Department of Pharmacy, Duke University Medical Center, Durham, NC, USA.
Ann Pharmacother. 2011 Jan;45(1):78-83. doi: 10.1345/aph.1M288. Epub 2010 Dec 21.
To review clinical trials and main characteristics of everolimus, with focus on treatment of advanced renal cell carcinoma.
Pertinent data were identified primarily through a search of MEDLINE and PubMed (1966-November 2010) using the primary search terms everolimus, RAD001, renal cell carcinoma, and mTOR inhibitors.
Studies evaluating the safety and efficacy of everolimus in patients with cancer were evaluated, including Phase 1, 2, and 3 trials. Preference was given to Phase 2 and 3 studies evaluating use of everolimus in patients with renal cell carcinoma.
Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor approved for the management of patients with advanced renal cell carcinoma who progressed on tyrosine kinase inhibitor therapy. Actions of everolimus within the mTOR pathway result in decreased protein synthesis and cell cycle arrest, as well as decreased angiogenesis. A usual starting dose for patients with renal cell carcinoma is 10 mg daily. Everolimus undergoes extensive hepatic metabolism, primarily through the CYP3A4 isoenzyme, which predisposes it to drug interactions with inducers and inhibitors of this enzyme. Most commonly reported adverse events associated with everolimus include anemia, hyperglycemia, hypercholesterolemia, mucositis, fatigue, and rash. Approval of everolimus was based on the results of a Phase 3 trial that demonstrated an increase in median progression-free survival by 2.1 months in patients receiving everolimus therapy as compared to placebo. The drug was recently added to the National Comprehensive Cancer Network guidelines as a treatment option for patients with advanced renal cell carcinoma who have progressed on tyrosine kinase therapy.
Based on a review of the currently available literature, everolimus provides a safe and efficacious treatment option for patients with renal cell carcinoma who have progressed on treatment with sunitinib and/or sorafenib.
回顾依维莫司的临床试验和主要特征，重点是治疗晚期肾细胞癌。
主要通过在 MEDLINE 和 PubMed 上搜索（1966 年-2010 年 11 月）使用主要搜索词依维莫司、RAD001、肾细胞癌和 mTOR 抑制剂，来确定相关数据。
评估了依维莫司在癌症患者中的安全性和疗效的研究，包括 1 期、2 期和 3 期试验。优先选择 2 期和 3 期研究，评估依维莫司在肾细胞癌患者中的应用。
依维莫司是一种口服哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂，被批准用于治疗接受酪氨酸激酶抑制剂治疗后进展的晚期肾细胞癌患者。依维莫司在 mTOR 途径中的作用导致蛋白质合成和细胞周期停滞减少，以及血管生成减少。肾细胞癌患者的常用起始剂量为每天 10mg。依维莫司经历广泛的肝代谢，主要通过 CYP3A4 同工酶，这使其易受该酶诱导剂和抑制剂的药物相互作用的影响。与依维莫司相关的最常见不良反应包括贫血、高血糖、高胆固醇血症、黏膜炎、疲劳和皮疹。依维莫司的批准是基于一项 3 期试验的结果，该试验表明，与安慰剂相比，接受依维莫司治疗的患者中位无进展生存期延长了 2.1 个月。该药物最近被纳入国家综合癌症网络指南，作为接受舒尼替尼和/或索拉非尼治疗后进展的晚期肾细胞癌患者的治疗选择。
基于对现有文献的回顾，依维莫司为接受舒尼替尼和/或索拉非尼治疗后进展的肾细胞癌患者提供了一种安全有效的治疗选择。
