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Rapamycin causes regression of astrocytomas in tuberous sclerosis complex
Author(s) -
Franz David Neal,
Leonard Jennifer,
Tudor Cynthia,
Chuck Gail,
Care Marguerite,
Sethuraman Gopalan,
Dinopoulos Argirios,
Thomas George,
Crone Kerry R.
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20784
Subject(s) - tuberous sclerosis , subependymal giant cell astrocytoma , subependymal zone , hydrocephalus , astrocytoma , medicine , pilocytic astrocytoma , magnetic resonance imaging , glioma , radiology , pathology , cancer research
Objective Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the formation of hamartomas in multiple organs. Five to 15% of affected individuals display subependymal giant cell astrocytomas, which can lead to substantial neurological and postoperative morbidity due to the production of hydrocephalus, mass effect, and their typical location adjacent to the foramen of Monro. We sought to see whether therapy with oral rapamycin could affect growth or induce regression in astrocytomas associated with TSC.Methods Five subjects with clinically definite TSC and either subependymal giant cell astrocytomas (n = 4) or a pilocytic astrocytoma (n = 1) were treated with oral rapamycin at standard immunosuppressive doses (serum levels 5–15ng/ml) from 2.5 to 20 months. All lesions demonstrated growth on serial neuroimaging studies. Magnetic resonance imaging scans were performed before and at regular intervals following initiation of therapy.Results All lesions exhibited regression and, in one case, necrosis. Interruption of therapy resulted in regrowth of subependymal giant cell astrocytomas in one patient. Resumption of therapy resulted in further regression. Treatment was well tolerated.Interpretation Oral rapamycin therapy can induce regression of astrocytomas associated with TSC and may offer an alternative to operative therapy of these lesions. Ann Neurol 2006