Methods:Randomized controlled trials of apatinib combined with S-1 (experimental group) versus S-1 (control group) in the treatment of advanced gastric cancer were collected by computer literature search in Chinese and English databases，for the deadlines of August 21，2019.Two investigators independently screened the literature，extracted the data，and evaluated the quality of the literature using the Cochrane risk bias assessment tool.And the Meta-analysis was performed using Review Manager 5.3 software almost.Results:A total of 20 articles were included，totaling 1 150 patients.Meta-analysis showed that the objective response rate［OR=2.02，95%CI(1.56，2.63)，P<0.000 01］，disease control rate ［OR=3.10，95%CI(2.30，4.17)，P<0.000 01］，median overall survival ［MD=3.99，95%CI(3.56，4.43)，P<0.000 01］of patients with apatinib combined with S-1 group were higher than the S-1 group，then the median progression-free survival had not significant differences ［MD=1.24，95%CI(-1.19，3.67)，P=0.32］.In the adverse reactions，only the incidence of hypertension ［OR=6.19，95%CI(1.89，20.23)，P=0.003］ and the incidence of proteinuria ［OR=4.02，95%CI(1.11，14.62)，P=0.03］ in the apatinib combined with S-1 group were higher than the S-1 group，and there was no significant difference in the other adverse reactions.In addition，the levels of IFN-γ and TNF-α in the apatinib combined with S-1 group were higher than those in the S-1 group，and the levels of IL-10，IL-4，TSGF，CA199 and CEA were lower than those of the S-1 group.Conclusion:Current evidence suggests that apatinib combined with S-1 can achieve higher objective response rate，disease control rate，median overall survival，less adverse reactions，and improve immune function，effectively reduce the level of tumor markers.However，due to the limitations of the quantity and quality of the research，the above conclusions need to be verified by more high-quality studies.