Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases, in a 4-week-on, 2-week-off schedule in patients with advanced solid tumors

Purpose: To assess the maximum tolerated dose (MTD)/dose-limiting toxicities (DLT), safety, pharmacokinetics, and pharmacodynamics of tivozanib, a potent and selective oralVEGF receptor (VEGFR) tyrosine kinase inhibitor. Experimental Design: Dose levels of 1.0, 1.5, and 2.0 mg/d tivozanib for 28 days followed by 14 days of medication were explored in patients with advanced solid tumors. Results: Forty-one patients were enrolled. Animal data incorrectly predi