Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses

Jean Luc Raoul, Jordi Bruix, Tim F. Greten, Morris Sherman, Vincenzo Mazzaferro, Philip Hilgard, Hans Scherubl, Max E. Scheulen, Georgios Germanidis, Sophie Dominguez, Sergio Ricci, Andrea Nadel, Marius Moscovici, Dimitris Voliotis, Josep M. Llovet

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: 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.

Original languageEnglish
Pages (from-to)1080-1088
Number of pages9
JournalJournal of Hepatology
Volume56
Issue number5
DOIs
Publication statusPublished - May 2012

Keywords

  • Alanine aminotransferase
  • Alpha-fetoprotein
  • Aspartate aminotransferase
  • Bilirubin
  • Hepatic markers
  • Sorafenib

ASJC Scopus subject areas

  • Hepatology

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