The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1
The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1
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DOI：
10.1093/ndt/gfu013
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发表时间：
2014-06-01
影响因子：
6.1
通讯作者：
Franz, David N.
中科院分区：
文献类型：
--
作者：
Kingswood, J. Chris;Jozwiak, Sergiusz;Franz, David N.
结节性硬化症(TSC)的特点是多个器官的良性肿瘤，包括大脑、肾脏、皮肤、肺和心脏。我们的目标是评价mTOR抑制剂依维莫司对室管膜下巨细胞星形细胞瘤(SEGA)合并TSC患者血管肌脂肪瘤的治疗作用。在结节性硬化症复合体-1(NCT00789828)研究中应用伊维莫司，这是一项前瞻性、双盲、随机、安慰剂对照的3期研究，研究了伊维莫司治疗SEGA与TSC相关的疗效。从基线前到基线SEGA连续增长的患者被随机分配(2：1)接受4.5 mg/m(2)/d的伊波利莫(目标血谷：5-15 ng/mL；n=78)或安慰剂(n=39)。分析了目标基线血管肌脂肪瘤病变(1/1000日元；最大直径1/1000日元1.0 cm)的患者(n=44)的血管肌肉脂肪瘤有效率。在基线、12周、24周和48周以及每年通过肾脏CT或MRI筛查来评估血管肌肉脂肪瘤的有效率，血管肌肉脂肪瘤有效率在接受依维莫司和安慰剂治疗的患者中分别为53.3%(16/30)和0(0/14)。血管肌肉脂肪瘤在12周、24周和48周时仅在服用依维莫司的患者(56.5%、78.3%和80.0%)中出现，而安慰剂治疗的患者(在每个时间点均为0%)仅在所有目标病变的总体积中减少千分之50。在同一时间点，接受伊波利莫司治疗的患者血管肌脂肪瘤缩小千分之30%的比例更高(分别为82.6、100和100%，与安慰剂组相比分别为8.3、18.2和16.7%)。在SEGA合并TSC的患者中，伊波利莫斯显示出有效的血管肌肉脂肪瘤缩小体积。
Tuberous sclerosis complex (TSC) is characterized by benign tumours in multiple organs, including the brain, kidneys, skin, lungs and heart. Our objective was to evaluate everolimus, an mTOR inhibitor, in the treatment of angiomyolipoma in patients with subependymal giant cell astrocytoma (SEGA) associated with TSC.EXamining everolimus In a Study of Tuberous Sclerosis Complex-1 (NCT00789828), a prospective, double-blind, randomized, placebo-controlled, Phase 3 study, examined everolimus in treating SEGA associated with TSC. Patients with serial SEGA growth from pre-baseline to baseline scans were randomly assigned (2:1) to receive 4.5 mg/m(2)/day everolimus (target blood trough: 5-15 ng/mL; n = 78) or placebo (n = 39). Angiomyolipoma response rates were analysed in patients (n = 44) with target baseline angiomyolipoma lesions (a parts per thousand yen1 angiomyolipoma; longest diameter a parts per thousand yen1.0 cm). An angiomyolipoma response rate, defined as the proportion of patients with confirmed angiomyolipoma response, was assessed by kidney CT or MRI screening at baseline, at 12, 24 and 48 weeks and annually.Angiomyolipoma response rates were 53.3% (16/30) and 0% (0/14) for everolimus- and placebo-treated patients, respectively. Angiomyolipoma reductions a parts per thousand yen50% in the sum of volumes of all target lesions were seen only in everolimus-treated patients (56.5, 78.3 and 80.0%) compared with placebo-treated patients (0% at each time point) at Weeks 12, 24 and 48, respectively. Greater percentages of everolimus-treated patients had angiomyolipoma reductions a parts per thousand yen30% at these same time points (82.6, 100 and 100% versus 8.3, 18.2 and 16.7% for everolimus versus placebo, respectively).Everolimus showed efficacy in reducing angiomyolipoma lesion volume in patients with SEGA associated with TSC.