Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis

作者：Darcy A. Krueger, Marguerite M. Caré, Katherine D. Holland, Karen D. Agricola, Cynthia Tudor, Prajakta Mangeshkar, Kimberly Wilson, Anna W. Byars, Tarek Sahmoud, David Neal Franz · 发表于：New England Journal of Medicine · 年份：2010 · DOI：10.1056/nejmoa1001671 · 被引用次数：1011 · 研究领域：Tuberous Sclerosis Complex Research、Epilepsy research and treatment、Neurofibromatosis and Schwannoma Cases

BACKGROUND: Neurosurgical resection is the standard treatment for subependymal giant-cell astrocytomas in patients with the tuberous sclerosis complex. An alternative may be the use of everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in the tuberous sclerosis complex. METHODS: Patients 3 years of age or older with serial growth of subependymal giant-cell astrocytomas were eligible for this open-label study. The primary efficacy end point was the change in volume of subependymal giant-cell astrocytomas between baseline and 6 months. We gave everolimus orally, at a dose of 3.0 mg per square meter of body-surface area, to achieve a trough concentration of 5 to 15 ng per milliliter. RESULTS: We enrolled 28 patients. Everolimus therapy was associated with a clinically meaningful reduction in volume of the primary subependymal giant-cell astrocytoma, as assessed on independent central review (P<0.001 for baseline vs. 6 months), with a reduction of at least 30% in 21 patients (75%) and at least 50% in 9 patients (32%). Marked reductions were seen within 3 months and were sustained. There were no new lesions, worsening hydrocephalus, evidence of increased intracranial pressure, or necessity for surgical resection or other therapy for subependymal giant-cell astrocytoma. Of the 16 patients for whom 24-hour video electroencephalography data were available, seizure frequency for the 6-month study period (vs. the previous 6-month...