title: Tivozanib: practical implications for renal cell carcinoma and other solid tumors.
abstract: Tivozanib is a recently developed, small-molecule tyrosine kinase inhibitor with specific affinity for the vascular endothelial growth factor receptor (VEGFR) family of kinases. Given known relevance of VHL (Von Hippel-Lindau disease tumor suppressor) deregulation in the clear cell variant of renal cell carcinoma, renal cell carcinoma remains an area of interest and subject of recent registration trials with this approach. TIVO-1, a phase III study evaluating tivozanib versus sorafenib in the first-line setting, met its primary endpoint of progression-free survival (11.9 months for tivozanib vs. 9.1 months for sorafenib), with a manageable toxicity profile, leading to formal consideration of regulatory approval in this setting. This review focuses on the preclinical development, pharmacokinetics and early clinical activity of tivozanib in renal cell carcinoma and other solid tumors.
authors.affiliation: University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Berge
authors.forename: D W
authors.initials: DW
authors.lastname: Bowles
authors.forename: T W
authors.initials: TW
authors.lastname: Flaig
authors.forename: E T
authors.initials: ET
authors.lastname: Lam
authors.forename: A
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C553176:tivozanib; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: TIVO; Tivozanib; VEGFR-1 (FLT-1) inhibitors; VEGFR-2 (FLK-1/KDR) inhibitors; VEGFR-3 (FLT-4) inhibitors