雷替曲塞治疗中晚期原发性肝癌的疗效与安全性的Meta分析

Clinical Efficacy and Safety of Raltitrexed in the Treatment of Advanced Primary Hepatocellular Carcinom: a Meta-analysis

目的:采用Meta分析方法评价雷替曲塞治疗中晚期原发性肝癌的疗效及安全性。方法:计算机检索Pub Med、Web of Science、Embase、The Cochrane Library、Sino Med、CNKI、VIP、Wan Fang Data数据库,收集雷替曲塞治疗中晚期原发性肝癌的随机对照试验(RCTs),检索年限均为建库开始至2017年12月,由两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8项研究,合计821例患者。Meta分析显示,在疗效方面,试验组(雷替曲塞治疗)患者总有效率[OR=2.09,95%CI(1.48,2.93),P<0.001]、疾病控制率[OR=2.63,95%CI(1.90,3.64),P<0.001]、1年生存率[OR=2.12,95%CI(1.34,3.34),P=0.001]、2年生存率[OR=2.93,95%CI(1.76,4.88),P<0.001]、甲胎蛋白下降率[OR=3.36,95%CI(1.98,5.69),P<0.001]、转氨酶下降率[OR=2.99,95%CI(1.65,5.43),P<0.001]、胆红素下降率[OR=3.07,95%CI(1.70,5.55),P<0.001],均显著高于对照组(非雷替曲塞治疗),且差异有统计学意义。在安全性方面,试验组不良反应的发生率均低于对照组,其中胃肠道反应的有统计学意义[OR=0.62,95%CI(0.41,0.93),P<0.05]。结论:当前证据显示,雷替曲塞能提高中晚期原发性肝癌的临床疗效,同时减少不良反应发生,该结论有待高质量、大样本的RCTs进一步验证。

Objective： To systematically review the efficacy and safety of raltitrexed in the treatment of advanced primary hepatocellular carcinoma（ HCC） to provide evidence-based reference for the clinical treatment. Methods： Pub Med,Web of Science,Embase,Cochrane Library,Sino Med,CNKI,VIP and Wan Fang Data were searched to collect the randomized controlled trials（ RCTs） on raltitrexed in the treatment of advanced primary hepatocellular carcinoma published till December 2017. Two reviewers independently screened the studies,extracted the data and evaluated the methodological quality,and then meta-analysis was performed by using Rev Man 5. 0 statistics software. Results： A total of 8 RCTs were included with 821 patients. Meta-analysis showed that the total effective rate [OR = 2. 09,95% CI（ 1. 48,2. 93）,P 0. 001]and the disease control rate [OR = 2. 63,95% CI（ 1. 90,3. 64）,P 0. 001]of the test group（ raltitrexed group） were significantly higher than those of the control group; the one-year survival rate [OR = 2. 12,95% CI（ 1. 34,3. 34）,P 0. 001]and the two-year survival rate [OR = 2. 93,95% CI（ 1. 76,4. 88）,P 0. 001]also showed statistical differences between the groups; the decline rates of AFP [OR = 3. 36,95% CI（ 1. 98,5. 69）,P 0. 001],transaminase [OR= 2. 99,95% CI（ 1. 65,5. 43）,P 0. 001]and bilirubin [OR = 3. 07,95% CI（ 1. 70,5. 55）,P 0. 001]were significantly higher than those in the control group. In terms of safety,the gastrointestinal toxicity of the test group [OR = 0. 62,95% CI（ 0. 41,0. 93）,P〈0. 05] was lower than that of the control group. The incidence differences of leukocyte decline,fever,myelosuppression,neurotoxicity and liver dysfunction were not statistically significant（ P〈0. 05）. Conclusion： Current evidence shows that raltitrexed can improve the clinical efficacy and reduce the side effects in the treatment of advanced hepatocellular carcinoma,which should be further verified by RCTs with higher quality and larger sample.