A Proof-of-Concept Assessment of the Safety and Efficacy of Intralesional Diclofenac in the Treatment of Cutaneous Neurofibromas

Mauro Geller,Lisa Oliveira,Aguinaldo Bonalumi Filho,Marcia Gonçalves Ribeiro,David Azulay,Allan Bernacchi,Allan E Rubenstein,Luiz Guilherme Darrigo Jr,Karin Soares Gonçalves Cunha

doi:10.4236/ijcm.2015.612128

Mauro Geller, Lisa Oliveira + Show 7 more

Open Access

https://doi.org/10.4236/ijcm.2015.612128

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Abstract

The objectives of this study were to assess the safety and efficacy of intralesionally administered diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This was a proof-of-concept, prospective, safety and efficacy study of the effect of intralesionally administered diclofenac 25 mg/ml given once a week to 3 target cutaneous neurofibromas for 4 consecutive weeks. Overall, there was no significant change in neurofibroma size. During the study, some treated lesions developed signs of necrosis and fell off after a few weeks, but none of the control neurofibromas fell off. There were no significant changes in patient’s vital signs. A few adverse events occurred, mostly at the injection sites. During the study, some neurofibromas developed necrosis after the diclofenac injections and eventually detached from the patient. Overall, diclofenac was well tolerated, suggesting minimal systemic exposure, which required confirmation and further studies, including bioavailability analysis.

Highlights

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome with highly variable clinical manifestations which have an incidence of approximately 1/4000 worldwide
All subjects were reevaluated during the 7-week duration of the study and, as shown below (Table 1), there were no significant changes in patients’ vital signs throughout the study
All 7 patients presented with abnormal clinical labs during the study, one patient presented a cold and evidence of necrosis in T3, one patient presented some flaccidity in C3, one patient presented asthma, necrosis on neurofibroma on left hip and redness and exulceration in T2 (Table 2)

Summary

Introduction

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome with highly variable clinical manifestations which have an incidence of approximately 1/4000 worldwide. NF1 is extremely variable, with numerous manifestations that may be presented at birth or may develop at any age [1]. The most common lesion in NF1 is the cutaneous neurofibroma, which appears on the skin in 90% of adults with NF1. Cutaneous neurofibromas are benign tumors, presumably of peripheral nerve sheath origin. Their number in an affected individual can range from a few to thousands. Cutaneous neurofibromas are uniformly benign and first appear on the torso around adolescence, but can appear anywhere in the dermis or subcutis [2]

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