ULTRAMICRONIZED PALMITOYLETHANOLAMIDE FOR CHEMOTHERAPY INDUCED PERIPHERAL NEUROPATHY: A CLINICAL CASE SERIES

C. Morrone¹, A. Diana¹, F. De Vivo¹, F. Piccialli², C. Tuccillo¹, V. Fabbricatore¹, M.B. Passavanti², P. Sansone², V. Pota², M. Fiore², F. Coppolino², M.C. Pace² | ¹Residency Program in Anesthesiology, Resuscitation, Intensive and Pain Therapy University of Campania "Luigi Vanvitelli", Napoli, Italy; ²Department of Women, Child and General and Specialized Surgey, University of Campania "Luigi Vanvitelli", Napoli, Italy

Introduction. Palmitoylethanolamide (PEA) is an endogenous lipid mediator with anti inflammatory and analgesic properties mediated mainly through PPARα activation and modulation of neuroinflammatory pathways (1,2,3). Chemotherapy induced peripheral neuropathy (CIPN), caused by agents such as oxaliplatin, paclitaxel, cisplatin and vincristine, affects up to 80% of patients and is characterized by neuropathic pain, sensory disturbances and functional impairment (2). Given the potential role of neuroinflammation in CIPN, ultramicronized PEA (umPEA), with its improved bioavailability, may represent a promising therapeutic option (2,3).
Methods. We report a two patient case series evaluating the efficacy and tolerability of umPEA in a 60 year old man and a 75 year old woman with B cell non Hodgkin lymphoma who developed progressively worsening chemotherapy induced peripheral neuropathy during antineoplastic treatment. Both patients with CIPN required repeated use of oral fentanyl as rescue analgesia for pain control. Pain intensity was assessed using the Numerical Rating Scale (NRS) and the Douleur Neuropathique en 4 Questions (DN4) questionnaire. Given the significant impact of pain symptoms on patient’s emotional well being, psychological status was also monitored using the Hospital Anxiety and Depression Scale (HADS). In addition to their standard treatment for chronic cancer related pain, patients received oral umPEA 600 mg twice daily for one month, followed by 600 mg once daily for the subsequent two months, administered after meals.
Results. UmPEA was well tolerated in both patients, with no significant adverse effects. One patient experienced clinical improvement within the first week of therapy. NRS decreased from 8 to 3 and DN4 from 7 to 3, allowing discontinuation of rescue oral fentanyl within the first week of treatment. In the second patient, NRS decreased from 8 to 4 and DN4 from 8 to 3, with a progressive reduction in rescue fentanyl use leading to complete discontinuation after approximately 20 days. Concomitant with pain reduction, a marked improvement in HADS scores was observed in both patients, indicating decreased levels of anxiety and depressive symptoms associated with the pain condition. Baseline analgesic therapy remained unchanged throughout the observation period in both cases. Although the small sample size and the concomitant completion of chemotherapy may have contributed to symptom improvement, the early reduction in NRS and DN4 scores observed shortly after umPEA initiation suggests a potential treatment related effect beyond the expected recovery associated with chemotherapy discontinuation.
Conclusion. Despite the small sample, umPEA showed excellent tolerability and meaningful clinical benefits. The rapid and substantial reduction in NRS and DN4 scores observed in these patients suggests that umPEA may help counteract neuroinflammation and peripheral sensitization associated with CIPN. Notably, rescue oral fentanyl was discontinued in both patients without modification of baseline analgesic therapy. However, randomized controlled clinical trials involving larger patient cohorts are warranted to confirm these findings, further establish the therapeutic efficacy of umPEA, and define standardized treatment protocols.