Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial

• Published in: Neurology Vol. 74; no. 9; p. 762
• Main Authors: Pace, A, Giannarelli, D, Galiè, E, Savarese, A, Carpano, S, Della Giulia, M, Pozzi, A, Silvani, A, Gaviani, P, Scaioli, V, Jandolo, B, Bove, L, Cognetti, F
• Format: Journal Article
• Language: English
• Published: United States 02.03.2010
• Subjects: Adult; Aged; alpha-Tocopherol - administration & dosage; alpha-Tocopherol - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Cisplatin - administration & dosage; Cisplatin - adverse effects; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurologic Examination; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - therapeutic use; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - drug therapy; Risk; Severity of Illness Index; Time Factors; Treatment Outcome
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0b013e3181d5279e

The clinical use of cisplatin chemotherapy is limited by severe peripheral neurotoxicity reported in up to 90% of patients receiving a cumulative dose higher than 300 mg/m(2). The present study evaluates the neuroprotective effect of antioxidant supplementation (vitamin E) in patients treated with cisplatin chemotherapy. A total of 108 patients treated with cisplatin chemotherapy were randomly assigned to receive vitamin E supplementation (alpha-tocopherol 400 mg/day) or placebo. Treatment was started orally before chemotherapy and continued for 3 months after the suspension of cisplatin. Of 108 randomized patients, 68 received at least one clinical and neurophysiologic examination after cisplatin CT; 41 patients received a cumulative dose of cisplatin higher than 300 mg/m(2) and were eligible for statistical analysis: 17 in the vitamin E group (group 1) and 24 in the placebo group (group 2). The incidence of neurotoxicity was significantly lower in group 1 (5.9%) than in group 2 (41.7%) (p < 0.01). The severity of neurotoxicity, measured with a validated neurotoxicity score (Total Neuropathy Score [TNS]), was significantly lower in patients receiving vitamin E than those receiving placebo (mean TNS 1.4 vs 4.1; p < 0.01). This phase III study confirms the neuroprotective role of vitamin E against cisplatin peripheral neurotoxicity. Vitamin E supplementation should be adopted in patients receiving cisplatin-based chemotherapy. This study provides Class II evidence that vitamin E supplementation significantly reduces the relative risk of developing signs or symptoms of neurotoxicity (relative risk = 0.14) (95% confidence interval = 0.02-1.00, p < 0.05).