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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.


METHODS
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).
Pace
A
A
Department of Neuroscience, Regina Elena National Cancer Institute, 00144 Rome, Italy. pace@ifo.it
Giannarelli
D
D
Galiè
E
E
Savarese
A
A
Carpano
S
S
Della Giulia
M
M
Pozzi
A
A
Silvani
A
A
Gaviani
P
P
Scaioli
V
V
Jandolo
B
B
Bove
L
L
Cognetti
F
F
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D012306:Risk; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D024502:alpha-Tocopherol; D002945:Cisplatin