Dataset Information

Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis.

ABSTRACT:

Background and aim

A 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.

Methods

MEDLINE, 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).

Results

17 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; I(2) = 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; I(2) = 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.

Conclusions

Combination 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.

SUBMITTER: Liu L

PROVIDER: S-EPMC3961236 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis.

Liu Lei L Chen Hui H Chen Hui H Wang Mengmeng M Zhao Yan Y Cai Guohong G Qi Xingshun X Han Guohong G

PloS one 20140320 3

<h4>Background and aim</h4>A 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.<h4>Methods</h4>MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Library were searched from January 1990 to October 2013 and these ...[more]

PMID: 24651044

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Project description: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.

Project description:BACKGROUND:Transarterial chemoembolization (TACE) is the recommended treatment for hepatocellular carcinoma (HCC) patients at Barcelona Clinic Liver Cancer (BCLC) B-stage, whereas sorafenib is an orally administered small molecule target drug for BCLC C-stage. This updated systemic review and meta-analysis focuses on identifying the efficacy of the combination of TACE with sorafenib, which remains controversial despite years of exploration. METHODS:PubMed, EMBASE, Scopus and the Cochrane Library were systematically reviewed to search for studies published from January 1990 to May 2017. Studies focusing on the efficacy of combination therapy for unresectable HCC were eligible. The hazard ratio (HR) with 95% confidence intervals (95% CIs) for time to progression (TTP), overall survival (OS), disease control rate (DCR) and aetiology were collected. The data were then analysed through fixed/random effects meta-analysis models with STATA 13.0. The incidence and severity of treatment-related adverse events (AEs) were also evaluated. RESULTS:Twenty-seven studies were included. Thirteen non-comparative studies reported median OS (ranging from 18.5 to 20.4 months), median TTP (ranging from 7 to 13.9 months) and DCR (ranging from 18.4 to 95%). Fourteen comparative studies provided median OS (ranging from 7.0 to 29.7 months) and median TTP (ranging from 2.6 to 10.2 months). Five comparative studies provided DCR (ranging from 32 to 97.2%). Forest plots showed that combination therapy significantly improved TTP (HR?=?0.66, 95% CI 0.50-0.81, P?=?0.002) rather than OS (HR?=?0.63, 95% CI 0.55-0.71, P?=?0.058), compared to TACE alone. DCR increased significantly in the combination therapy group (OR?=?2.93, 95% CI 1.59-5.41, P?=?0.005). Additional forest plots were drawn and no significant differences were observed with regard to survival outcome among various aetiologies. Forest plots for separate analysis of regions showed the HR for TTP was 0.62 (95% CI 0.45-0.79, P?=?0.002) in the Asian countries group, and 0.82 (95% CI 0.59-1.05, P?=?0.504)) in western countries. The HR for OS was 0.61 (95% CI 0.48-0.75, P?=?0.050) in the Asian countries group and was 0.88 (95% CI 0.56-1.20, P?=?0.845) in western countries. These data may indicate positive TTP outcome in Asian patients but not in European patients while no positive findings regarding OS were observed in either region. The most common AEs included fatigue, hand-foot skin reaction, diarrhoea and hypertension. CONCLUSIONS:Combination therapy may benefit unresectable HCC patients in terms of prolonged TTP and DCR. More well-designed studies are needed to investigate its superiority for OS.

Dataset Information

Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis.

Background and aim

Methods

Results

Conclusions

Publications

Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis.

Similar Datasets

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