Protective Effect Of Vitamin E (VE ) In Head And Neck Cancer Radiation Induced Mucositis: A Double-Blind Randomized Trial

Reviewer: Roberto Santiago, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 22, 2002

Presenter: Paulo R Ferreira
Presenter's Affiliation: Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
Type of Session: Scientific

Background

Vitamin E is the most important antioxidant in the human body
It scavenges free radicals and prevents lipid membrane peroxidation
Vitamin E has been proposed as a potential radioprotectant agent
A few small studies have suggested that vitamin E can significantly reduce the incidence of oral mucositis observed during the treatment of cancer patients (Osaki et al, Lopez et al, and Wadleigh et al)
Patients with cancer of the head and neck treated with radiotherapy are at especially high risk for developing oral mucositis
The resulting pain and dysphagia can be severe, leading to malnutrition, infection, medical interventions, and reliance on narcotic analgesics
Oxygen free radicals and their effects on microvasculature has been postulated to play a role in the pathogenesis of radiotherapy-related oral mucositis
No effective prevention for mucositis exists to date

Materials and Methods

A prospective double-blind randomized trial was design to evaluate the protective effectiveness of vitamin E against oral mucositis in patients with squamous cell carcinomas of the oral cavity and oropharynx treated with radiation therapy alone
Patient and tumor characteristics, including alcohol intake and smoking, were well balanced among the treatment arm
Only Pre- or postoperative radiotherapy conventionally fractionated was used
Experimental treatments consisted of twice-daily 5-minute oral cavity rinse (and swallow) just before radiotherapy and 12 hours later every day using either vitamin E (400 mg oil solution) or placebo (500 mg capsules of primrose oil)
Radiation doses ranged from 50?70 Gy delivered in 2 Gy fractions 5 days a week using parallel opposed fields with Cobalt units (minimum area of 12.2 square centimeters)
The patient?s oral cavities in both arms were clinically inspected once a week and mucositis was evaluated the 4-tier RTOG toxicity scale
Patients were given a simple non-validated questionnaire to assess quality of life similar to that used in comparable studies
Mucosal cells were collected weekly for micronuclei assay (cellular surrogate for radiation damage)
The density of incidence of severe mucositis was evaluated in both arms (# of mucositis events > grade 2 ¸ # ?patient-weeks? of exposure)
The duration of mucositis and the patient?s weights were also assessed

Results

Patients in the placebo group had severe mucositis more frequently than those in the vitamin E group (54 events / 161 patients-week = 33.5% versus 36 events / 167 patients-week = 21.6%, p=0.038)
Vitamin E afforded a 36% reduction in the risk of severe mucositis
Pain was worst in the placebo group
There was no significant difference in the duration of mucositis or on weight loss experienced by the patients in the two arms
No adverse effects were attributable to the experimental treatment in either arm

Author's Conclusions

Vitamin E is very well tolerated in patients undergoing radiotherapy for cancer of the head and neck
Vitamin E afforded a reduction in the incidence of severe radiation-induced mucositis in patients treated for cancer of the head and neck

Clinical/Scientific Implications

The study was limited by the collection of one assessment per week in a small number of patients
The density of incidence method conceals this limitation
They used a quality of life tool that was not validated
The survival in the treatment arms did not differ significantly
The findings of this study should prompt larger carefully designed trials to further investigate the potential benefit afforded by vitamin E
Long-term follow-up will be needed to assess local control and survival as there is a theoretical tumor protection possibility with vitamin E utilization

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