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Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas
- Source :
- Goutagny, S; Raymond, E; Esposito-Farese, M; Trunet, S; Trunet, S; Mawrin, C; et al.(2015). Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas. Journal of Neuro-Oncology. doi: 10.1007/s11060-014-1710-0. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1kh7p2zc
- Publication Year :
- 2015
- Publisher :
- eScholarship, University of California, 2015.
-
Abstract
- © 2015 Springer Science+Business Media New York Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was >20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was >20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume ≥20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3–6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to > 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus.
- Subjects :
- otorhinolaryngologic diseases
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Goutagny, S; Raymond, E; Esposito-Farese, M; Trunet, S; Trunet, S; Mawrin, C; et al.(2015). Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas. Journal of Neuro-Oncology. doi: 10.1007/s11060-014-1710-0. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1kh7p2zc
- Accession number :
- edsair.od.......325..91d03fb4a5872988b53f2422b9966790