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替沃扎尼:对肾细胞癌及其他实体瘤的实际意义。

Tivozanib: practical implications for renal cell carcinoma and other solid tumors.

作者信息

Berge E M, Bowles D W, Flaig T W, Lam E T, Jimeno A

机构信息

University of Colorado School of Medicine, Denver, CO, USA.

出版信息

Drugs Today (Barc). 2013 May;49(5):303-15. doi: 10.1358/dot.2013.49.5.1960218.

Abstract

Tivozanib is a recently developed, small-molecule tyrosine kinase inhibitor with specific affinity for the vascular endothelial growth factor receptor (VEGFR) family of kinases. Given known relevance of VHL (Von Hippel-Lindau disease tumor suppressor) deregulation in the clear cell variant of renal cell carcinoma, renal cell carcinoma remains an area of interest and subject of recent registration trials with this approach. TIVO-1, a phase III study evaluating tivozanib versus sorafenib in the first-line setting, met its primary endpoint of progression-free survival (11.9 months for tivozanib vs. 9.1 months for sorafenib), with a manageable toxicity profile, leading to formal consideration of regulatory approval in this setting. This review focuses on the preclinical development, pharmacokinetics and early clinical activity of tivozanib in renal cell carcinoma and other solid tumors.

摘要

替沃扎尼是一种最近开发的小分子酪氨酸激酶抑制剂,对血管内皮生长因子受体(VEGFR)激酶家族具有特异性亲和力。鉴于已知VHL(冯·希佩尔-林道病肿瘤抑制因子)失调在肾细胞癌透明细胞变体中的相关性,肾细胞癌仍然是一个受关注的领域,并且是该方法近期注册试验的主题。TIVO-1是一项在一线治疗中评估替沃扎尼与索拉非尼对比的III期研究,达到了其无进展生存期的主要终点(替沃扎尼为11.9个月,索拉非尼为9.1个月),毒性特征可控,促使在此情况下正式考虑监管批准。本综述重点关注替沃扎尼在肾细胞癌和其他实体瘤中的临床前开发、药代动力学和早期临床活性。

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