title: Sorafenib improves the survival of patients with advanced hepatocellular carcinoma: a meta-analysis of randomized trials.
abstract: There is no effective systemic therapy for patients with advanced hepatocellular carcinoma (HCC) except liver transplantation. Sorafenib, a multikinase inhibitor, has been shown to significantly increase overall survival (OS) in a randomized, placebo-controlled, phase III trial of patients with HCC (SHARP). The aim of this study was to evaluate the effectiveness of sorafenib for advanced HCC by carrying out a meta-analysis of randomized controlled trials that compared sorafenib-based therapy with other agent-based therapy. Randomized controlled trials comparing sorafenib or combined chemotherapy with placebo or combined chemotherapy in advanced HCC between 2000 and 2008 were identified and the data were extracted from reports. Outcomes analyzed were objective response rate, time to progression (TTP), OS, and toxicity. The summary hazard ratios (HRs), odds ratios, and their 95% confidence intervals (CIs) for mortality, objective response rate, and toxicity were estimated. All statistical tests were two-sided. Three trials including 924 patients were identified. Sorafenib-based chemotherapy was also associated with a 79% prolongation of TPP (HR = 0.58, 95% CI = 0.49-0.69, P<0.001), and a 37.3% increase in OS (HR = 0.66, 95% CI = 0.55-0.78, P<0.001). Despite significant increases in the frequencies of hand-foot syndrome and diarrhea in patients receiving sorafenib-containing chemotherapy, no significant difference in other toxic events was observed. This meta-analysis suggests that sorafenib-based chemotherapy is superior to placebo-based chemotherapy in terms of TPP and OS without increase in severe toxic effects.
authors.affiliation: Department of Oncology, PLA General Hospital of Chengdu Military Region, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Ding
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Su
authors.forename: Huanyi
authors.initials: H
authors.lastname: Liu
authors.forename: Daoyuan
authors.initials: D
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D003967:Diarrhea / Q000139:chemically induced; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000077157:Sorafenib; D013577:Syndrome; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib