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Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis.
- Source :
-
The New England journal of medicine [N Engl J Med] 2010 Nov 04; Vol. 363 (19), pp. 1801-11. - Publication Year :
- 2010
-
Abstract
- 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.<br />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.<br />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.<br />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.).
- Subjects :
- Administration, Oral
Adolescent
Adult
Angiofibroma drug therapy
Anticonvulsants therapeutic use
Astrocytoma etiology
Astrocytoma pathology
Brain Neoplasms etiology
Brain Neoplasms pathology
Child
Child, Preschool
Cognition drug effects
Drug Therapy, Combination
Everolimus
Facial Neoplasms drug therapy
Female
Humans
Male
Prospective Studies
Quality of Life
Seizures etiology
Sirolimus administration & dosage
Sirolimus adverse effects
Sirolimus pharmacokinetics
TOR Serine-Threonine Kinases
Tuberous Sclerosis complications
Young Adult
Astrocytoma drug therapy
Brain Neoplasms drug therapy
Intracellular Signaling Peptides and Proteins antagonists & inhibitors
Protein Serine-Threonine Kinases antagonists & inhibitors
Seizures drug therapy
Sirolimus analogs & derivatives
Tuberous Sclerosis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 363
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 21047224
- Full Text :
- https://doi.org/10.1056/NEJMoa1001671