Department of Pediatrics and Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Neurology. 2013 Feb 5;80(6):574-80. doi: 10.1212/WNL.0b013e3182815428. Epub 2013 Jan 16.
To report long-term efficacy and safety data for everolimus for the treatment of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC).
This was an open-label extension phase of a prospective, phase 1-2 trial (NCT00411619) in patients ≥3 years of age with SEGA associated with TSC. Patients received oral everolimus starting at 3 mg/m2 per day and subsequently titrated, subject to tolerability, to attain whole blood trough concentrations of 5-15 ng/mL. Change in SEGA volume, seizures, and safety assessments were the main outcome measures.
Of 28 patients enrolled, 25 were still under treatment at the time of analysis. Median dose was 5.3 mg/m2/day and median treatment duration was 34.2 months (range 4.7-47.1). At all time points (18, 24, 30, and 36 months), primary SEGA volume was reduced by ≥30% from baseline (treatment response) in 65%-79% of patients. All patients reported ≥1 adverse event (AE), mostly grade 1/2 in severity, consistent with that previously reported, and none led to everolimus discontinuation. The most commonly reported drug-related AEs were upper respiratory infections (85.7%), stomatitis (85.7%), sinusitis (46.4%), and otitis media (35.7%). No drug-related grade 4 or 5 events occurred.
Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA.
This study provides Class III evidence that everolimus, titrated to trough serum levels of 5-15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months.
报告依维莫司治疗结节性硬化症相关室管膜下巨细胞星形细胞瘤（SEGA）患者的长期疗效和安全性数据。
这是一项前瞻性、1-2 期试验的开放标签扩展阶段（NCT00411619），纳入年龄≥3 岁、伴有结节性硬化症相关 SEGA 的患者。患者接受依维莫司口服治疗，起始剂量为 3mg/m2/天，随后根据耐受性调整剂量，使全血谷浓度达到 5-15ng/ml。SEGA 体积变化、癫痫发作和安全性评估是主要的观察指标。
28 例患者中，25 例在分析时仍在接受治疗。中位剂量为 5.3mg/m2/天，中位治疗时间为 34.2 个月（范围 4.7-47.1）。在所有时间点（18、24、30 和 36 个月），65%-79%的患者原发性 SEGA 体积从基线下降≥30%（治疗反应）。所有患者均报告了≥1 例不良事件（AE），大多为 1/2 级严重程度，与之前报告的一致，且均未导致依维莫司停药。最常见的药物相关不良事件为上呼吸道感染（85.7%）、口腔炎（85.7%）、鼻窦炎（46.4%）和中耳炎（35.7%）。无药物相关的 4 或 5 级事件发生。
依维莫司治疗结节性硬化症相关 SEGA 患者的长期（中位暴露时间 34.2 个月）治疗是安全有效的。
本研究提供了 III 级证据，表明依维莫司在治疗结节性硬化症相关 SEGA 患者时，剂量调整至 5-15ng/ml 的全血谷浓度，可有效缩小肿瘤体积，中位时间为 34 个月。
