title: Sorafenib in advanced hepatocellular carcinoma.
abstract: BACKGROUND
  No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma.
  
  
  METHODS
  In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety.
  
  
  RESULTS
  At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group.
  
  
  CONCLUSIONS
  In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.)
authors.affiliation: Barcelona Clinic Liver Cancer Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigaciones en Red de Enfermedades Hepáticas y Digestivas Hospital Clínic Barcelona, Barcelona. jmllovet@clinic.ub.es
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llovet
authors.forename: Sergio
authors.initials: S
authors.lastname: Ricci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mazzaferro
authors.forename: Philip
authors.initials: P
authors.lastname: Hilgard
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Blanc
authors.forename: Andre Cosme
authors.initials: AC
authors.lastname: de Oliveira
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Raoul
authors.forename: Alejandro
authors.initials: A
authors.lastname: Forner
authors.forename: Myron
authors.initials: M
authors.lastname: Schwartz
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.forename: Tim F
authors.initials: TF
authors.lastname: Greten
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.forename: Ivan
authors.initials: I
authors.lastname: Borbath
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Tom
authors.initials: T
authors.lastname: Giannaris
authors.forename: Minghua
authors.initials: M
authors.lastname: Shan
authors.forename: Marius
authors.initials: M
authors.lastname: Moscovici
authors.forename: Dimitris
authors.initials: D
authors.lastname: Voliotis
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
mesh_terms: D000368:Aged; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016019:Survival Analysis; D048490:raf Kinases / Q000037:antagonists & inhibitors*
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048490:raf Kinases