Oxaliplatin-induced neurotoxicity and the development of neuropathy

The pathophysiology of oxaliplatin‐induced neurotoxicity remains unclear, although in vitro studies suggest involvement of voltage‐gated Na+ channels. In the present study, clinical assessment was combined with nerve conduction studies (NCS) and nerve excitability studies in 16 patients after completion of oxaliplatin therapy. Chronic neuropathic symptoms persisted in 50% of patients. NCS confirmed abnormalities in symptomatic patients: sensory potentials were significantly low, whereas motor studies remained essentially normal. At 12‐month follow‐up of symptomatic patients, positive sensory symptoms improved but NCS abnormalities persisted. Cumulative oxaliplatin dose was a predictor of neuropathy, and long‐term effects appeared to be minimized by low single‐infusion dosages. Nerve excitability measures in symptomatic patients established that axons were of high threshold. Refractoriness was significantly greater in patients (symptomatic group, 56.3 ± 24.9%; entire patient group, 46.3 ± 12.5%; controls, 27.1 ± 1.9%; P < 0.05). Thus, although positive sensory symptoms of oxaliplatin‐induced neuropathy improved, negative sensory symptoms and abnormalities of sensory nerve conduction persisted. Differences in nerve excitability measures, particularly refractoriness, support in vitro studies indicating involvement of voltage‐gated transient Na+‐channel dysfunction in the development of oxaliplatin‐induced neurotoxicity. Muscle Nerve, 2005