Ospedale San Donato, Medical Oncology , Arezzo, 52100 , Italy
Expert Opin Drug Saf. 2014 Apr;13(4):497-510. doi: 10.1517/14740338.2014.888413.
Axitinib , a highly selective inhibitor of vascular endothelial growth factor receptors taken orally, is approved for second-line treatment of advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine. We review data for axitinib and discuss strategies to manage or prevent adverse events (AEs) and maximize clinical benefit.
A literature search identified key advanced RCC trials of axitinib and other targeted therapies. Each author also contributed a clinical case study to illustrate management approaches in patients who received axitinib following sunitinib in the AXIS Phase III trial. Axitinib has demonstrated a predictable and manageable AE profile in clinical trials; most commonly reported treatment-related events are diarrhea, hypertension, fatigue, nausea, vomiting and dysphonia. Case studies demonstrate that successful management requires patient awareness of potential AEs, regular monitoring and dose modification for specific AEs.
Improvement in progression-free survival with axitinib versus sorafenib in a Phase III trial supports preferred selection of axitinib in the second-line setting. The safety profile of axitinib versus mammalian target of rapamycin inhibitors and sorafenib also provides the opportunity to personalize treatment in advanced RCC based on the likelihood for specific AEs to occur and on prior toxicities in the first-line setting.
阿昔替尼是一种高度选择性的血管内皮生长因子受体抑制剂,可口服,用于索拉非尼或细胞因子治疗失败后的晚期肾细胞癌(RCC)的二线治疗。我们回顾了阿昔替尼的数据,并讨论了管理或预防不良反应(AE)和最大化临床获益的策略。
对阿昔替尼和其他靶向治疗的晚期 RCC 关键试验进行了文献检索。每位作者还贡献了一个临床病例研究,以说明在 AXIS III 期试验中接受索拉非尼后接受阿昔替尼治疗的患者的管理方法。在临床试验中,阿昔替尼表现出可预测和可管理的 AE 特征;最常报告的与治疗相关的事件是腹泻、高血压、疲劳、恶心、呕吐和发音困难。病例研究表明,成功的管理需要患者意识到潜在的 AE,以及对特定 AE 的定期监测和剂量调整。
III 期试验中阿昔替尼与索拉非尼相比改善了无进展生存期,支持在二线治疗中优先选择阿昔替尼。与哺乳动物雷帕霉素靶蛋白抑制剂和索拉非尼相比,阿昔替尼的安全性特征也为基于特定 AE 发生的可能性以及一线治疗中的既往毒性,在晚期 RCC 中进行个体化治疗提供了机会。