March 21, 2014

Vitamin E Protects Patients from Cisplatin-induced Neuropathy in a Randomized Trial

Cisplatin use is limited by severe neurotoxicity. When the cumulative dose exceeds 300 mg/m2, in some reports most patients suffer significant neurological damage. Cisplatin is known to increase oxidative stress; vitamin E is an antioxidant, and current evidence suggests that the antioxidant actions of vitamin E do not interfere with the therapeutic effect of chemotherapy.

Reference

Pace A, Giannarelli D, Galie E, et al. Vitamin E neuroprotection for cisplatin neuropathy. Neurology. 2010;74:762-766.

Design

Randomized, double-blind intervention trial

Participants

Of 108 patients initially randomized in the trial, 41 were treated with cisplatin exceeding 300 mg/m2. Of these 41 subjects, 17 had been given vitamin E and 24 had been given placebo.

Study Medication and Dosage

596 IU d-alpha tocopherol or placebo daily, begun 1 to 8 days before the start of cisplatin therapy and continued for 3 months following discontinuation of cisplatin therapy

Outcome Measures

Development of peripheral neuropathy as a result of cisplatin therapy and measurement of the severity of the neurological damage through the use of total neuropathy score (TNS)

Key Findings

Neurotoxicity occurred in 6% in the vitamin E group versus 42% in the placebo group (P<0.01). The severity of neurological damage was also far lower in the vitamin E group (1.4 TNS vs. 4.1; P<0.01).

Practice Implications

Cisplatin use is limited by severe neurotoxicity. When the cumulative dose exceeds 300 mg/m2, in some reports most patients suffer significant neurological damage. Cisplatin is known to increase oxidative stress; vitamin E is an antioxidant, and current evidence suggests that the antioxidant actions of vitamin E do not interfere with the therapeutic effect of chemotherapy.1 Neuropathy has been reported to occur as part of the presentation of vitamin E deficiency. As a result, researchers are interested in exploring the ability of vitamin E to protect against cisplatin-induced neuropathies.

Researchers are interested in exploring the ability of vitamin E to protect against cisplatin-induced neuropathies.

In 2007, a Cochrane review concluded that previous evidence linking the use of vitamin E to protection against neuropathy in patients given cisplatin was encouraging but needed additional support from randomized clinical trials.2 The findings of the new trial take us a significant step in that direction. Until more is known, all patients given cisplatin should concomitantly take vitamin E supplements beginning several days before the start of the chemotherapy.

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References

1. Leonetti C, Biroccio A, Gabellini C, et al. Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy. Int J Cancer. 2003;104(2):243-250.

2. Albers J, Chaudhry V, Cavaletti G, Donehower R. Interventions for preventing neuropathy caused by cisplatin and related compounds. Cochrane Database Syst Rev. 2007;(1):CD005228.