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      Call for Papers: Digital Platforms and Artificial Intelligence in Dementia

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      Cutaneous Reactions in Pediatric Patients Treated with MEK Inhibitors: A Retrospective Single-Center Study

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          Abstract

          Introduction

          Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors are in use for several indications for adults and children. Cutaneous toxicities are among the most common adverse effects. We aimed to describe the spectrum of cutaneous adverse events, its frequency, and severity in a cohort of pediatric patients.

          Methods

          We reviewed all records of patients in our tertiary treatment center treated with MEK inhibitors between January 2016 and January 2023 for all indications.

          Results

          Among 33 patients, 76% reported cutaneous adverse effects. The highest prevalence was in the group of patients treated with trametinib (90%), followed by the group treated with selumetinib (50%) and the group treated with a combination of trametinib and B-Raf proto-oncogene serine/threonine-protein kinase inhibitor (dabrafenib, 34%). Xerosis, dermatitis, paronychia, and hair heterochromia were most frequently reported. Severity was graded 1 or 2 for most adverse events, and 237 visits to the dermatology clinic related to these adverse events were recorded.

          Conclusions

          Cutaneous adverse events are common in the pediatric population as in adults, but the clinical spectrum is different. Although considered mild, multiple dermatological consultations reflect the distress caused by these events. Dermatologists have a central role in the multidisciplinary care of pediatric patients receiving these agents.

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          Most cited references18

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          Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric BRAF V600–Mutant Low-Grade Glioma

          PURPOSE BRAF V600 mutations occur in many childhood cancers, including approximately 20% of low-grade gliomas (LGGs). Here, we describe a phase I/II study establishing pediatric dosing and pharmacokinetics of trametinib with or without dabrafenib, as well as efficacy and safety in a disease-specific cohort with BRAF V600–mutant LGG; other cohorts will be reported elsewhere. METHODS This is a four-part, phase I/II study (ClinicalTrials.gov identifier: NCT02124772) in patients age 1 patient (part A) included mucosal inflammation (n = 3) and hyponatremia (n = 2). There were no dose-limiting toxicities with combination therapy (part C). The recommended phase II dose of trametinib, with or without dabrafenib, was 0.032 mg/kg once daily for patients age < 6 years and 0.025 mg/kg once daily for patients age ≥ 6 years; dabrafenib dosing in the combination was as previously identified for monotherapy. In 49 patients with BRAF V600–mutant glioma (LGG, n = 47) across all four study parts, independently assessed objective response rates were 15% (95% CI, 1.9 to 45.4) for monotherapy (n = 13) and 25% (95% CI, 12.1 to 42.2) for combination (n = 36). Adverse event–related treatment discontinuations were more common with monotherapy (54% v 22%). CONCLUSION The trial design provided efficient evaluation of pediatric dosing, safety, and efficacy of single-agent and combination targeted therapy. Age-based and weight-based dosing of trametinib with or without dabrafenib achieved target concentrations with manageable safety and demonstrated clinical efficacy and tolerability in BRAF V600–mutant LGG.
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            Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations

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              A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study.

              Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes.

                Author and article information

                Journal
                Dermatology
                Dermatology
                DRM
                DRM
                Dermatology (Basel, Switzerland)
                S. Karger AG (Basel, Switzerland )
                1018-8665
                1421-9832
                22 May 2024
                August 2024
                : 240
                : 4
                : 565-571
                Affiliations
                [a ]Pediatric Dermatology Unit, Schneider Children’s Medical Center, Petah Tiqva, Israel
                [b ]Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
                [c ]Division of Dermatology, Rabin Medical Center, Petah Tiqva, Israel
                [d ]Department of Hematology-Oncology, Schneider Children’s Medical Center, Petah Tiqva, Israel
                Author notes
                Correspondence to: Rivka Friedland, fridland@ 123456tauex.tau.ac.il
                Article
                539374
                10.1159/000539374
                11309057
                38772345
                9e2267fe-2803-4191-b39b-e5af1d8f181d
                © 2024 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 4 October 2023
                : 13 May 2024
                : 2024
                Page count
                Figures: 2, Tables: 1, References: 21, Pages: 7
                Funding
                This study was not supported by any sponsor or funder.
                Categories
                Research Article

                Dermatology
                adverse drug reaction,child,medical oncology
                Dermatology
                adverse drug reaction, child, medical oncology

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