Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

Autor:	Kim H; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Yoon HM; Department of Radiology and Research Institute of Radiology, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kim EK; Department of Plastic Surgery, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Ra YS; Department of Neurosurgery, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kim HW; Department of Psychiatry, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Yum MS; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kim MJ; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Baek JS; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Sung YS; Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea., Lee SM; Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Lim HS; Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Lee BJ; Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Lim HT; Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.; Orthopia Eye Clinic, Seoul, Republic of Korea., Kim D; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Yoon J; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Bae H; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Hwang S; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Choi YH; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kim KA; Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Choi IH; Department of Genetic Counseling, University of Ulsan College of Medicine, Seoul, Republic of Korea., Lee SW; Radiation Oncology Laboratory, University of Ulsan College of Medicine, Seoul, Republic of Korea., Park SJ; School of Korean Medicine, Pusan National University, Pusan, Korea., Lee BH; Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.; Orthopia Eye Clinic, Seoul, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2024 Jul 08. Date of Electronic Publication: 2024 Jul 08.
DOI:	10.1093/neuonc/noae121
Abstrakt:	Background: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. Methods: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. Results: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. Conclusion: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
Databáze:	MEDLINE
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