Background: Everolimus at 10 mg daily is approved to treat patients with advanced grade 1/2 neuroendocrine tumors (NETs), although it may lead to significant toxicity. Grade 3 or higher drug-related adverse events and drug discontinuation occur in approximately one-fourth of cases. However, phase I trials have demonstrated that doses from 5 mg daily efficiently inhibit NET cell signaling. Objectives and Methods: This multicenter retrospective study compared the time to treatment failure (TTF) in patients with NETs who received a mean daily dose of 7–10 mg (higher dose [HD]) or ≤6 mg (lower dose [LD]) of everolimus. Results: Ninety-two patients were included: 74 (80%) in the HD group and 18 (20%) in the LD group. At a median follow-up of 4.2 years, the median time to treatment failure (TTF) was 9.2 months for the HD and 7.2 months for the LD groups (p= 0.85). The TTF did not significantly differ between the LD and the HD groups (HR: 1.24; 95% CI: 0.68–2.25;p= 0.47), even after adjusting for age at treatment initiation, the NET grade, and the treatment line. Conclusion: Everolimus doses from 5 to 6 mg/day seem to be equally as effective as higher doses, but lower doses are potentially associated with less toxicity and lower costs. These findings support validation through a randomized clinical trial.
背景：每日10mg依维莫司虽获批用于治疗晚期1/2级神经内分泌肿瘤（NETs），但可能引发显著毒性反应。约四分之一病例出现3级及以上药物相关不良事件及治疗中断。然而，Ⅰ期临床试验证实每日5mg剂量即可有效抑制NET细胞信号传导。目的与方法：本多中心回顾性研究比较了接受依维莫司平均日剂量7-10mg（高剂量组）与≤6mg（低剂量组）的NET患者治疗失败时间（TTF）。结果：共纳入92例患者，其中高剂量组74例（80%），低剂量组18例（20%）。中位随访4.2年后，高剂量组中位TTF为9.2个月，低剂量组为7.2个月（p=0.85）。两组TTF无显著差异（HR：1.24；95% CI：0.68-2.25；p=0.47），即使在调整治疗起始年龄、NET分级和治疗线数后结论依然成立。结论：每日5-6mg依维莫司的疗效与更高剂量相当，且可能具有更低毒性和治疗成本。这些发现支持通过随机临床试验进行验证。
The Efficacy of a Lower Dose of Everolimus in Patients with Advanced Neuroendocrine Tumors
肿瘤(癌症)患者之家