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

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.