Afonseca, S.O., Cruz, F.M., Cubero Dde, I., Lera, A.T., Schindler, F., Okawara, M., . . . Giglio, A. (2013). Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: A pilot randomized clinical trial. Sao Paulo Medical Journal, 131, 35–38.

To evaluate if oral daily vitamin E is an effective agent in preventing oxaliplatin-induced peripheral neuropathy

Patients were randomized to receive either an oral placebo daily or 400 mg of oral vitamin E daily starting five days before their oxaliplatin-based regimen and continued until completion of the oxaliplatin-based regimen. Both groups received calcium 1 gram IV and magnesium 1 gram IV supplementation 30 minutes before and the same dose after the completion of 12 cycles of oxaliplatin infusions.

• N = 32 (18 in the vitamin E group, 16 in the placebo group)  
• MEAN AGE = 56 years in the vitamin E group; 57 years in the placebo group
• MALES: 10 in the vitamin E group, 8 in the placebo group; FEMALES: 8 in the vitamin E group, 8 in the placebo group
• KEY DISEASE CHARACTERISTICS: Equal distribution of colon cancer, rectal cancer, and advanced gastric cancer; metastatic colon cancer: three in the vitamin E group, zero in the placebo group
• OTHER KEY SAMPLE CHARACTERISTICS: Eastern Cooperative Oncology Group score 0–1: equal distribution; FOLFOX, FLOX, and EOX regimens: equal distribution; diabetes: two patients in the vitamin E group, zero in the placebo group; previous chemotherapy, radiotherapy, and ETOH consumption: equal distribution
• EXCLUSION CRITERIA: Patients with previous history of peripheral neuropathy or symptoms of peripheral neuropathy; patients receiving gabapentin, carbamazepine, amitriptyline, amifostine, or multivitamins

• SITE: Department of hematology and oncology
• SETTING TYPE: University hospital  
• LOCATION: Santo Andre, Sao Paulo, Brazil

• PHASE OF CARE: Adjuvant, advanced, and metastatic
• APPLICATIONS: Elder care, palliative care

• Prospective, phase II, randomized, double-blind pilot study

• Common Terminology Criteria for Adverse Events (version 3) and gradation scales for oxaliplatin based on National Cancer Institute Common Toxicity Criteria in the assessment of chemotherapy-induced peripheral neuropathy to detect a 50% decrease in the incidence of peripheral neuropathy with a power of 0.8 and a type I error of 0.05

In evaluating the effectiveness of oral vitamin E 400 mg daily for prevention of oxaliplatin-induced peripheral neuropathy, this study sought to detect a 50% reduction in associated peripheral neuropathy. The results showed no significant decrease in the incidence of acute oxaliplatin-induced peripheral neuropathy comparing vitamin E and placebo groups (p = 0.43) and no significant difference in the grade (p = 0.45) or time to onset of peripheral neuropathy (p = 0.66) between groups. Incidence of vomiting, nausea, mucositis, fatigue, headache, vertigo, and bleeding observed between groups showed no statistical difference. Incidence of diarrhea was increased in the vitamin E group (p = 0.06).

There is no difference in the incidence, grade, or time to onset of peripheral neuropathy when comparing vitamin E given at 400 mg orally daily or placebo in patients receiving 12 cycles of an oxaliplatin-based regimen (i.e., FOLFOX, FLOX, EOX).

• Small sample (less than 100)
• Measurement/methods were not well described. All time points for evaluation of peripheral neuropathy were not clearly stated. Any dose adjustment for the chemotherapy regimen or oxaliplatin dose, treatment delay, or missed treatment were not mentioned or addressed.
• Other limitations/explanation: Both groups received calcium and magnesium supplementation that may have confounded results. The clinical effectiveness of vitamin E may not have been measured adequately. Dosing of vitamin E at 400 mg daily was based on only one previous clinical trial using cisplatin, not oxaliplatin. There may have been differences in peripheral neuropathy under the 50% measurement used that were not able to be evaluated.

This small pilot study showed no benefit of vitamin E in preventing or reducing the onset or grade of peripheral neuropathy with oxaliplatin-based regimens over 12 weeks. Patients receiving vitamin E had increased signs and symptoms of diarrhea. Further nursing research is needed to evaluate the therapeutic value of vitamin E in this setting.