TY - JOUR
T1 - A Phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis
AU - Santoro, A.
AU - Simonelli, M.
AU - Rodriguez-Lope, C.
AU - Zucali, P.
AU - Camacho, L. H.
AU - Granito, A.
AU - Senzer, N.
AU - Rimassa, L.
AU - Abbadessa, G.
AU - Schwartz, B.
AU - Lamar, M.
AU - Savage, R. E.
AU - Bruix, J.
PY - 2013/1/15
Y1 - 2013/1/15
N2 - Background:The mesenchymal-epithelial transition factor (MET) receptor is dysregulated in hepatocellular carcinoma (HCC), and tivantinib (ARQ 197) is an oral, selective, MET inhibitor.Methods:This Phase-1b study assessed tivantinib safety as primary objective in patients with previously treated HCC and Child-Pugh A or B liver cirrhosis. Patients received oral tivantinib 360 mg twice daily until disease progression or unacceptable toxicity.Results:Among 21 HCC patients, common drug-related adverse events (AEs) were neutropaenia, anaemia, asthenia, leucopaenia, anorexia, diarrhoea, and fatigue. No drug-related worsening of liver function or performance status occurred, but one Child-Pugh B patient experienced drug-related bilirubin increase. Four patients had drug-related serious AEs, including one neutropaenia-related death. Haematologic toxicities were more frequent than in previous tivantinib studies but were manageable with prompt therapy. Best response was stable disease (median, 5.3 months) in 9 of 16 evaluable patients (56%). Median time to progression was 3.3 months.Conclusion:Tivantinib demonstrated a manageable safety profile and preliminary antitumour activity in patients with HCC and Child-Pugh A or B cirrhosis.
AB - Background:The mesenchymal-epithelial transition factor (MET) receptor is dysregulated in hepatocellular carcinoma (HCC), and tivantinib (ARQ 197) is an oral, selective, MET inhibitor.Methods:This Phase-1b study assessed tivantinib safety as primary objective in patients with previously treated HCC and Child-Pugh A or B liver cirrhosis. Patients received oral tivantinib 360 mg twice daily until disease progression or unacceptable toxicity.Results:Among 21 HCC patients, common drug-related adverse events (AEs) were neutropaenia, anaemia, asthenia, leucopaenia, anorexia, diarrhoea, and fatigue. No drug-related worsening of liver function or performance status occurred, but one Child-Pugh B patient experienced drug-related bilirubin increase. Four patients had drug-related serious AEs, including one neutropaenia-related death. Haematologic toxicities were more frequent than in previous tivantinib studies but were manageable with prompt therapy. Best response was stable disease (median, 5.3 months) in 9 of 16 evaluable patients (56%). Median time to progression was 3.3 months.Conclusion:Tivantinib demonstrated a manageable safety profile and preliminary antitumour activity in patients with HCC and Child-Pugh A or B cirrhosis.
KW - Hepatocellular carcinoma
KW - liver cirrhosis
KW - liver function
KW - MET inhibitor
KW - tivantinib
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U2 - 10.1038/bjc.2012.556
DO - 10.1038/bjc.2012.556
M3 - Article
C2 - 23287988
AN - SCOPUS:84872600260
SN - 0007-0920
VL - 108
SP - 21
EP - 24
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 1
ER -