贝伐单抗联合化疗一线治疗转移性结直肠癌有效性和安全性的系统评价

Bevacizumab plus chemotherapy as first-line therapy for metastatic colorectal cancer:a systematic review of the efficacy and safety

目的：系统评价贝伐单抗（bevacizumab,BEV）联合化疗一线治疗转移性结直肠癌的有效性和安全性。方法：利用计算机检索PubMed、Embase、Cochrane图书馆、中国期刊全文数据库、中国生物医学文献数据库和中文科技期刊全文数据库中的BEV联合化疗一线治疗转移性结直肠癌的随机对照试验,对纳入研究的方法学质量进行评价,并进行荟萃分析。结果：共纳入6篇文献,包括2 646名患者。荟萃分析结果显示,BEV联合化疗组的有效率（完全缓解＋部分缓解）较高（相对危险度为1.27,95%的可信区间为1.00～1.61,P=0.05）,且中位生存时间和无进展生存（progression-free survival,PFS）时间延长。治疗组与对照组总的3/4级不良反应、3/4级高血压、不良反应所致研究中止以及胃肠穿孔发生率的差异均有统计学意义,其相对危险度（95%的可信区间）分别为1.12（1.07～1.61）、4.51（2.81～7.23）、1.37（1.16～1.63）和4.32（1.24～15.05）;而3/4级出血、60 d全因死亡率、3/4级蛋白尿、3/4级腹泻、3/4级白细胞减少和肺栓塞的发生率差异则无统计学意义,其相对危险度（95%的可信区间）分别为1.50（0.87～2.57）、0.71（0.45～1.11）、2.26（0.69～7.33）、1.18（0.99～1.41）、1.17（0.97～1.42）和0.84（0.46～1.53）。结论：BEV联合化疗一线治疗转移性结直肠癌可提高有效率,延长PFS和中位生存时间,但总的3/4级不良反应、3/4级高血压和胃肠穿孔的发生率较高。

Objective：To systematically assess the efficacy and safety of bevacizumab（BEV） plus chemotherapeutic agents as first-line therapy for metastatic colorectal cancer（mCRC）.Methods：We retrieved randomized controlled clinical trials（RCTs） of BEV plus chemotherapeutic agents as first-line therapy for mCRC from the databases of PubMed（1966 to August 2009）,Embase（1974 to August 2009）,Cochrane Library（Issue 3,2009）,China Journal Full Text Database（CJFD,1994 to August 2009）,Chinese Bio-medical Literature Database（CBM,1978 to August 2009） and Chinese Scientific Journals Full Text Database（CSJD,1989 to August 2009）.Then we evaluated the methodological quality of included studies.Meta-analysis was performed using RevMan 5.0 software developed by the Cochrane Collaboration.Results：Only 6 clinical studies were selected and 2 646 eligible patients were included in the systematic review.Meta-analysis showed that BEV plus chemotherapy increased the overall response rate（complete response＋partial response） compared with chemotherapy alone.The relative risk was 1.27（95%CI： 1.00-1.61,P=0.05）,and the median survival time and progression-free survival（PFS） were longer.In terms of safety,there was a significant difference in the frequency of grade 3/4 adverse events,grade 3/4 hypertension,adverse events-induced study discontinuation and gastrointestinal perforation between the two groups.The relative risk was 1.12（95%CI： 1.07-1.61）,4.51（95%CI： 2.81-7.23）,1.37（95%CI： 1.16-1.63）and 4.32（95% CI：1.24-15.05）,respectively.There was no statistical difference between the two groups in the incidence of grade 3/4 bleeding,60-day all-cause mortality,grade 3/4 proteinuria,grade 3/4 diarrhea,grade 3/4 leukopenia and pulmonary embolism.The relative risk was 1.50（95%CI： 0.87-2.57）,0.71（95%CI： 0.45-1.11）,2.26（95%CI： 0.69-7.33）,1.18（95%CI： 0.99-1.41）,1.17（95%CI： 0.97-1.42）and 0.84（95%CI： 0.46-1.53）,respectively.Conclusion：BEV plus chemotherapeutic agents as first-line the-rapy increases the response rate and prolongs PFS and median survival time of mCRC patients,but results in a higher incidence of any grade 3/4 adverse event,grade 3/4 hypertension and gastrointestinal perforation.