替吉奥联合经肝动脉化疗栓塞治疗原发性肝癌疗效及安全性的Meta分析
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摘要
目的评价替吉奥联合经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)治疗原发性肝癌的疗效及安全性。方法使用计算机检索从建库至2018年2月公开发表在Pub Med、Embase、Cochrane和中国期刊全文数据库等多个数据库中替吉奥联合TACE与单独TACE治疗原发性肝癌的疗效相比较的临床研究文献。并使用Rev Man 5.3对所纳入的研究进行Meta分析,使用Begg法和Egger法分析发表偏倚。结果最终纳入9篇研究文献,共569例原发性肝癌患者。其中包括随机对照研究8篇和队列研究1篇。替吉奥联合TACE治疗原发性肝癌的客观有效率及疾病控制率分别为69.8%和89.9%,均优于单独使用TACE的42.9%和65.6%(P均<0.05);替吉奥联合TACE治疗原发性肝癌的1年、2年及3年总体生存率分别为80.00%、49.74%和37.64%,明显高于单独使用TACE治疗的53.33%、24.10%和14.12%(P均<0.05)。不良反应以骨髓抑制、恶心、呕吐、腹痛和发热多见,予以对症处理后好转,无其他严重不良反应。结论替吉奥联合TACE治疗原发性肝癌优于TACE治疗,可提高临床疗效,改善患者总体生存率且不良反应可耐受。
Objective To assess the efficacy and safety of transcatheter arterial chemoembolization(TACE) combined with S-1 in the treatment of primary hepatic carcinoma(PHC). Methods The published clinical studies regarding the comparison of TACE combined with S-1 and TACE alone in treatment of PHC were collected through a computer-based retrieval from the launching to February 2018, by using Pub Med, Embase, Cochrane and China National Knowledge Internet Full-text Databases. Rev Man 5.3 software was used for Meta analysis. Publication bias was assessed with Begg and Egger. Results Nine studies involving in 569 PHC cases were enrolled in this study, including 8 randomized controlled trials and 1 cohort study. The objective response rate and disease control rate of TACE combined with S-1 in treatment of PHC were 69.8% and 89.9% respectively, which were higher than those of TACE alone, 42.9% and 65.6%(P <0.05). The one-year, two-year and three-year overall survival rates of TACE combined with S-1 in treatment of PHC were 80.00%, 49.74% and 37.64%, which were obviously higher than those of TACE alone(53.33%, 24.10% and 14.12%, P <0.05). Adverse events were mainly bone marrow suppression, nausea, vomiting, abdominal pain and fever, which were improved after symptomatic treatment. No other severe adverse events were observed. Conclusions S-1 combined with TACE in the treatment of PHC is superior to TACE alone. It can improve clinical effect and overall survival rate with tolerable adverse reactions.
Objective To assess the efficacy and safety of transcatheter arterial chemoembolization(TACE) combined with S-1 in the treatment of primary hepatic carcinoma(PHC). Methods The published clinical studies regarding the comparison of TACE combined with S-1 and TACE alone in treatment of PHC were collected through a computer-based retrieval from the launching to February 2018, by using Pub Med, Embase, Cochrane and China National Knowledge Internet Full-text Databases. Rev Man 5.3 software was used for Meta analysis. Publication bias was assessed with Begg and Egger. Results Nine studies involving in 569 PHC cases were enrolled in this study, including 8 randomized controlled trials and 1 cohort study. The objective response rate and disease control rate of TACE combined with S-1 in treatment of PHC were 69.8% and 89.9% respectively, which were higher than those of TACE alone, 42.9% and 65.6%(P <0.05). The one-year, two-year and three-year overall survival rates of TACE combined with S-1 in treatment of PHC were 80.00%, 49.74% and 37.64%, which were obviously higher than those of TACE alone(53.33%, 24.10% and 14.12%, P <0.05). Adverse events were mainly bone marrow suppression, nausea, vomiting, abdominal pain and fever, which were improved after symptomatic treatment. No other severe adverse events were observed. Conclusions S-1 combined with TACE in the treatment of PHC is superior to TACE alone. It can improve clinical effect and overall survival rate with tolerable adverse reactions.
引文
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[19]Lencioni R,Llovet JM,Han G,et al.Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate-stage HCC:phase II,randomized,double-blind SPACE trial[J].J Hepatol,2016,64(5):1090-1098.
[20]Chao Y,Chung YH,Han G,et al.The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma:final results of the START trial[J].Int J Cancer,2015,136(6):1458-1467.
[21]Chen FG,Wang JJ,Xue Q.Inhibition of angiogenesis of LCI-D20 hepatocellular carcinoma by metronomic chemotherapy of S-1[J].Zhonghua Gan Zang Bing Za Zhi,2009,17(9):665-668.
[22]Furuse J,Okusaka T,Kaneko S,et al.Phase I/II study of the pharmacokinetics,safety and efficacy of S-1 in patients with advanced hepatocellular carcinoma[J].Cancer Sci,2010,101(12):2606-2611.
[23]Hoff PM.The tegafur-based dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines,UFT/leucovorin(ORZEL)and S-1:a review of their clinical development and therapeutic potential[J].Invest New Drugs,2000,18(4):331-342.
[2]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[3]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[4]Schlachterman A,Jr WWC,Hilgenfeldt E,et al.Current and future treatments for hepatocellular carcinoma.[J].World J Gast,2015,21(28):8478-8491.
[5]张宁,卢姗姗,Rifaat,等.肝内胆管细胞癌诊断及治疗的现状与挑战[J].传染病信息,2018,31(1):24-30.
[6]European Association for the study of the Liver,European organisation for research and treatment of cancer.EASL-EORTC clinical practice guidelines:management of hepatocellular carcinoma[J].J Hepatol,2012,56(4):908-943.
[7]杨家进,吴建兵.原发性肝癌综合介入治疗进展[J].实用肝脏病杂志,2015,18(2):118-119.
[8]Liu J,Yi J.Relationship between the changes of VEGF level and dendritic cells in peripheral blood of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization[J].J Huazhong Univ Sci Technolog Med Sci,2007,27(1):58-60.
[9]Huang WK,Yang SF,You LN,et al.Transcatheter arterial chemoembolisation(TACE)plus S-1 for the treatment of BCLC stage B hepatocellular carcinoma refractory to TACE[J].Contemp Oncol,2016,20(6):468-474.
[10]张呈,陈昌南,林云笑,等.替吉奥联合经肝动脉化疗栓塞治疗中晚期肝细胞癌的疗效观察[J].临床肝胆病杂志,2014,30(1):55-57.
[11]桑泽杰,王华明,纪卫政,等.巴塞罗那肝癌分期B期、C期原发性肝癌患者肝动脉灌注化疗栓塞术后长期口服低剂量替吉奥的疗效观察[J].中国全科医学,2015,18(27):3324-3327.
[12]余小红,娄继滨,晏继喜,等.替吉奥持续低剂量口服联合小剂量TACE治疗原发性肝癌疗效观察[J].重庆医学,2015,44(24):3367-3369.
[13]祝金冉,杨静.经肝动脉化疗栓塞联合替吉奥治疗中晚期肝细胞癌的疗效及安全性评价[J].中国实用医药,2016,11(28):180-181.
[14]覃文办,李永标,唐超莉,等.TACE联合替吉奥治疗原发性肝癌的近期疗效、毒副作用及生存情况观察[J].中国医药导报,2017,14(23):71-74,79.
[15]王海存,王萌萌,曹旸.肝动脉化疗栓塞术后应用奥沙利铂联合替吉奥治疗晚期原发性肝癌的临床观察[J].中国药房,2017,28(11):1555-1558.
[16]黄伍奎,帕哈尔丁·白克热,刘墨,等.替吉奥节拍性化疗联合TACE治疗晚期HCC的安全性分析[J].中国医学创新,2017,14(4):75-78.
[17]蒋长晨,朱锡旭,丁涤非,等.替吉奥联合TACE治疗BCLCB期原发性肝癌疗效分析[J].现代肿瘤医学,2017,25(22):3660-3664.
[18]Lencioni R,Llovet JM,Han G,et al.Sorafenib or placebo in combination with transarterial chemoembolization(TACE)with doxorubicin-eluting beads(DEBDOX)for intermediate-stage hepatocellular carcinoma(HCC):phase II,randomized,double-blind SPACE trial[J].Asco Meeting Abstracts,2012,30(4 suppl).
[19]Lencioni R,Llovet JM,Han G,et al.Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate-stage HCC:phase II,randomized,double-blind SPACE trial[J].J Hepatol,2016,64(5):1090-1098.
[20]Chao Y,Chung YH,Han G,et al.The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma:final results of the START trial[J].Int J Cancer,2015,136(6):1458-1467.
[21]Chen FG,Wang JJ,Xue Q.Inhibition of angiogenesis of LCI-D20 hepatocellular carcinoma by metronomic chemotherapy of S-1[J].Zhonghua Gan Zang Bing Za Zhi,2009,17(9):665-668.
[22]Furuse J,Okusaka T,Kaneko S,et al.Phase I/II study of the pharmacokinetics,safety and efficacy of S-1 in patients with advanced hepatocellular carcinoma[J].Cancer Sci,2010,101(12):2606-2611.
[23]Hoff PM.The tegafur-based dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines,UFT/leucovorin(ORZEL)and S-1:a review of their clinical development and therapeutic potential[J].Invest New Drugs,2000,18(4):331-342.