title: Tivozanib for the treatment of metastatic renal cancer.
abstract: Tyrosine kinase inhibitors have revolutionized the treatment of metastatic renal cell carcinoma (RCC). Drugs such as sorafenib, sunitinib and pazopanib act on the VEGF receptor pathway, but they can also inhibit other kinases, resulting in off-target toxicities. Tivozanib was developed due to its potency and selectivity against VEGF receptors 1-3. It has a favorable pharmacokinetic profile after oral administration and a long plasma half-life. In the Phase III TIVO-1 trial, it demonstrated a higher response rate and longer progression-free survival than sorafenib with a better side-effect profile. It is currently awaiting approval to be used in the first-line treatment of metastatic RCC. An early-phase trial has also shown its tolerability at full dose when given with the mTOR inhibitor temsirolimus, suggesting its potential in combination treatment. This article examines tivozanib from its laboratory to clinical development, as well as its relevance and future role in the treatment of RCC in the era of the tyrosine kinase inhibitors.
authors.affiliation: Cambridge University Health Partners, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Han Hsi
authors.initials: HH
authors.lastname: Wong
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C553176:tivozanib; C401859:temsirolimus; D040262:Receptors, Vascular Endothelial Growth Factor; D020123:Sirolimus