中国临床药学杂志

目的系统评价阿帕替尼治疗中晚期原发性肝癌的疗效及安全性。方法计算机检索PubMed、Web of Science、Embase、Cochrane Library、SinoMed、CNKI、VIP、万方数据库,收集阿帕替尼治疗中晚期肝癌的随机对照研究,检索年限均为建库开始至2019年7月,由2位研究者独立进行文献筛选、资料提取和方法学质量评价后,采用Rev Man 5.2软件进行Meta分析。结果共纳入12项研究,合计823例患者。Meta分析显示,在疗效方面,试验组(阿帕替尼组)患者总有效率[RR=1.72, 95%CI(1.45, 2.04),P<0.01]、疾病控制率[RR=1.45, 95%CI(1.17,1.80),P<0.01]、半年生存期[RR=1.49, 95%CI(1.11,1.99),P<0.01]、1年生存期[RR=1.49, 95%CI(1.20,1.86),P<0.01]、 2年生存期[RR=1.69, 95%CI(1.20, 2.39),P<0.01]明显高于对照组(非阿帕替尼组);治疗后血清血管内皮生长因子(VEGF)[SMD=-3.37, 95%CI(-4.84,-1.90),P<0.01]和基质金属蛋白酶9(MMP-9)[SMD=-3.16, 95%CI(-5.30,-1.02),P<0.01]水平试验组明显低于对照组。在安全性方面,手足综合征[RR=16.73, 95%CI(6.27,44.6),P<0.01]、蛋白尿[RR=17.27,95%CI(5.52, 54.05),P<0.01]和瘙痒[RR=2.73, 95%CI(1.25,5.99),P=0.01]的发生率,试验组高于对照组且差异有统计学意义,但不影响治疗;高血压、骨髓抑制、腹痛腹泻、恶心呕吐和发热的发生率组间差异均无统计学意义。结论当前证据显示,阿帕替尼能提高中晚期肝癌的临床疗效,不良反应可以耐受,但该结论仍有待高质量、大样本的临床随机对照研究进一步验证。

AIM To systematically review the efficacy and safety of apatinib in treatment of advanced hepatocellular carcinoma(HCC), and provide evidence-based references for the clinical treatment. METHODS We searched PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, VIP and Wanfang databases to collect the randomized controlled trials(RCTs)published before July 2019 about apatinib in the treatment of advanced HCC. Two reviewers independently screened the studies, extracted data and evaluated the methodological quality and Meta analysis was performed by using Rev Man 5.2 statistics software. RESULTS A total of 12 RCTs were included, with 823 patients. Meta analysis showed that the total effectiveness[RR=1.72,95% CI(1.45,2.04),P<0.01] and the disease control rate[RR=1.45,95% CI(1.17,1.80),P<0.01] of the test group(apatinib group) were significantly higher than those of the control group(non-apatinib group); the half-year survival rate[RR=1.49, 95% CI(1.11,1.99), P<0.01], the one-year survival rate[RR=1.49, 95% CI(1.20,1.86), P<0.01] and the two-year survival rate [RR=1.69, 95% CI(1.20, 2.39), P<0.01] also showed statistical differences between 2 groups; the contents of vascular endothelial growth factor(VEGF) [SMD=-3.37, 95% CI(-4.84,-1.90), P<0.01], and matrix metalloprotein-9(MMP-9)[SMD=-3.16, 95% CI(-5.30,-1.02), P<0.01] in the test group were superior than those in the control group(P<0.05) after treatment, while there were no statistical differences before treatment. In terms of safety, the incidences of hand-foot syndrome[RR=16.73, 95% CI(6.27, 44.6), P<0.01], proteinuria[RR=17.27,95% CI(5.52,54.05),P<0.01] and pruritus[RR=2.73,95% CI(1.25,5.99),P=0.01] in the test group were higher than those in the control group, but almost had no impact on treatment. There were no statistical differences in incidences of hypertension, myelosuppression, abdominal pain and diarrhea, fever and nausea and vomiting(P>0.05). CONCLUSION Current evidence shows that apatinib can improve the clinical efficacy of the treatment of advanced hepatocellular carcinoma, and all the adverse reactions could be tolerated. Meanwhile, this conclusion needs to be further verified by high quality and large sample RCTs.