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

被引:25
|
作者
Keir, Stephen T. [1 ]
Morton, Christopher L. [2 ]
Wu, Jianrong [2 ]
Kurmasheva, Raushan T. [3 ]
Houghton, Peter J. [3 ]
Smith, Malcolm A. [4 ]
机构
[1] Duke Univ, Med Ctr, Durham, NC USA
[2] St Jude Childrens Res Hosp, Memphis, TN 38105 USA
[3] Nationwide Childrens Hosp, Columbus, OH USA
[4] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA
关键词
developmental therapeutics; pazopanib; preclinical testing; MULTIKINASE ANGIOGENESIS INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; PHASE-II; RECURRENT; CARCINOMA; TRIAL;
D O I
10.1002/pbc.24016
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:586 / 588
页数:3
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