Francesco Baldo1, Antonio Giacomo Grasso2, Luisa Cortellazzo Wiel2, Alessandra Maestro3, Marta Paulina Trojniak3, Flora Maria Murru4, Luca Basso5, Andrea Magnolato6, Irene Bruno6, Egidio Barbi2,6. 1. Department of Medicine, Surgery and Health Sciences, University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy. francescobaldo11@yahoo.it. 2. Department of Medicine, Surgery and Health Sciences, University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy. 3. Pharmacy and Clinical Pharmacology Unit, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/1, 34137, Trieste, Italy. 4. Department of Radiology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/1, 34137, Trieste, Italy. 5. Department of Radiology, Institute for Maternal and Child Health, IRCCS Giannina Gaslini, Via Gerolamo Gaslini 5, 16147, Genova, Italy. 6. Department of Pediatrics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/1, 34137, Trieste, Italy.
Abstract
BACKGROUND: Plexiform neurofibromas (PN) are congenital tumors that affect up to 50% of individuals with neurofibromatosis type 1. Despite their benign nature, they can grow rapidly and cause severe morbidities. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, was reported to induce a clinical response in pediatric subjects with inoperable PN. OBJECTIVE: The aim of this paper is to describe a prospective case series of patients treated with selumetinib with emphasis on drug adverse events. PATIENTS AND METHODS: All the subjects who received selumetinib at the Pediatric Department of Scientific Research Institute and Hospital "Burlo Garofolo", from November 2017 to January 2020, were progressively included. We monitored the patients with a follow-up visit every 3 months. MRI or CT scans to monitor the growth of the tumor were performed after 3 months of treatment, and then every 6-9 months. RESULTS: Selumetinib was prescribed to nine children, with a total of 17 inoperable PN. The mean follow-up period was 12 months. During the follow-up, one patient experienced an ischemic stroke, unrelated to the treatment. Only minor adverse events were observed: six individuals developed gastrointestinal side effects, seven patients presented a mild form of acne, six had paronychia, four developed irritability, and two showed a mild increase in creatine kinase. None of the patients stopped the treatment. Tumor reduction > 20% was recorded in 16 out of 17 PN (94%). One PN remained stable. No tumor growth was recorded during the treatment. CONCLUSIONS: In this case series, selumetinib appears to be effective and safe for the pediatric population.
BACKGROUND: Plexiform neurofibromas (PN) are congenital tumors that affect up to 50% of individuals with neurofibromatosis type 1. Despite their benign nature, they can grow rapidly and cause severe morbidities. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, was reported to induce a clinical response in pediatric subjects with inoperable PN. OBJECTIVE: The aim of this paper is to describe a prospective case series of patients treated with selumetinib with emphasis on drug adverse events. PATIENTS AND METHODS: All the subjects who received selumetinib at the Pediatric Department of Scientific Research Institute and Hospital "Burlo Garofolo", from November 2017 to January 2020, were progressively included. We monitored the patients with a follow-up visit every 3 months. MRI or CT scans to monitor the growth of the tumor were performed after 3 months of treatment, and then every 6-9 months. RESULTS:Selumetinib was prescribed to nine children, with a total of 17 inoperable PN. The mean follow-up period was 12 months. During the follow-up, one patient experienced an ischemic stroke, unrelated to the treatment. Only minor adverse events were observed: six individuals developed gastrointestinal side effects, seven patients presented a mild form of acne, six had paronychia, four developed irritability, and two showed a mild increase in creatine kinase. None of the patients stopped the treatment. Tumor reduction > 20% was recorded in 16 out of 17 PN (94%). One PN remained stable. No tumor growth was recorded during the treatment. CONCLUSIONS: In this case series, selumetinib appears to be effective and safe for the pediatric population.