抗血管生成药物治疗晚期肾癌疗效的Meta分析

Meta-analysis of Anti-Vascular Endothelial Growth Factor Agents Therapy for Advanced Renal Cell Carcinoma

目的系统评价干扰素和靶向血管内皮生长因子(VEGF)抗血管生成药物(索拉非尼、舒尼替尼和贝伐单抗)治疗晚期肾癌的疗效。方法计算机检索MEDLINE、EMbase、中国生物医学期刊文献数据库、中文科技期刊数据库,收集1979～2009年国内外公开发表的抗血管生成药物与干扰素比较的随机对照试验。按Cochrane系统评价方法评价纳入研究质量和提取有效数据,并用RevMan4.2软件进行Meta分析。结果最终纳入4个随机对照试验,共2320例。Meta分析结果显示:①与干扰素相比,血管生成抑制剂单用能有效抑制晚期肾癌进展[OR=0.38,95%CI(0.29,0.51),P<0.01]和控制晚期肾癌[OR=2.53,95%CI(1.87,3.43),P<0.01],但两者对治疗肾癌的总有效率差异无统计学意义[OR=1.97,95%CI(0.20,19.57),P=0.56];②与单用干扰素相比,血管生成抑制剂联合干扰素能有效抑制晚期肾癌进展[OR=0.67,95%CI(0.53,0.84),P=0.0005]和控制晚期肾癌[OR=2.14,95%CI(1.65,2.78),P<0.01],显著提高晚期肾癌治疗的总有效率[OR=2.65,95%CI(1.94,3.61),P<0.01];③血管生成抑制剂与干扰素各自单用治疗发生严重不良事件的可能性相当[OR=1.98,95%CI(0.90,4.34),P=0.09],但二者联用更易发生严重不良事件[OR=2.63,95%CI(2.09,3.31),P<0.01]。结论与干扰素相比,血管生成抑制剂单用能更有效抑制肿瘤进展,控制晚期肾癌;血管生成抑制剂与干扰素联用能显著提高肿瘤治疗总有效率,但也伴随着更多药物相关严重不良事件的发生。

Objective To evaluate the efficacy and safety of anti-vascular endothelial growth factor（VEGF） agents for advanced renal cell carcinoma.Methods We searched MEDLINE,EMbase,The Cochrane Library,CBMdisc and China Academic Periodical database from the establishment of each database to April 2009.We included randomized controlled trials（RCTs） that evaluated anti-VEGF agents（sunitinib,sorafenib and bevacizumab）.The quality of the included trials was evaluated by two reviewers independently.Meta-analyses were conducted by the Cochrane Collaboration＇s RevMan 4.2 software.Results Four RCTs involving 2 320 patients were identified.According to the different interventions for advanced renal cell carcinoma,we divided the patients into two groups：anti-VEGF agents monotherapy and anti-VEGF agents plus interferon combination treatment.Our meta-analyses showed：monotherapy was superior to interferon on inhibition of tumor progression [OR=0.38,95%CI（0.29,0.51）,P〈0.01] and control of tumor [OR=2.53,95%CI（1.87,3.43）,P〈0.01],but was not significantly different from interferon on the overall effective rate [OR=1.97,95%CI（0.20,19.57）,P=0.56] and serious side effects [OR=1.98,95%CI（0.90,4.34）,P=0.09].There were significant differences between anti-VEGF agents plus interferon and interferon alone on inhibition of tumor progression [OR=0.67,95%CI（0.53,0.84）,P=0.000 5],overall effective rate [OR=2.65,95%CI（1.94,3.61）,P〈0.01],control of tumor [OR=2.14,95%CI（1.65,2.78）,P〈0.01] and serious side effects [OR=2.63,95%CI（2.09,3.31）,P〈0.01].Conclusion Compared with interferon,anti-VEGF agents could inhibit tumor progression more effectively.Moreover,the combination therapy with interferon could offer a more favorable overall effective rate for advanced renal cell carcinoma,but then followed by more serious side effects.We need to weigh the merits and demerits of drugs before making a clinical decision for advanced renal cell carcinoma.