阿帕替尼对晚期实体恶性肿瘤疗效和安全性Meta分析

Meta-analysis of the effectiveness and safety of Apatinib for advanced solid malignant tumor

目的系统评价阿帕替尼用于进展期胃癌(advanced gastric cancer,AGC)、非小细胞肺癌(non-small cell lung cancer,NSCLC)、肝细胞肝癌(hepatocellular carcinoma,HCC)、卵巢癌(ovarian cancer,OC)、结肠癌(colon cancer,CC)和前列腺癌(prostate cancer,PCa)等晚期实体恶性肿瘤的疗效和安全性,为临床用药提供参考。方法计算机检索Cochrane图书馆、PubMed、中文科技期刊数据库(China Science and Technology Journal Database,CSTJ)、中国生物医学文献数据库(China Biology Medicine disc,CBMdisc)、中国知网(China National Knowledge Infrastructure,CNKI)和万方医学网,收集阿帕替尼与常规治疗对晚期实体恶性肿瘤治疗的随机对照试验,分别按照Cochrane手册偏倚性评估表和修改后的Jadad评分量表评价纳入研究文献质量,提取相关资料,采用RevMan 5.3进行Meta分析。结果共纳入36项随机对照研究,合计2 469例患者。与对照组相比,阿帕替尼显著提高患者客观缓解率(objective response rate,ORR;RR=1.45,95%CI为1.29~1.62,P<0.001)和疾病控制率(disease control rate,DCR;RR=1.24.95%CI为1.12~1.37,P<0.001);降低患者血清血管内皮生长因子(vascular endothelial growth factor,VEGF;MD=-140.87,95%CI为-221.47^-60.27,P<0.001)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)水平(MD=-483.46,95%CI为-577.53^-389.39,P<0.001);且与对照组比较差异均有统计学意义。不良反应方面,阿帕替尼治疗组显著增加高血压发生率,RR=4.69,95%CI为3.29~6.67,P<0.001;其余不良反应与对照组差异无统计学意义,P>0.05。结论阿帕替尼治疗晚期实体恶性肿瘤比常规治疗更好地提高临床疗效,但也应注意高血压等不良反应。考虑到纳入研究总体质量中等偏上,期待更多高质量大样本的临床随机对照试验来支持本结论。

OBJECTIVE To evaluate the effectiveness and safety of Apatinib in the treatment of advanced solid ma- lignant tumor（such as advanced gastric cancer, non-small cell lung cancer, hepatocellular carcinoma,ovarian cancer,colon cancer, prostate cancer, etc. ） systematically,in order to provide evidence-based reference for clinical use. METHODS The pertinent randomized controlled trials（RCTs） about Apatinib trail group and control group in the treatment of advanced solid malignant tumor were retrieved from Cochrane Library, PubMed, VIP, CBM, CNKI and Wan fang Database. The quality of included studies were evaluated according to the risk of bias tables of Cochrane and modified Jadad scale. The re- lated data was extracted and Meta-analysis was performed by RevMan 5.3 statistical software. RESULTS A total of 36 RCTs were included, involving 2 469 patients. The results of Meta-analysis showed that objective response rate（ORR） [RR=1.45,95%CI：1.29,1.62,P〈0. 001] and disease control rate（DCR） [RR= 1.24,95%CI：1.12,1.37,P〈0. 001] were significantly improved ; the level of vascular endothelial growth factor （VEGF） [ MD = -140.87,95% CI ： -221.47, -60.27, P〈0. 001] and matrix metalloproteinase-9 （MMP-9） [MD=-483.46,95 % CI：- 577.53, -389.39, P〈0. 001 ] were markedly decreased and which was statistically different to control group （RR=4. 69,95% CI：3. 29,6. 67, P〈0. 001）. The adverse reactions of the incidence of hypertension were increased with statistically significant difference in Apatinib group （P〈0.05） ,other adverse reactions were nonsignificant difference （P〉0.05）. CONCLUSIONS Apatinib has good therapeutic efficacy in the treatment of advanced solid malignant tumor and effectively improves ORR and DCR. Meanwhile, the adverse reactions of hypertension were increased and should be concerned. On the whole, RCTs enrolled in this research were medium quality,the conclusion made in this paper needs to be further confirmed by high quality RCTs.