雷替曲塞治疗晚期胃癌临床疗效的 Meta 分析

Meta-analysis of the therapeutic effect of raltitrexed on advanced gastric cancer

目的：总结国内外雷替曲塞治疗晚期胃癌的研究结果，评价雷替曲塞治疗晚期胃癌的临床疗效及不良反应。方法检索 PubMed、EMBase、Ovid、Springer、万方医药期刊全文数据库、维普中文科技期刊全文数据库、中国生物医学文献数据库，此外手工检索重要文献的参考文献、会议专题，查找雷替曲塞对比其他化疗药物治疗晚期胃癌的对照临床试验。按纳入排除标准选择文献，提取数据，利用RevMan 4.2软件进行 Meta 分析。结果共检索出44篇文献，最终纳入5篇对照研究，共338例患者。Meta 分析结果显示，雷替曲塞组客观有效率明显高于其他化疗药物组（RR ＝1.55，95％ CI：1.21～1.99， Z ＝3.44，P ＝0.00）。关于Ⅲ～Ⅳ级不良反应，雷替曲塞组中性粒细胞减少（RR ＝1.97，95％ CI：0.85～4.56，Z ＝1.59，P ＝0.11）、血小板减少（RR ＝1.56，95％ CI：0.60～4.07，Z ＝0.92，P ＝0.36）、贫血（RR ＝2.43，95％ CI：0.61～9.78，Z ＝1.25，P ＝0.21）、关节痛（RR ＝3.20，95％ CI：0.73～13.98，Z ＝1.55，P ＝0.12）、转氨酶升高（RR ＝1.37，95％ CI：0.29～6.48，Z ＝0.39，P ＝0.69）等不良反应发生率较高，但差异均无统计学意义；而腹泻（RR ＝0.18，95％ CI：0.03～1.07，Z ＝1.88，P ＝0.06）、恶心呕吐（RR ＝0.45，95％ CI：0.19～1.08，Z ＝1.79，P ＝0.07）、神经毒性（RR ＝0.07，95％ CI：0.01～0.52，Z ＝2.59，P ＝0.01）、手足综合征（ RR ＝0.26，95％ CI：0.04～1.59，Z ＝1.46，P ＝0.14）、脱发（ RR ＝0.57，95％ CI：0.13～2.55，Z ＝0.73，P ＝0.46）等不良反应发生率较低，除神经毒性外，差异均无统计学意义。结论雷替曲塞治疗晚期胃癌疗效优于其他化疗方案，且不良反应轻，值得临床推广使用。

Objective To summarize the research results at home and abroad of raltitrexed on the patients with advanced gastric cancer,and to evaluate the clinical efficacy and adverse reactions of raltitrexed. Methods Clinical controlled trials of evaluating effects of raltitrexed on the advanced gastric cancer were searched in PubMed,EMBase,Ovid,Springer,Wanfang database,VIP database and China Biology Medicine disc. Besides,references and conference abstracts were searched manually. Literature screening and data extraction were performed according to inclusion and exclusion criteria. Then Meta-analysis was performed using RevMan 4. 2. Results Forty-four studies were found and 5 clinical controlled trails including 338 patients were included in this analysis. The results of Meta-analysis showed that there was a significant beneficial effect of raltitrexed on objective effective rate for the patients with advanced gastric cancer（RR = 1. 55,95% CI：1. 21-1. 99,Z = 3. 44,P = 0. 00）compared with other treatments. The incidences of Ⅲ-Ⅳadverse reactions in raltit-rexed group such as neutropenia（RR = 1. 97,95% CI：0. 85-4. 56,Z = 1. 59,P = 0. 11）,thrombocytopenia （RR = 1. 56,95% CI：0. 60-4. 07,Z = 0. 92,P = 0. 36）,anemia（RR = 2. 43,95% CI：0. 61-9. 78,Z =1. 25,P = 0. 21）,arthralgia（RR = 3. 20,95% CI：0. 73-13. 98,Z = 1. 55,P = 0. 12）,elevated transaminase （RR = 1. 37,95% CI：0. 29-6. 48,Z = 0. 39,P = 0. 69）were higher than those in other group,with no statis-tical significance. However,the adverse reactions in raltitrexed group such as diarrhea（RR = 0. 18,95% CI：0. 03-1. 07,Z = 1. 88,P = 0. 06）,nausea and vomiting（Z = 1. 79,RR = 0. 45,95% CI：0. 19-1. 08,P =0. 07）,neurotoxicity（RR = 0. 07,95% CI：0. 01-0. 52,Z = 2. 59,P = 0. 01）,hand-foot syndrome（RR =0. 26,95% CI：0. 04-1. 59,Z = 1. 46,P = 0. 14）,alopecia（RR = 0. 57,95% CI：0. 13-2. 55,Z = 0. 73, P = 0. 46）were lower than those in other group. There were no statistical significances except neurotoxicity. Conclusion Compared with other treatments,raltitrexed-based chemotherapy has a beneficial effect on objective effective rate and less adverse reactions for the patients with advanced gastric cancer,which is worthy of clinical use.