The MEK inhibitor selumetinib reduces spinal neurofibroma burden in patients with NF1 and plexiform neurofibromas.

Autor:	Jackson S; Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, Bethesda, Maryland, USA.; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Baker EH; Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA., Gross AM; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Whitcomb P; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Baldwin A; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Derdak J; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Tibery C; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Desanto J; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Carbonell A; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Yohay K; Departments of Neurology and Pediatrics, NYU Langone Health, New York, New York, USA., O'Sullivan G; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland, USA., Chen AP; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland, USA., Widemann BC; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA., Dombi E; Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology advances [Neurooncol Adv] 2020 Aug 08; Vol. 2 (1), pp. vdaa095. Date of Electronic Publication: 2020 Aug 08 (Print Publication: 2020).
DOI:	10.1093/noajnl/vdaa095
Abstrakt:	Background: Spinal neurofibromas (SNFs) in neurofibromatosis type 1 (NF1) can cause progressive spinal cord compression and neurological dysfunction. The MEK inhibitor selumetinib shrinks the majority of plexiform neurofibromas (PNs) in patients with NF1. We assessed the effect of selumetinib on SNF. Methods: Pediatric and adult patients with NF1 and inoperable PN participating in phase 2 studies of selumetinib for PN were included in this analysis if they had SNF and serial spine magnetic resonance imaging (MRI). Selumetinib was administered orally at the recommended dose of 25 mg/m 2 /dose twice daily (max 50 mg b.i.d.; 1 cycle = 28 days). We qualitatively assessed the effect of selumetinib on SNF-related spinal canal distortion, cerebrospinal fluid distribution, and spinal cord deformity on MRI. Results: Twenty-four patients (18 male), median age 16.9 years (range, 6.2-60.3), had SNF, 22 of which were associated with the same nerves as the target PN assessed on the clinical trial. Twenty patients had spinal cord deformity. Twenty-three patients completed at least 12 treatment cycles to date. Eighteen patients showed subtle to a marked improvement in SNF burden, 5 remained stable, and no worsening was observed during treatment. Conclusions: This is the first study describing the effect of selumetinib on SNF. Of 24 patients, 18 exhibited some improvement of SNF burden on imaging. These findings suggest that selumetinib may prevent the worsening of cord compression, potentially reducing the need for surgical interventions in select patients or benefitting patients who do not have a surgical option. Prospective evaluation of the clinical benefit of selumetinib for SNF is warranted. (Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology 2020.)
Databáze:	MEDLINE
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