对于晚期肝细胞癌患者，与阿帕替尼联合用于经动脉化疗栓塞治疗的最合适药物是什么？一项系统评价和网状Meta分析。
What Is the Most Suitable Agent Combined With Apatinib for Transarterial Chemoembolization Treatment in Advanced Hepatocellular Carcinoma Patients? A Systematic Review and Network Meta-analysis.
作者信息
Hui Fuhai, Xu Chang, Xu Xiangbo, Chen Jiangxia, Geng Hefeng, Yang Chao, Zhang Yingshi
机构信息
Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Department of Ethnic Culture and Vocational Education, Liaoning National Normal College, Shenyang, China.
出版信息
Front Oncol. 2022 May 25;12:887332. doi: 10.3389/fonc.2022.887332. eCollection 2022.
PURPOSE
Combined therapy with transarterial chemoembolization (TACE) and apatinib is superior in therapeutic effect compared with TACE alone in patients with hepatocellular carcinoma (HCC). To determine the most suitable agent combined with apatinib for TACE treatment, we did a systematic review and network meta-analysis.
METHODS
Four electronic databases were searched from inception until November 2021. Randomized controlled trials (RCTs) and retrospective studies that combined therapy of TACE and apatinib (TACE+A) compared with TACE alone were included. We performed random-effect pairwise and network meta-analyses to summarize the outcomes about efficacy and safety.
RESULTS
Forty-five original studies including 3,876 patients were included. In terms of efficacy, we evaluated treatment response, 6 months overall survival (OS), 1 year OS, 6 months progression-free survival (PFS), 1 year PFS, alphafetoprotein (AFP), matrix metalloproteinase 9 (MMP9), and vascular endothelial growth factor (VEGF). Significant differences always appear in TACE agent subgroups of adriamycin, platinum, and fluorouracil from both pairwise and network meta-analysis, while significant differences could also be found in apatinib dosage of 500 and >500 mg/day subgroups and in both RCT and retrospective study subgroups. From second time network analysis, compared with TACE alone, subgroups with TACE agents of oxaliplatin, cisplatin, pirarubicin, epirubicin, and 5-fluorouracil ranked front. In addition, the safety of adriamycin, platinum, and fluorouracil subgroups is acceptable.
CONCLUSIONS
In conclusion, the most suitable agents in TACE combined with apatinib were adriamycin+platinum ± fluorouracil combination therapy.
SYSTEMATIC REVIEW REGISTRATION
The study was registered with https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311650, PROSPERO, CRD4202022311650.
目的
对于肝细胞癌（HCC）患者，经动脉化疗栓塞术（TACE）联合阿帕替尼的联合治疗在疗效上优于单纯TACE治疗。为确定与阿帕替尼联合用于TACE治疗的最合适药物，我们进行了一项系统评价和网状Meta分析。
方法
检索了4个电子数据库，检索时间从建库至2021年11月。纳入了比较TACE联合阿帕替尼（TACE+A）与单纯TACE联合治疗的随机对照试验（RCT）和回顾性研究。我们进行了随机效应成对和网状Meta分析，以总结疗效和安全性方面的结果。
结果
纳入了45项原始研究，共3876例患者。在疗效方面，我们评估了治疗反应、6个月总生存期（OS）、1年OS、6个月无进展生存期（PFS）、1年PFS、甲胎蛋白（AFP）、基质金属蛋白酶9（MMP9）和血管内皮生长因子（VEGF）。成对和网状Meta分析在阿霉素、铂和氟尿嘧啶的TACE药物亚组中均始终出现显著差异，而在阿帕替尼剂量为500和>500mg/天的亚组以及RCT和回顾性研究亚组中也能发现显著差异。从第二次网状分析来看，与单纯TACE相比，奥沙利铂、顺铂、吡柔比星、表柔比星和5-氟尿嘧啶的TACE药物亚组排名靠前。此外，阿霉素、铂和氟尿嘧啶亚组的安全性是可接受的。
结论
总之，TACE联合阿帕替尼治疗中最合适的药物是阿霉素+铂±氟尿嘧啶联合治疗。
系统评价注册
该研究已在https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311650（PROSPERO，CRD4202022311650）注册。
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