Tivozanib (
AV-951;
KRN-951), being developed by AVEO
Pharmaceuticals Inc and Kyowa Hakko Kirin Co Ltd, is an orally active,
ATP-competitive, small-molecule,
quinoline-
urea derivative that inhibits VEGFR
tyrosine kinase for the potential treatment of
cancer. In particular,
tivozanib is able to markedly inhibit the
ligand-induced phosphorylation of
VEGFR-1,
VEGFR-2 and
VEGFR-3 at picomolar concentrations. In preclinical studies,
tivozanib produced a significant inhibition of
tumor growth and angiogenesis in several different xenograft
tumor models in athymic rats. In a phase I clinical trial,
tivozanib was safe and tolerable when administered at oral doses up to 1.5 mg on a schedule of 4 weeks on, 2 weeks off treatment. Results from a phase II clinical trial in patients with advanced
renal cell carcinoma reported an overall response rate of 25.4% and a median progression-free survival of 11.8 months in patients treated with
tivozanib as a single agent.
Hypertension and
dysphonia were the most frequent adverse events. At the time of publication, a phase III clinical trial was recruiting patients with advanced
renal cancer to assess
tivozanib in comparison with
sorafenib. Clinical trials are currently ongoing to evaluate the safety and antitumor activity of
tivozanib in breast, lung and
colorectal cancer.
Tivozanib might represent a promising
anticancer agent in several different
tumor types.