Acute oxaliplatin-induced peripheral nerve hyperexcitability

Purpose: Oxaliplatin is a novel platinum compound with clinical activity in several malignancies. Neurotox-icity is dose-limiting and occurs in two distinct forms, an acute neurologic symptom complex that occurs within hours or days of therapy and a chronic, cumulative sensory neuropathy. Patients and Methods: Patients were treated in a phase I study designed to establish the maximum-tolerated dose of capecitabine given with oxaliplatin. Because of the unusual neurosensory toxicity of oxali-platin, detailed neurologic examination, needle electro-myography (EMG), and nerve conduction studies (NCS) were performed before and the day after oxaliplatin in a subset of 13 patients. Carbamazepine therapy was tried in 12 additional patients to determine whether the neurologic effects might be relieved. Results: All patients experienced acute, reversible neurotoxicities with oxaliplatin. Symptoms included paresthesias, dysesthesias, cold hypersensitivity, jaw pain, eye pain, pain in the arm used for drug infusion, ptosis, leg cramps, and visual and voice changes. Serial EMG and NCS revealed striking signs of hyperexcitabil-ity in motor nerves after oxaliplatin. In patients who achieved therapeutic levels, carbamazepine did not alter the clinical or electromyographic abnormalities. Conclusion: The acute neurotoxicity seen with oxali-platin is characterized by peripheral-nerve hyperexcit-ability, and the findings are similar to the clinical man-ifestations of neuromyotonia. Carbamezepine, which provides symptomatic relief in acquired neuromytonia, did not seem to be beneficial. Efforts to identify a successful neuroprotectant strategy would have a ma-jor impact on improving patient quality of life and the ability to deliver full doses of oxaliplatin