title: Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Health Services, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Cai
authors.affiliation: Department of Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xingshun
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Han
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D003131:Combined Modality Therapy; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib