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      Identifying the Best Anticancer Agent Combination in TACE for HCC Patients: A Network Meta-analysis

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          Abstract

          Objective: We conducted a network meta-analysis to comprehensively compare various anticancer agents used in transarterial chemoembolization (TACE) based on the Bayesian theorem.

          Methods: Globally recognized electronic databases, including PubMed, EMBASE, and Cochrane Central, were searched to retrieve relevant randomized controlled trials (RCTs) comparing anticancer agents in TACE for hepatocellular carcinoma (HCC) patients. The therapeutic response, adverse events and overall survival rate were selected as parametric data to evaluate the clinical efficacy. Quantitative network meta-analysis and pair-wise analysis were conducted to compare the relative parameters.

          Results: Of the 4242 retrieved articles, 17 RCTs containing 2330 patients fulfilled the inclusion criteria. The network meta-analysis exhibited that the application of anthracycline and mitomycin plus pyrimidine presented the best clinical values regarding all parametric data (probability P=0.45, 0.32 and 0.35 regarding comparison of response rate, adverse event and overall survival, respectively). Accordingly, further investigation on specific anticancer agents indicated that the combination of doxorubicin and mitomycin plus gemcitabine was the best agent combination in TACE (probability P=0.49, 0.37 and 0.77 regarding comparison of response rate, adverse event and overall survival, respectively). Moreover, an additional study indicated that the single use of an anticancer agent prior to embolism brought no benefit compared with bland embolism without any agent (Test Z=0.15, 0.84, 1.22 and P=0.88, 0.40, 0.22 regarding comparison of response rate, adverse event and overall survival, respectively). However, the combined use of anticancer agents in TACE showed significantly better clinical efficacy than single use (Test Z=4.40, 3.94, 0.24 and P<0.001, <0.001, =0.81 regarding comparison of response rate, adverse event and overall survival, respectively); thus, combination utilization was recommended.

          Conclusions: The combined use of anticancer agents in TACE was recommended. Application of anthracycline and mitomycin plus pyrimidine seemed to be the best choice for clinical consideration. Additionally, the combination of doxorubicin and mitomycin plus gemcitabine may be the best specific anticancer agent combination in TACE currently, although additional RCTs are expected to support our conclusion.

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          Most cited references34

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          Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver.

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            Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials.

            To review the available evidence of chemoembolization for unresectable hepatocellular carcinoma (HCC). Computerized bibliographic searches with MEDLINE and CANCERLIT databases from 1980 through 2000 were supplemented with manual searches, with the keywords "hepatocellular carcinoma," "liver cell carcinoma," "randomized controlled trial [RCT]," and "chemoembolization." Studies were included if patients with unresectable HCC were enrolled and if they were RCTs in which chemoembolization was compared with nonactive treatment (five RCTs) or if different transarterial modalities of therapy (13 RCTs) were compared. Data were extracted from each RCT according to the intention-to-treat method. Five of the RCTs with a nonactive treatment arm were combined by using the random-effects model, whereas all 18 RCTs were pooled from meta-regression analysis. Chemoembolization significantly reduced the overall 2-year mortality rate (odds ratio, 0.54; 95% CI: 0.33, 0.89; P =.015) compared with nonactive treatment. Analysis of comparative RCTs helped to predict that overall mortality was significantly lower in patients treated with transarterial embolization (TAE) than in those treated with transarterial chemotherapy (odds ratio, 0.72; 95% CI: 0.53, 0.98; P =.039) and that there is no evidence that transarterial chemoembolization is more effective than TAE (odds ratio, 1.007; 95% CI: 0.79, 1.27; P =.95), which suggests that the addition of an anticancer drug did not improve the therapeutic benefit. In patients with unresectable HCC, chemoembolization significantly improved the overall 2-year survival compared with nonactive treatment, but the magnitude of the benefit is relatively small.
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              Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization.

              Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh A or B) and disease aetiology. This suggests that not all patients with intermediate-stage HCC will derive similar benefit from TACE, and that some patients may benefit from other treatment options. Results of an extensive literature review into the treatment of unresectable HCC with TACE were combined with our own clinical experience to identify factors that may predict survival after TACE. We also report contraindications to TACE and propose a treatment algorithm for the repetition of TACE. In addition, we have constructed a number of expert opinions that may be used as a guide to help physicians make treatment decisions for their patients with intermediate-stage HCC. The data included in the literature review related almost exclusively to conventional TACE, rather than to TACE with drug-eluting beads. Therefore, the findings and conclusions of the literature review are only applicable to the treatment of HCC with conventional TACE. Treating physicians may want to consider other treatment options for patients with intermediate-stage HCC who are not suitable for or do not respond to TACE. By distinguishing those patients who represent good candidates for TACE from those where little or no benefit might be expected, it may be possible to make better use of current treatment options and improve outcomes for patients. Copyright © 2010. Published by Elsevier Ltd.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2018
                23 June 2018
                : 9
                : 15
                : 2640-2649
                Affiliations
                Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
                Author notes
                ✉ Corresponding authors: Zhen Li ( Doctor1989@ 123456whu.edu.cn ) and Zhisu Liu ( 2713845151@ 123456qq.com ), Department of General Surgery, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan 430071, China. Tel.: +86 027-67812588

                *These authors contributed equally to this work

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav09p2640
                10.7150/jca.25056
                6072806
                d520a1af-f1e5-4702-b0b6-e368cd94b39b
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 20 January 2018
                : 14 April 2018
                Categories
                Review

                Oncology & Radiotherapy
                anticancer agent,tace,network meta-analysis.
                Oncology & Radiotherapy
                anticancer agent, tace, network meta-analysis.

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