Combination Therapy of Sorafenib and TACE for Unresectable HCC: A Systematic Review and Meta-Analysis

Abstract

Background and AimA large number of studies have tried to combine sorafenib with TACE for patients with unresectable hepatocellular carcinoma (HCC) and the results were controversial. We conducted this systematic review and meta-analysis to evaluate the safety and efficacy of combination therapy of sorafenib and TACE in the management of unresectable HCC.MethodsMEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Library were searched from January 1990 to October 2013 and these databases were searched for appropriate studies combining TACE and sorafenib in treatment of HCC. Two authors independently reviewed the databases and extracted the data and disagreements were resolved by discussion. Effective value and safety were analyzed. Effective value included disease control rate (DCR), time to progression (TTP) and overall survival (OS).Results17 studies were included in the study. In the 10 noncomparative studies, DCR ranged from 18.4 to 91.2%. Median TTP ranged from 7.1 to 9.0 months, and median OS ranged from 12 to 27 months. In the 7 comparative studies, the hazard ratio (HR) for TTP was found to be 0.76 (95% CI 0.66–0.89; P<0.001) with low heterogeneity among studies (P = 0.243; I2 = 25.5%). However, the HR for OS was found to be 0.81 (95% CI 0.65–1.01; P = 0.061) with low heterogeneity among studies (P = 0.259; I2 = 25.4%). The common toxicities included fatigue, diarrhea, nausea, hand foot skin reaction (HFSR), hematological events, hepatotoxicity, alopecia, hepatotoxicity, hypertension and rash/desquamation. AEs are generally manageable with dose reductions.ConclusionsCombination therapy may bring benefits for unresectable HCC patients in terms of TTP but not OS. Further well-designed randomized controlled studies are needed to confirm the efficacy of combination therapy.

Hepatocellular carcinoma: A comprehensive review

“…In the recent sorafenib as Adjuvant Treatment in the Prevention of Recurrence of Hepatocellular Carcinoma trial, effectiveness and safety with supplementary sorafenib was tested. Eligibility criteria included individuals that underwent local ablative therapy or resection surgically, with the intention of a cure but developed a significant risk of recurrence [99] . The main criteria for inclusion included: CP score between five and seven, ECOG PS 0, with the lack of any redevelopment measured by CT or MRI.…”

Hepatic Resection after Initial Transarterial Chemoembolization Versus Transarterial Chemoembolization Alone for the Treatment of Hepatocellular Carcinoma: A Meta-analysis of Observational Studies

“…Based on the ART scoring system, we could identify the patients who would have a dismal prognosis if retreated with a second TACE session. Second, the evidence from several meta-analyses suggested the advantages of TACE in combination with sorafenib over TACE alone in terms of overall survival (OS), time to progression, objective response rate, and progression free survival (Fu et al, 2014;Liu et al, 2014;Zhang et al, 2014). Thus, a combination of sorafenib should be attempted in patients at a relatively late stage of HCC.…”

Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model

“…Therefore, combining TACE with systemic sorafenib treatment may be an attractive concept (13,14). Clinical data still remain inconclusive (15)(16)(17). Although the toxicity of such a combined regimen (TACE plus sorafenib) does not seem to exceed the toxicity conferred by each of the two modalities alone, the overall toxicity of systemic sorafenib remains high.…”