Potential prevention and treatment of oxaliplatin associated peripheral neuropathy

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8093 Background: The major toxicities of oxaliplatin are two different types of peripheral neuropathies, a reversible one related to the drug's infusion and an irreversible one based on the cumulative dose received.The incidence of onset and the severity of the neuropathy increase as the number of cycles increase as does the prevalence of the toxicity. Gabapentin (Neurontin) and carbamazepine (Tegretol) are two drugs used in the treatment of autonomic dysfunction and peripheral neuropathic pain. Given the similar syndromes, a trial was first conducted to see if the use of these agents could prevent the progression of this oxaliplatin-associated toxicity. A second trial was then begun to see if these agents could totally prevent oxaliplatin-associated neurotoxicity. Methods: 34 consecutive patients receiving oxaliplatin-5-FU-leukovorin rescue chemotherapy for stage IV colon cancer were available for study. Treatment was determined by random drawing of treatment options. Results: In the intial study of 24 patients, grade 1 toxicity had to be reported before treatment was intiated with either drug, usually after the 2nd cycle. Treatment was begun a week before the 3rd cycle. Gabapentin was begun at 900 mg/day and escalated to 2700 mg/day, as needed. Carbamazepine was begun at 400 mg/day and escalated to 800 mg/day, as needed. A success rate for preventing any grade 3 or higher sensory symptomatology occurred in 75% (9/12) in both groups. No life-threatening nor persistent neuropathy occurred. To judge whether these agents could totally prevent the sensory neuropathy, the next 10 patients have been randomized at the start of their treatment to either gabapentin, carbamazepine or nothing. After 3 cycles the 6 treated patients have grade 1 sensory neuropathy while 2 of the 4 non-prophylaxed patients had grade 2 sensory neuropathy and were started on therapy before cycle 3. No drug toxicity associated with either carbamazepine or gabapentin was observed. Conclusions: While a prospective, double-blinded randomized trial needs to confirm these findings, gabapentin or carbamazepine can be considered as adjuvant therapy to minimize the sensory neuropathic toxicity of oxaliplatin. No significant financial relationships to disclose.