title: Sorafenib for treatment of hepatocellular carcinoma: a systematic review.
abstract: BACKGROUND
  Sorafenib, a drug that inhibits Raf serine/threonine kinases mediating cell proliferation and receptor tyrosine kinases involved in angiogenesis, is approved for treatment of advanced hepatocellular carcinoma.
  
  
  OBJECTIVE
  To explore the efficacy and safety of sorafenib for treating advanced HCC, and to identify clinical factors that might affect that efficacy and safety.
  
  
  METHODS
  We conducted a systematic review using the PRISMA guidelines to identify prospective studies on sorafenib used alone or in combination with systemic and/or loco regional anti-tumor therapy for treating advanced HCC.
  
  
  RESULTS
  We identified 21 prospective trials of sorafenib treatment alone (7) or combined with other treatment (14). In randomized, placebo-controlled trials, sorafenib prolonged overall survival by 2.3-2.8 months, extended the time to tumor progression by 1.4-2.7 months, and increased disease control by 11-19 %. OS and DCRs were lowest for studies with the highest percentage of hepatitis B patients. Most studies reported major side effects (diarrhea, fatigue, and hand-foot syndrome) in <15 % of patients, with greater incidence in patients with advanced cirrhosis and those treated with sorafenib in combination with 5-FU drugs.
  
  
  CONCLUSIONS
  Treatment with sorafenib results in statistically significant, but clinically modest, improvements in OS, TTP, and DCR. For patients with hepatitis B, response seems to be poorer than for those with hepatitis C. The frequency of hand-foot syndrome seems to be higher when sorafenib is used in advanced cirrhosis and is combined with 5-FU drugs. It is not clear that sorafenib combined with other treatments is more effective than sorafenib alone.
authors.affiliation: Department of Medicine, VA North Texas Healthcare System, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. Bingru.Xie@va.gov
authors.forename: Bingru
authors.initials: B
authors.lastname: Xie
authors.forename: David H
authors.initials: DH
authors.lastname: Wang
authors.forename: Stuart Jon
authors.initials: SJ
authors.lastname: Spechler
mesh_terms: D024221:Antineoplastic Protocols; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D016461:Chemoembolization, Therapeutic / Q000379:methods; D060831:Hand-Foot Syndrome; D006525:Hepatitis, Viral, Human / Q000150:complications; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D000077157:Sorafenib; D016896:Treatment Outcome; D048490:raf Kinases / Q000378:metabolism
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D020794:Receptor Protein-Tyrosine Kinases; D048490:raf Kinases