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Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma.
- Source :
-
Cancer [Cancer] 2013 Jan 15; Vol. 119 (2), pp. 380-7. Date of Electronic Publication: 2012 Jul 25. - Publication Year :
- 2013
-
Abstract
- Background: The efficacy and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases, were assessed in this phase 2, single-arm, open-label, multicenter trial.<br />Methods: Eligible patients had unresectable or metastatic hepatocellular carcinoma and had received ≤ 1 prior systemic therapy. Patients received oral linifanib at a fasting dose of 0.25 mg/kg,. The primary endpoint was the progression-free rate at 16 weeks. Tumor response was assessed every 8 weeks. Secondary endpoints included the time to disease progression, overall survival, and objective response rate. Safety was also assessed.<br />Results: Of the 44 patients enrolled, the majority were Asian (89%), had received no prior systemic therapy (82%), had Child-Pugh class A hepatic function (86%), and had hepatitis B virus infection (61%). The estimated progression-free rate at 16 weeks was 31.8% (34.2% for patients with Child-Pugh class A hepatic function), the estimated objective response rate was 9.1% (10.5% for patients with Child-Pugh class A hepatic function), the median time to disease progression was 3.7 months (3.7 months for patients with Child-Pugh class A hepatic function), and the median overall survival was 9.7 months (10.4 months for patients with Child-Pugh class A hepatic function). The most common linifanib-related adverse events were diarrhea (55%) and fatigue (52%). The most common linifanib-related grade 3/4 adverse events were hypertension (25%) and fatigue (14%). Serum levels of biomarkers cancer antigen (CA) 125, cytokeratin fragment (CYFRA)21.1, and protein induced by vitamin K absence or antagonist II (PIVKA) demonstrated potential as prognostic indicators of patient response or outcome.<br />Conclusions: Single-agent linifanib was found to be clinically active in patients with advanced hepatocellular carcinoma, with an acceptable safety profile.<br /> (Copyright © 2012 American Cancer Society.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Antineoplastic Agents adverse effects
Antineoplastic Agents pharmacology
Biomarkers, Tumor blood
Carcinoma, Hepatocellular blood
Carcinoma, Hepatocellular mortality
Carcinoma, Hepatocellular secondary
Diarrhea chemically induced
Disease-Free Survival
Fatigue chemically induced
Female
Humans
Indazoles adverse effects
Indazoles pharmacology
Kaplan-Meier Estimate
Liver Neoplasms blood
Liver Neoplasms mortality
Lung Neoplasms blood
Lung Neoplasms mortality
Lung Neoplasms secondary
Lymphatic Metastasis
Male
Middle Aged
Phenylurea Compounds adverse effects
Phenylurea Compounds pharmacology
Treatment Outcome
Tumor Burden drug effects
Young Adult
Antineoplastic Agents therapeutic use
Carcinoma, Hepatocellular drug therapy
Indazoles therapeutic use
Liver Neoplasms drug therapy
Liver Neoplasms pathology
Lung Neoplasms drug therapy
Phenylurea Compounds therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0142
- Volume :
- 119
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 22833179
- Full Text :
- https://doi.org/10.1002/cncr.27758