Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas Journal Article


Authors: Karajannis, M. A.; Legault, G.; Hagiwara, M.; Giancotti, F. G.; Filatov, A.; Derman, A.; Hochman, T.; Goldberg, J. D.; Vega, E.; Wisoff, J. H.; Golfinos, J. G.; Merkelson, A.; Roland, J. T.; Allen, J. C.
Article Title: Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas
Abstract: BackgroundActivation of the mammalian target of rapamycin (mTOR) signaling pathway is thought to be a key driver of tumor growth in Merlin (NF2)-deficient tumors. Everolimus is an oral inhibitor of mTOR complex 1 (mTORC1) with antitumor activity in a variety of cancers.MethodsWe conducted a single-institution, prospective, 2-stage, open-label phase II study to estimate the response rate to everolimus in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannoma (VS). Ten eligible patients were enrolled, including 2 pediatric patients. Everolimus was administered at a daily dose of 10 mg (adults) or 5 mg/m2/day (children <18 y) orally in continuous 28-day courses, for up to 12 courses. Response was assessed every 3 months with MRI, using 3-dimensional volumetric tumor analysis, and audiograms. Nine patients were evaluable for the primary response, defined as ≥15% decrease in VS volume. Hearing response was evaluable as a secondary endpoint in 8 patients.ResultsNone of the 9 patients with evaluable disease experienced a clinical or MRI response. No objective imaging or hearing responses were observed in stage 1 of the trial, and the study was closed according to predefined stopping rules.ConclusionEverolimus is ineffective for the treatment of progressive VS in NF2 patients. We are currently conducting a pharmacokinetic/pharmacodynamic ("phase 0") study of everolimus in presurgical VS patients to elucidate the biological basis for apparent treatment resistance to mTORC1 inhibition in these tumors. © 2013 © The Author(s) 2013.
Keywords: mammalian target of rapamycin; everolimus; phase ii trial; neurofibromatosis type 2; vestibular schwannoma.
Journal Title: Neuro-Oncology
Volume: 16
Issue: 2
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2014-01-01
Start Page: 292
End Page: 297
Language: English
DOI: 10.1093/neuonc/not150
PROVIDER: scopus
PMCID: PMC3895376
PUBMED: 24311643
DOI/URL:
Notes: Export Date: 3 March 2014 -- CODEN: NEURJ -- Source: Scopus
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