重组人血管内皮抑制素联合化疗治疗晚期胃癌近期疗效的Meta分析

Short-term therapeutic effect of recombinant human endostatin combined with chemotherapy for advanced gastric cancer: a Meta-analysis

目的 ：评价重组人血管内皮抑制素（recombinant human endostatin,rhendostatin）联合化疗治疗晚期胃癌的有效性和安全性。方法 ：计算机检索Pub Med、Medline、Cochrane Library、Elsevier、中国生物医学文献数据库（Chinese Bio Medical Literature Database,CBM）、中国知网（China National Knowledge Infrastructure,CNKI）和万方数据库,筛选有关rh-endostatin联合化疗治疗晚期胃癌近期疗效的随机对照试验,检索年限均为从建库至2014年8月。使用修改后的Jadad量表对文献进行评价后提取数据,采用Rev Man 5.2统计软件进行Meta分析,计算相对危险度（relative risk,RR）及95%可信区间（coni dence interval,CI）,采用Stata 12.0统计软件进行Egger检验。结果 ：最终纳入10个随机对照试验,共计623例晚期胃癌患者纳入研究（单纯化疗组308例和rh-endostatin联合化疗组315例）。Meta分析结果显示,与单纯化疗组相比,rh-endostatin联合化疗组的完全缓解（complete response,CR）率（9.21%vs 3.57%,RR=2.24,95%CI：1.21～4.15,P=0.01）、部分缓解（partial response,PR）率（46.35%vs 31.49%,RR=1.47,95%CI：1.21～1.80,P=0.000 1）、总有效率（overall response rate,ORR）（54.60%vs 39.29%,RR=1.39,95%CI：1.17～1.65,P=0.000 2）及临床受益率（clinical benei t rate,CBR）（81.27%vs 69.48%,RR=1.17,95%CI：1.06～1.28,P=0.001 0）均有显著提高;不良反应中的骨髓抑制发生率（61.96%vs 65.10%,RR=0.95,95%CI：0.85～1.07,P=0.42）和胃肠系统不良反应发生率（58.03%vs 57.38%,RR=1.01,95%CI：0.88～1.15,P=0.93）的差异均无统计学意义,rh-endostatin联合化疗组心脏不良反应的发生率较高（12.36%vs 4.19%,RR=2.82,95%CI：1.32～6.00,P=0.007）。结论 ：rh-endostatin联合化疗治疗晚期胃癌的疗效优于单纯化疗,且常见的不良反应未见明显增加,可作为治疗晚期胃癌的常规药物,但应注意rhendostatin可能存在的心脏毒性。

Objective： To evaluate the efficacy and safety of recombinant human endostatin （rh- endostatin） combined with chemotherapy for patients with advanced gastric cancer. Methods： A computer-based online search was performed through PubMed, Medline, Cochrane Library, Elsevier, Chinese BioMedical Literature Database, China National Knowledge Infrastructure （CNKI） and WanFang Database. According to the inclusion and exclusion criteria, the randomized controlled trials about short-term therapeutic effect of rh- endostatin combined with chemotherapy for advanced gastric cancer, which were published up to August 2014, were selected. Quality of the studies was assessed using modified Jadad scale. After data extraction, a Meta-analysis was performed by using RevMan 5.2 software. Relative risk （RR） and its 95% confidence interval （CI） were calculated. The Egger test was performed by using Stata 12.0 software. Results： Ten eligible randomized controlled trials were included in this Meta-analysis including 623 patients （308 in chemotherapy alone group, 315 in rh-endostatin combined with chemotherapy group）. The results showed that there were significant improvements in complete response （CR） rate （9.21% vs 3.57%, RR = 2.24, 95% CI： 1.21-4.15, P = 0.01）, partial response （PR） rate （46.35% vs 31.49%, RR = 1.47, 95% CI： 1.21 -1.80, P = 0.000 1）, overall response rate （ORR） （54.60% vs 39.29%, RR = 1.39, 95% CI： 1.17-1.65, P = 0.000 2） and clinical benefit rate （CBR） （81.27% vs 69.48%, RR = 1.17, 95% CI： 1.06-1.28, P = 0.0010） in rh-endostatin combined with chemotherapy group, as compared with those of the chemotherapy along group. Meanwhile, there were no statistically significant differences in myelosuppression （61.96% vs 65.10%, RR = 0.95, 95% CI： 0.85-1.07, P = 0.42） and gastrointestinal reaction （58.03% vs 57.38%, RR = 1.01, 95% CI： 0.88-1.1 5, P = 0.93）. However, the rate of cardiotoxicity was higher in rh-endostatin combined with chemotherapy group （12.36% vs 4.19%, RR = 2.82, 95% CI： 1.32-6.00, P= 0.007）. Conclusion： This Meta-analysis indicates that in comparison with chemotherapy alone, rh- endostatin combined with chemotherapy has better therapeutic effect on advanced gastric cancer and the common adverse events do not increase. Therefore, rh-endostatin can be used as a routine drug for advanced gastric cancer. Meanwhile, it also increases the rate of cardiotoxicity, and more attention should be paid to this problem.