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A recent phase 1/2 study demonstrated that treatment with the mammalian target of rapamycin inhibitor everolimus reduced subependymal giant cell astrocytoma volume by 30% in 75% of the patients, all of whom were poor candidates for surgical resection. Of the enrolled patients, 4 had had previous surgery to remove subependymal giant cell astrocytoma, and the outcomes for these patients were retrospectively analyzed and are presented here. All 4 experienced over 50% initial reduction in the volume of their subependymal giant cell astrocytoma after 2 to 3 years of therapy with everolimus. Although the volume of 1 patient’s subependymal giant cell astrocytoma returned to baseline volume 36 months after initiating everolimus, they have remained asymptomatic with no recurrent hydrocephalus. Further surgery has been avoided in all cases to date. This course of treatment offers a new and welcome option for these difficult-to-treat patients. [ABSTRACT FROM AUTHOR]

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 period) decreased in 9, did not change in 6, and increased in 1 (median change, −1 seizure; P=0.02). The mean (±SD) score on the validated Quality-of-Life in Childhood Epilepsy questionnaire (on which scores can range from 0 to 100, with higher scores indicating a better quality of life) was improved at 3 months (63.4±12.4) and 6 months (62.1±14.2) over the baseline score (57.8±14.0). Single cases of grade 3 treatment-related sinusitis, pneumonia, viral bronchitis, tooth infection, stomatitis, and leukopenia were reported. Conclusions: Everolimus therapy was associated with marked reduction in the volume of subependymal giant-cell astrocytomas and seizure frequency and may be a potential alternative to neurosurgical resection in some cases, though long-term studies are needed. (Funded by Novartis; ClinicalTrials.gov number, NCT00411619.) N Engl J Med 2010;363:1801-11. [ABSTRACT FROM AUTHOR]