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.).