IJCM  Vol.6 No.12 , December 2015
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-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.
Cite this paper: Geller, M. , Bonalumi Filho, A. , Oliveira, L. , Rubenstein, A. , Darrigo Jr., L. , Azulay, D. , Bernacchi, A. , Ribeiro, M. , Gonçalves Cunha, K. (2015) A Proof-of-Concept Assessment of the Safety and Efficacy of Intralesional Diclofenac in the Treatment of Cutaneous Neurofibromas. International Journal of Clinical Medicine, 6, 975-983. doi: 10.4236/ijcm.2015.612128.

[1]   Geller, M., Mezitis, S.G.E., Nunes, F.P., Ribeiro, M.G., Araújo, A.P.Q.C., Brosntein, M.D., Batista, R.S., Gomes, A.P., Oliveira, L. and Cunha, K.S.G. (2008) Progesterone and Estrogen Receptors in Neurofibromas of Patients with NF1. Journal of Clinical Pathology, 1, 93-97.

[2]   Gutmann, D., Aylsworth, A., Carey, J.C., Korf, B., Marks, J., Pyeritz, R.E., Rubenstein, A. and Viskochil, D. (1997) The Diagnostic Evaluation and Multidisciplinary Management of Neurofibromatosis 1 and Neurofibromatosis 2. JAMA, 278, 51-57.

[3]   Levine, S.M., Levine, E., Taub, P.J. and Weinberg, H. (2008) Electrosurgical Excision Technique for the Treatment of Multiple Cutaneous Lesions in Neurofibromatosis Type I. Journal of Plastic, Reconstructive & Aesthetic Surgery, 61, 958-962.

[4]   Chen, Y.-F., Jobanputra, P., Barton, P., Bryan, S., Fry-Smith, A., Harris, G. and Taylor, R.S. (2008) Cyclooxygenase-2 Selective Non-Steroidal Anti-Inflammatory Drugs (Etodolac, Meloxicam, Celecoxib, Rofecoxib, Etoricoxib, Valdecoxib and Lumiracoxib) for Osteoarthritis and Rheumatoid Arthritis: A Systematic Review and Economic Evaluation. Health Technology Assessment, 12, 1-278.

[5]   Conaghan, P.G. (2012) A Turbulent Decade for NSAIDs: Update on Current Concepts of Classification, Epidemiology, Comparative Efficacy, and Toxicity. Rheumatology International, 32, 1491-1502.

[6]   Pountos, I., Georgouli, T., Calori, G.M. and Giannoudis, P.V. (2012) Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis. Scientific World Journal, 2012, Article ID: 606404.

[7]   Medscape Drug Information: Topical Diclofenac.

[8]   Ong, C.K., Lirk, P., Tan, C.H. and Seymour, R.A. (2007) An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs. Clinical Medicine & Research, 5, 19-34.

[9]   Voltaren® Injection.

[10]   Boyd, K.P., Korf, B.R. and Theos, A. (2009) Neurofibromatosis Type 1. Journal of the American Academy of Dermatology, 61, 1-16.

[11]   Ferner, R.E., Huson, S.M., Thomas, N., Moss, C., Willshaw, H., Evans, D.G., Upadhyaya, M., Towers, R., Gleeson, M., Steiger, C. and Kirby, A. (2007) Guidelines for the Diagnosis and Management of Individuals with Neurofibromatosis 1. Journal of Medical Genetics, 44, 81-88.

[12]   Ferner, R.E. (2007) Neurofibromatosis 1. European Journal of Human Genetics, 15, 131-138.

[13]   Gerber, P.A., Antal, A.S., Neumann, N.J., Homey, B., Matuschek, C., Peiper, M., Budach, W. and Bölke, E. (2009) Neurofibromatosis. European Journal of Medical Research, 14, 102-105.

[14]   Hirsch, N.P., Murphy, A. and Radcliffe, J.J. (2001) Neurofibromatosis: Clinical Presentations and Anaesthetic Implications. British Journal of Anaesthesia, 86, 555-564.

[15]   Williams, V.C., Lucas, J., Babcock, M.A., Gutmann, D.H., Korf, B. and Maria, B.L. (2009) Neurofibromatosis Type 1 Revisited. Pediatrics, 123, 124-132.

[16]   Su, W.H., Cheng, M.H., Lee, W.L., Tsou, T.S., Chang, W.H., Chen, C.S. and Wang, P.H. (2010) Nonsteroidal Anti-Inflammatory Drugs for Wounds: Pain Relief or Excessive Scar Formation? Mediators of Inflammation, 2010, Article ID: 413238.

[17]   Süleyman, H., Demircan, B. and Karagoz, Y. (2007) Anti-Inflammatory and Side Effects of Cyclooxygenase Inhibitors. Pharmacological Reports, 59, 247-258.

[18]   Hofer, M., Pospisil, M., Hoferova, Z., Weiterova, L. and Komurkova, D. (2012) Stimulatory Action of Cyclooxygenase Inhibitors on Hematopoiesis: A Review. Molecules, 17, 5615-5625.