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Selumetinib in the Treatment of Symptomatic Intractable Plexiform Neurofibromas in Neurofibromatosis Type 1: A Prospective Case Series with Emphasis on Side Effects

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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.

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Acknowledgements

The authors thank Martina Bradaschia MD, for the linguistic revision of the manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine, Surgery and Health Sciences, University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy

    Francesco Baldo, Antonio Giacomo Grasso, Luisa Cortellazzo Wiel & Egidio Barbi

  2. Pharmacy and Clinical Pharmacology Unit, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell’Istria 65/1, 34137, Trieste, Italy

    Alessandra Maestro & Marta Paulina Trojniak

  3. Department of Radiology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell’Istria 65/1, 34137, Trieste, Italy

    Flora Maria Murru

  4. Department of Radiology, Institute for Maternal and Child Health, IRCCS Giannina Gaslini, Via Gerolamo Gaslini 5, 16147, Genova, Italy

    Luca Basso

  5. Department of Pediatrics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell’Istria 65/1, 34137, Trieste, Italy

    Andrea Magnolato, Irene Bruno & Egidio Barbi

Authors
  1. Francesco Baldo
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  2. Antonio Giacomo Grasso
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  3. Luisa Cortellazzo Wiel
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  4. Alessandra Maestro
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  6. Flora Maria Murru
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  7. Luca Basso
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  8. Andrea Magnolato
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  9. Irene Bruno
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Contributions

FB collected and processed the data and wrote the manuscript. FB and AGG reviewed the literature. AGG and LCW co-wrote the manuscript. FMM and LB selected the clinical images. AM, MPPT, AM, IB, and EB reviewed the manuscript.

Corresponding author

Correspondence to Francesco Baldo.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Francesco Baldo, Antonio Giacomo Grasso, Luisa Cortellazzo Wiel, Alessandra Maestro, Marta Paulina Trojniak, Flora Maria Murru, Luca Basso, Andrea Magnolato, Irene Bruno, and Egidio Barbi declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethical approval

Approval was obtained from the ethics committee of our Institute.

Consent to participate

A written consent to participate was signed by all the subjects involved and/or their parents.

Consent for publication

A written consent for publication was signed by all the subjects involved and/or their parents.

Availability of data and material

All relevant data are included in the article and/or its supplementary information files. All other data supporting the study (such as radiological photos or images) are available from the corresponding author upon request.

Code availability

Data were collected and elaborated with Microsoft Office Excel.

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Baldo, F., Grasso, A.G., Cortellazzo Wiel, L. et al. Selumetinib in the Treatment of Symptomatic Intractable Plexiform Neurofibromas in Neurofibromatosis Type 1: A Prospective Case Series with Emphasis on Side Effects. Pediatr Drugs 22, 417–423 (2020). https://doi.org/10.1007/s40272-020-00399-y

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  • DOI: https://doi.org/10.1007/s40272-020-00399-y

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