Initial testing of the multitargeted kinase inhibitor pazopanib by the pediatric preclinical testing program

Pazopanib is an oral angiogenesis inhibitor targeting vascular growth factor receptor-1, -2, and -3, platelet derived growth factor receptor-a, platelet derived growth factor receptor-beta, 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. Pediatr Blood Cancer 2012;59:586588. (c) 2011 Wiley Periodicals, Inc.