title: Initial testing of the multitargeted kinase inhibitor pazopanib by the Pediatric Preclinical Testing Program.
abstract: Pazopanib is an oral angiogenesis inhibitor targeting vascular growth factor receptor-1, -2, and -3, platelet derived growth factor receptor-α, platelet derived growth factor receptor-β, and KIT that has demonstrated activity against a variety of adult cancer xenografts. Pazopanib was tested against a panel of pediatric rhabdomyosarcoma and Ewing sarcoma xenografts at a dose of 108 mg/kg/day or 100 mg/kg twice daily, administered orally for 28 days. While no objective responses were observed, pazopanib induced statistically significant differences in event-free survival compared to controls in approximately one-half of the sarcoma xenograft models tested. Though well tolerated, pazopanib showed limited activity against the sarcoma models evaluated, with the best tumor responses being growth delay.
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA. keir0001@mc.duke.edu
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Keir
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Morton
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.forename: Raushan T
authors.initials: RT
authors.lastname: Kurmasheva
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007191:Indazoles; D051379:Mice; D016513:Mice, SCID; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors; D012208:Rhabdomyosarcoma / Q000188:drug therapy*; D012512:Sarcoma, Ewing / Q000188:drug therapy; D013449:Sulfonamides / Q000627:therapeutic use*; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D042442:Vascular Endothelial Growth Factors; C516667:pazopanib; D020797:Receptor, Platelet-Derived Growth Factor beta