title: Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis.
abstract: OBJECTIVE
  The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib.
  
  
  METHODS
  Thirty-four patients with advanced HCC were treated with sorafenib regardless of liver function and prior anticancer therapy. Adverse events (AEs) were graded using Common Toxicity Criteria version 3.0, tumor response was assessed according to Response Evaluation Criteria in Solid Tumors.
  
  
  RESULTS
  Fifteen patients presented without LCI or with LCI Child- Pugh A, 15/4 patients had LCI Child-Pugh B/C. Barcelona Clinic Liver Cancer stage was B/C/D in 4/22/8 patients. During treatment period (median 2.2 mo), therapy was discontinued in 61.8% of patients due to tumor progression (32.3%), death (17.6%), AEs (8.8%), or noncompliance (2.9%). Most common grade 3/4 AEs included liver dysfunction (23.5%), diarrhea (14.7%), increased lipase (8.8%), fatigue (8.8%), and hand-foot skin reaction (5.9%). Worsening liver dysfunction/failure was more frequent (P=0.036) in patients with LCI Child-Pugh B/C compared with patients with maintained liver function (no LCI/LCI Child-Pugh A). Median overall survival was 7.2 months for patients with maintained liver function versus 3.3/3.4 months for patients with LCI Child-Pugh B/C.
  
  
  CONCLUSIONS
  These data do not support the use of sorafenib in patients with LCI Child-Pugh C, and patients with LCI Child-Pugh B should be treated with caution until larger trials provide more safety data and a clinically relevant survival benefit under sorafenib therapy.
authors.affiliation: I Department of Internal Medicine, Johannes Gutenberg-University Mainz, Germany. woerns@uni-mainz.de
authors.forename: Marcus Alexander
authors.initials: MA
authors.lastname: Wörns
authors.forename: Arndt
authors.initials: A
authors.lastname: Weinmann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Pfingst
authors.forename: Carla
authors.initials: C
authors.lastname: Schulte-Sasse
authors.forename: Claudia-Martina
authors.initials: CM
authors.lastname: Messow
authors.forename: Henning
authors.initials: H
authors.lastname: Schulze-Bergkamen
authors.forename: Andreas
authors.initials: A
authors.lastname: Teufel
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Kanzler
authors.forename: Christoph
authors.initials: C
authors.lastname: Düber
authors.forename: Gerd
authors.initials: G
authors.lastname: Otto
authors.forename: Peter Robert
authors.initials: PR
authors.lastname: Galle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000401:mortality / Q000473:pathology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D018579:Patient Selection; D010671:Phenylurea Compounds; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012720:Severity of Illness Index; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib