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

• Published in: PloS one Vol. 9; no. 3; p. e91124
• Main Authors: Liu, Lei, Chen, Hui, Wang, Mengmeng, Zhao, Yan, Cai, Guohong, Qi, Xingshun, Han, Guohong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20-03-2014; Public Library of Science (PLoS)
• Subjects: Alopecia; Analysis; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - surgery; Carcinoma, Hepatocellular - therapy; Cell survival; Chemoembolization, Therapeutic; Clinical trials; Combination therapy; Combined Modality Therapy; Comparative studies; Data bases; Diarrhea; Disease control; Disease Progression; Exanthema; Fatigue; Gastroenterology; Hematology; Hepatocellular carcinoma; Hepatotoxicity; Heterogeneity; Hospitals; Humans; Hypertension; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - surgery; Liver Neoplasms - therapy; Medical research; Medicine and Health Sciences; Meta-analysis; Metastasis; Nausea; Niacinamide - adverse effects; Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Patients; Phenylurea Compounds - adverse effects; Phenylurea Compounds - therapeutic use; Physical Sciences; Research and Analysis Methods; Response rates; Safety; Skin; Studies; Survival Analysis; Systematic review; Therapy; Time Factors; Toxicity; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091124

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.
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).
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.
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.