University of Heidelberg, Mannheim University Medical Center, Interdisciplinary Tumor Center Mannheim, Sarcoma Unit, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Future Oncol. 2011 Dec;7(12):1373-83. doi: 10.2217/fon.11.116.
Pazopanib (GW786034) is a novel, small-molecule tyrosine kinase inhibitor. The primary mechanism of action of pazopanib can be described through its antiangiogenic properties via inhibition of the intracellular tyrosine kinase of VEGF receptor (VEGFR) and PDGF receptor (PDGFR). It is an orally available angiogenesis inhibitor that targets VEGFR-1, -2 and -3, PDGFR-α and -β, and c-kit. Pazopanib exhibits distinct pharmacokinetic and toxicity profiles compared with other agents in that class. Phase I studies defined the recommended monotherapy dose of pazopanib as 800 mg once daily. In 2009, it was approved in the USA for the treatment of advanced and metastatic renal cell carcinoma, and subsequently approved in other countries and demonstrated clinically and statistically significant activity in Phase II and III studies in advanced soft tissue sarcoma patients. This article focuses on its emerging role in the treatment of advanced soft tissue sarcomas.
帕唑帕尼(GW786034)是一种新型小分子酪氨酸激酶抑制剂。帕唑帕尼的主要作用机制可通过其抗血管生成特性来描述,即通过抑制血管内皮生长因子受体(VEGFR)和血小板衍生生长因子受体(PDGFR)的细胞内酪氨酸激酶来实现。它是一种可口服的血管生成抑制剂,可靶向 VEGFR-1、-2 和 -3、PDGFR-α 和 -β 以及 c-kit。与该类别的其他药物相比,帕唑帕尼表现出独特的药代动力学和毒性特征。I 期研究确定帕唑帕尼的推荐单药剂量为 800mg 每日一次。2009 年,它在美国被批准用于治疗晚期和转移性肾细胞癌,随后在其他国家获得批准,并在晚期软组织肉瘤患者的 II 期和 III 期研究中显示出临床和统计学意义上的显著活性。本文重点介绍其在治疗晚期软组织肉瘤方面的新作用。