Children's Hospital, China Medical University Hospital, Taichung, Taiwan.
School of Medicine, China Medical University, Taichung, Taiwan.
J Investig Med. 2019 Mar;67(3):686-690. doi: 10.1136/jim-2018-000865. Epub 2018 Nov 18.
Tuberous sclerosis complex (TSC) is a rare disease that causes multisystem benign neoplasm, induced by dysregulation of the mammalian target of the rapamycin pathway (mTOR). This study aimed to examine the effects of continuous low-dose everolimus, a potent and selective inhibitor of mTOR, on the treatment of TSC-associated renal angiomyolipoma (AML). Between July 2013 and August 2017, 11 patients with TSC-AML were enrolled for an everolimus therapy protocol. An oral everolimus dose starting at 2.5 mg daily was gradually increased to 5.0 mg daily. All patients were evaluated using MRI or CT scanning at baseline, 12, 24, 36 and 48 months after the start of treatment for measuring changes of renal AML mass volume. Everolimus therapy resulted in significant shrinkage of TSC-AML volume after 48 months follow-up. Serum levels of everolimus were subdivided into group I (<8 ng/mL, n=6) and group II (>8 ng/mL, n=5). The volume reduction rates were 10.6%-65.2% in group I and 42.5%-70.6% in group II. To evaluate the response to treatment, three of six (50%) were responders in group I, and all the patients in group II (5/5, 100%) were responders. The differences in AML volume reduction between the groups were statistically significant at 12 months (p=0.011), 24 months (p=0006), 36 months (p=0.014) and 48 months (p=0.05). These results suggest that continuous low-dose everolimus therapy (2.5-5 mg daily) might be effective in shrinking TSC-AML volume and minimizes adverse effects and subsequent reducing medical costs.
结节性硬化症复合征（TSC）是一种罕见的疾病，其特征是哺乳动物雷帕霉素靶蛋白（mTOR）通路失调导致多系统良性肿瘤。本研究旨在研究连续低剂量依维莫司（一种强效和选择性 mTOR 抑制剂）对 TSC 相关肾血管平滑肌脂肪瘤（AML）治疗的影响。2013 年 7 月至 2017 年 8 月，11 例 TSC-AML 患者纳入依维莫司治疗方案。起始口服依维莫司剂量为 2.5mg/天，逐渐增加至 5.0mg/天。所有患者在治疗开始后 12、24、36 和 48 个月进行 MRI 或 CT 扫描评估，以测量肾 AML 肿块体积的变化。依维莫司治疗 48 个月后，TSC-AML 体积明显缩小。依维莫司血清水平分为 I 组（<8ng/mL，n=6）和 II 组（>8ng/mL，n=5）。I 组的体积缩小率为 10.6%-65.2%，II 组为 42.5%-70.6%。为评估治疗反应，I 组中 6 例中有 3 例（50%）为应答者，II 组中所有患者（5/5，100%）均为应答者。两组间 AML 体积缩小差异在 12 个月（p=0.011）、24 个月（p=0.006）、36 个月（p=0.014）和 48 个月（p=0.05）时具有统计学意义。这些结果表明，连续低剂量依维莫司治疗（2.5-5mg/天）可能有效缩小 TSC-AML 体积，最大限度地减少不良反应，从而降低医疗费用。
