Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
Ann Pharmacother. 2012 Sep;46(9):1212-9. doi: 10.1345/aph.1R087. Epub 2012 Sep 4.
To present the current clinical evidence on everolimus for use in pancreatic neuroendocrine tumors (pNET).
A literature search was performed using PubMed and MEDLINE (1946-March 2012). Search terms were everolimus, RAD001, mTOR inhibitor, and pancreatic neuroendocrine tumors. Abstracts from the American Society of Clinical Oncology 2000-2012 meetings and Food and Drug Administration (FDA) reviews were searched to obtain otherwise unpublished data. The national clinical trials registry was searched for current and future studies of everolimus in pNET.
Clinical studies available in the English language describing the pharmacology, pharmacokinetics, clinical activity, and safety of everolimus in pNET were included. All peer-reviewed, clinically relevant publications were reviewed for inclusion.
Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor approved by the FDA in May 2011 for the treatment of progressive, advanced pNET. Everolimus exerts its effect by inhibiting multiple downstream pathways of mTOR, which decreases cell proliferation, survival, and angiogenesis. Its pNET indication was based on the results of RADIANT-3, a Phase 3 trial demonstrating increased median progression-free survival (11 months) with everolimus 10 mg orally once daily compared to placebo (4.6 months). Everolimus was well tolerated in clinical trials. The most commonly reported adverse events included stomatitis, rash, diarrhea, fatigue, infections, nausea, and decreased appetite. Grade 3/4 events including anemia, thrombocytopenia, pneumonitis, and hyperglycemia occurred in approximately 5% of patients.
Based on review of the available literature, everolimus is a safe and effective treatment option for patients with low- to intermediate-grade, unresectable or metastatic pNET that have progressed on prior therapies. Until results of head-to-head, randomized controlled trials are conducted to compare everolimus to other treatment options, it cannot be said whether everolimus is more efficacious or tolerable than other treatment options.
介绍依维莫司在胰腺神经内分泌肿瘤（pNET）中的临床应用证据。
通过PubMed 和 MEDLINE（1946 年至 2012 年 3 月）进行文献检索。检索词为依维莫司、RAD001、mTOR 抑制剂和胰腺神经内分泌肿瘤。检索美国临床肿瘤学会 2000-2012 年会议和美国食品药品监督管理局（FDA）的综述，以获取其他未发表的数据。检索国家临床试验注册处，以获取依维莫司在 pNET 中的当前和未来研究。
纳入了描述依维莫司在 pNET 中的药理学、药代动力学、临床活性和安全性的英语临床研究。所有经同行评审的、具有临床相关性的出版物均进行了审查，以纳入研究。
依维莫司是一种口服哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂，于 2011 年 5 月获得 FDA 批准用于治疗进展性、晚期 pNET。依维莫司通过抑制 mTOR 的多个下游通路发挥作用，从而减少细胞增殖、存活和血管生成。其 pNET 适应证是基于 RADIANT-3 期临床试验的结果，该试验表明依维莫司 10mg 口服，每日一次，与安慰剂（4.6 个月）相比，中位无进展生存期（11 个月）延长。依维莫司在临床试验中耐受性良好。最常见的不良反应包括口炎、皮疹、腹泻、疲劳、感染、恶心和食欲下降。约 5%的患者发生 3/4 级事件，包括贫血、血小板减少症、肺炎和高血糖。
基于对现有文献的回顾，依维莫司是一种安全有效的治疗选择，适用于低至中级别、无法切除或转移性 pNET 患者，这些患者在先前治疗中已进展。在进行头对头、随机对照试验比较依维莫司与其他治疗选择之前，不能说依维莫司比其他治疗选择更有效或更耐受。
