EP17.05 CAPECITABINE-INDUCED ACUTE NEUROTOXICITY IN CHARCOT-MARIE-TOOTH DISEASE: CASE REPORT AND MINI-SYSTEMATIC REVIEW

Abstract BACKGROUND Charcot-Marie-Tooth disease (CMT) is a hereditary neuropathy with variable severity, commonly affecting motor and sensory peripheral nerves. In oncology, chemotherapy-induced peripheral neuropathy (CIPN) presents a significant challenge in CMT patients, especially when treated with neurotoxic agents such as oxaliplatin. However, the safety of fluoropyrimidines, particularly capecitabine, in this population is not well characterised. We present a case of early-onset severe neurotoxicity in a CMT patient treated with capecitabine, followed by a mini-systematic literature review. MATERIALS AND METHODS A 51-year-old woman with genetically confirmed CMT1A (PMP22 duplication) and stage III colon adenocarcinoma underwent right hemicolectomy. Due to neuropathy concerns, oxaliplatin was omitted, and she was started on single-agent capecitabine at a 30% dose reduction (875 mg/m²). Within 72 hours of initiation, she developed profound motor weakness. Capecitabine was immediately discontinued, and symptoms rapidly resolved. A mini-systematic review was conducted to evaluate reported capecitabine neurotoxicity in CMT. RESULTS The patient’s rapid-onset quadriparesis reversed within 48 hours of stopping capecitabine. Neurological examination showed no permanent sequelae. She later tolerated 11 cycles of 5-FU/leucovorin and 8 cycles of FOLFIRI without recurrent neurotoxicity. A targeted review of the literature identified around 40 published cases documenting severe neurotoxicity in CMT patients treated with agents such as vincristine, paclitaxel, and cisplatin. Schneider et al. (2017) and Beutler et al. (2014) associated rare variants in CMT-related genes (e.g., SBF2, PRX) with increased susceptibility to taxane-induced neuropathy, even in the absence of overt CMT. Yerushalmi et al. (2007) described irreversible cisplatin-induced neuropathy in a CMT1A patient, whereas Cowie & Barrett (2001) reported safe use in another, highlighting inter-individual variability. Ibañez-Juliá et al. (2018) emphasised the importance of early detection and proposed the SUN-CMT checklist for clinical screening. No prior reports have documented acute, reversible motor neuropathy due to capecitabine in a genetically confirmed CMT patient. CONCLUSION Capecitabine may cause acute and reversible neurotoxicity in patients with Charcot-Marie-Tooth disease, even at reduced doses. Thorough neurological assessment, individualised chemotherapy planning, and multidisciplinary management are essential for minimising treatment-related harm in this population. The absence of specific guidelines for oncological treatment in hereditary neuropathies calls for further prospective studies. Incorporating tools such as the EORTC QLQ-CIPN20 into routine practice may facilitate early detection and intervention for neurotoxicity in high-risk patients.