title: Pazopanib: a review of its use in the management of advanced renal cell carcinoma.
abstract: Pazopanib (Votrient(®)) is an orally administered multi-tyrosine kinase inhibitor that is approved in the EU, the US and other countries for the treatment of advanced renal cell carcinoma. Pazopanib predominantly inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β, and the stem cell factor receptor c-Kit, resulting in inhibition of tumour angiogenesis, cell growth and survival. In randomized controlled trials in patients with advanced, predominantly clear-cell, renal cell carcinoma, progression-free survival (PFS) and the objective response rate were significantly greater in pazopanib recipients than in placebo recipients (VEG105192 trial), and pazopanib was noninferior to sunitinib with respect to PFS (COMPARZ study). In a patient-preference, crossover study involving 10 weeks of treatment with each drug (PISCES study), significantly more patients expressed a preference for pazopanib than for sunitinib, with their preference being based primarily on tolerability and quality-of-life issues. Health-related quality-of-life (HR-QOL) assessments generally favoured pazopanib over sunitinib in COMPARZ, and pazopanib did not cause deterioration in HR-QOL compared with placebo in VEG105192. Pazopanib caused less myelosuppression, hand-foot syndrome, mucositis/stomatitis, dysgeusia and fatigue than sunitinib, but more abnormal liver function tests. Therefore, pazopanib was noninferior to sunitinib with respect to efficacy in the treatment of advanced renal cell carcinoma, but had a differentiated tolerability profile, which affected HR-QOL and patient preference.
authors.affiliation: Adis, Level 1, 5 The Warehouse Way, Northcote 0627; Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand, demail@springer.com.
authors.forename: Paul L
authors.initials: PL
authors.lastname: McCormack
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007191:Indazoles; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011788:Quality of Life; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D011505:Protein-Tyrosine Kinases