Initial testing of the multitargeted kinase inhibitor pazopanib by the Pediatric Preclinical Testing Program.
Initial testing of the multitargeted kinase inhibitor pazopanib by the Pediatric Preclinical Testing Program.
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DOI：
10.1002/pbc.24016
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发表时间：
2012-09
影响因子：
3.2
通讯作者：
Smith, Malcolm A.
中科院分区：
文献类型：
--
作者：
Keir, Stephen T.;Morton, Christopher L.;Wu, Jianrong;Kurmasheva, Raushan T.;Houghton, Peter J.;Smith, Malcolm A.
帕唑帕尼是一种口服血管生成抑制剂，靶向VEGFR-1、VEGFR-2和VEGFR-3、PDGFR-α、PDGFR-β和KIT，已证实对多种成人癌症异种移植物具有活性。帕唑帕尼以108 mg/kg/天或100 mg/kg每日两次的剂量经口给药28天，对一组儿科横纹肌肉瘤和尤文肉瘤异种移植物进行了测试。虽然没有观察到客观反应，但在大约一半的肉瘤异种移植模型中，与对照组相比，帕唑帕尼诱导了无事件生存期的统计学显著差异。虽然耐受性良好，但帕唑帕尼对评估的肉瘤模型显示出有限的活性，最好的肿瘤反应是生长延迟。
Pazopanib is an oral angiogenesis inhibitor targeting VEGFR-1, -2, and -3, PDGFR-α, PDGFR-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 108mg/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.
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