Relationship between baseline hepatic status and outcome, and effect of sorafenib
on liver function: SHARP trial subanalyses.
Author(s): Raoul JL, Bruix J, Greten TF, Sherman M, Mazzaferro V, Hilgard P, Scherubl H,
Scheulen ME, Germanidis G, Dominguez S, Ricci S, Nadel A, Moscovici M, Voliotis
D, Llovet JM.
Affiliation(s): Institut Paoli-Calmettes, Marseille, France. raouljl@marseille.fnclcc.fr
Publication date & source: 2012, J Hepatol. , 56(5):1080-8
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.
|