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

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-ofconcept, 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 * Corresponding author. M. Geller et al. 976 studies, including bioavailability analysis.

Cutaneous neurofibromas in the genomics era: current understanding and open questions

“…One such study assessed diclofenac, a nonsteroidal anti-inflammatory drug, in cNF patients. 111 The study did not show a conclusive change in neurofibroma size; in some cases, the neurofibromas grew, while in other cases the cNFs presented with necrosis and detached. These results appear to serve as a proof-of-concept for a study that will investigate topical diclofenac following laser microporation of cNFs.…”

Clinical assessment of the use of topical liquid diclofenac following laser microporation of cutaneous neurofibromas in individuals with neurofibromatosis type 1

“…In this study, some treated cNFs experienced inflammation, tissue necrosis, and full or partial detachment. These events were not observed in the control cNFs [22]. These findings justify additional investigation into the efficacy of using diclofenac to treat cNFs in the search for the most convenient drug delivery system.…”

“…To our knowledge, this is the first study using topical diclofenac for the treatment of cutaneous neurofibromas. Topical administration of diclofenac and other drugs is an alternative to oral administration offering potential advantages of greater ease of application and a more favorable safety profile [30], and, in the case of cNF treatment, an alternative to intralesional treatment [22]. However, in order for the efficacy of topical administration of a drug to be comparable to other routes of administration, it is necessary for the drug to have the ability to penetrate the dermis and present a permeation at the target site at concentrations sufficient for a therapeutic effect to be established.…”

“…The inclusion criteria included patients with a clinical diagnosis of NF1 according to the NIH Consensus Development Conference NF1 diagnostic criteria (NIH, 1998) and had four or more cNFs measuring 0.5-1.2 cm in greatest diameter present on either the thorax, abdomen, and upper or lower limbs (measured in a single plane). In keeping with the previous study [22], seven patients initially satisfied these inclusion criteria and six were enrolled in the study (one patient was unable to participate due to an unrelated family matter).…”

“…Although cNFs are easily accessible lesions, the formulation of topical diclofenac gel would likely be unable to adequately penetrate these benign tumors because of the barrier function of the skin's corneal layer, a known limiting factor for passive drug penetration and transdermal drug delivery [23]. Laser microporation followed by topical application of liquid diclofenac may offer an alternative delivery method, while providing the benefit of administering a significantly smaller dose of diclofenac as compared to oral or intralesional treatment [22]. Furthermore, topical application of the treatment may be applied at home by the patient painlessly and at less final cost to the patient, with greater safety.…”