title: Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses.
abstract: OBJECTIVE
  Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and, by measuring organ damage and tumor stage, can influence treatment. Moreover, elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma. We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, and bilirubin; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment.
  
  
  METHODS
  Patients (n=602) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase (not significantly elevated, mildly elevated, or moderately elevated), alpha-fetoprotein (normal or elevated), and bilirubin (normal or elevated). Bilirubin was measured at baseline and on day 1 of each cycle.
  
  
  RESULTS
  Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin had shorter overall survival (OS) than those with normal baseline concentrations, irrespective of treatment group. No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin. Median changes from baseline in bilirubin concentration at the last cycle of treatment were +0.17 and +0.19 mg/dl in the sorafenib and placebo groups, respectively.
  
  
  CONCLUSIONS
  These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma, irrespective of baseline alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy.
authors.affiliation: Institut Paoli-Calmettes, Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U991, Rennes, France. Electronic address: raouljl@marseille.fnclcc.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Raoul
authors.affiliation: Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, CIBERehd, Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Hospital Clínic Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
authors.affiliation: Medizinische Hochschule Hannover, Abteilung fur Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Germany.
authors.forename: Tim F
authors.initials: TF
authors.lastname: Greten
authors.affiliation: Toronto General Hospital, Toronto, ON, Canada.
authors.forename: Morris
authors.initials: M
authors.lastname: Sherman
authors.affiliation: National Cancer Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mazzaferro
authors.affiliation: University Hospital of Essen, Essen, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Hilgard
authors.affiliation: Medizinische Klinik "Charite", Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Scherubl
authors.affiliation: Innere Klinik (Tumorforschung), West German Cancer Center, Universitätsklinikum Essen, Essen, Germany.
authors.forename: Max E
authors.initials: ME
authors.lastname: Scheulen
authors.affiliation: AHEPA University Hospital, First Department of Medicine, Thessaloniki, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Germanidis
authors.affiliation: Centre Oscar Lambret, Departement de Cancerologie Digestive et Urologique, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dominguez
authors.affiliation: St. Chiara University Hospital, Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ricci
authors.affiliation: Bayer HealthCare Pharmaceuticals, Montville, NJ, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nadel
authors.affiliation: Bayer Schering Pharma, Milan, Italy.
authors.forename: Marius
authors.initials: M
authors.lastname: Moscovici
authors.affiliation: Bayer Schering Pharma, Milan, Italy.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Voliotis
authors.affiliation: Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, CIBERehd, Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Hospital Clínic Barcelona, Barcelona, Spain; Mount Sinai Liver Cancer Program, Mount Sinai School of Medicine, New York, NY, USA; Institució Catalana de Recerca I Estudis Avançats, Catalonia, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llovet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000401:mortality; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000077157:Sorafenib; D015996:Survival Rate; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D015415:Biomarkers; D010671:Phenylurea Compounds; D011725:Pyridines; D000509:alpha-Fetoproteins; D009536:Niacinamide; D000077157:Sorafenib; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin