Milestones for development of tivozanib for kidney cancer therapy

In the May 10, 2012 issue of the Journal of Clinical Oncology,
Nosov and colleagues report on a company-sponsored
(AVEO), phase II randomized discontinuation trial (RDT)
of tivozanib therapy for metastatic kidney cancer (1).
This trial is part of a development of tivozanib seeking to
expand the growing list of active medical treatment options
blocking the vascular endothelial growth factor (VEGF)
pathway, besides drugs with mammalian target of rapamycin
(mTOR) pathway inhibition, and treatments using immune
mechanisms. Among the VEGF pathway approaches,
small molecule tyrosine kinase (TKI) inhibitors already
approved for use in metastatic renal cell carcinoma include
sunitinib, sorafenib, pazopanib, and most recently axitinib;
bevacizumab is an antibody that binds plasma VEGF, so that
the VEGF receptor remains without this ligand. Tivozanib
is distinguished from the other small molecule VEGFR
TKI by a more potent inhibition of VEGF receptors 1, 2
and 3 (half-maximal inhibition at 0.24 nmol/L or lower), and
a long half-life (reported here at 87.0±27.9 hours) (1).