Studies have found an association between low dietary intake of antioxidants and an increased risk of cancer, but trials that have tested the cancer-preventive effects of antioxidant supplementation have had mixed results. Two of the most studied vitamins have been alpha-tocopherol (vitamin E) and beta-carotene, a precursor of vitamin A.
To determine whether antioxidant supplementation could reduce the risk of second primary cancers in head and neck cancer patients, Isabelle Bairati, M.D., Ph.D., of the Université Laval in Québec City, Québec, and colleagues conducted a multicenter, double-blind, placebo-controlled, randomized trial among 540 patients with stage I or II head and neck cancer who had been treated with radiation therapy between 1994 and 2000. Participants received supplementation with alpha-tocopherol and beta-carotene or a placebo during radiation therapy and for the next 3 years. (Beta-carotene supplementation was discontinued about 1 year into the trial because results from a different large trial found an increased incidence of lung cancer among smokers receiving beta-carotene.) Participants were followed for a median of 52 months.
Compared with patients given a placebo, patients who received alpha-tocopherol supplements had a higher rate of developing a second primary cancer during the period of supplementation but a lower risk of a second primary cancer after supplementation ended. Overall, the proportion of participants free of a second primary cancer after 8 years of follow-up was similar in both groups of patients. The rate of having a recurrence of the head and neck cancer or a second primary cancer was also higher during supplementation among patients receiving alpha-tocopherol than among patients receiving placebo but lower after supplementation had ended.
"This cancer chemoprevention trial was conducted in a population of patients at high risk of second primary cancers. There is some concern about the generalization of the study results to individuals in the general population who are at low risk of a first primary cancer. Nevertheless, our results suggest that caution should be advised regarding the use of high-dose alpha-tocopherol supplements for cancer prevention," the authors write.
In an editorial, Edward S. Kim, M.D., and Waun Ki Hong, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston, review the current state of the use of antioxidants for cancer chemoprevention. "The field of chemoprevention still remains an exciting area of research, yet many challenges are ahead," they write. "Risk stratification factors must become more specific and scientific. This, in turn, will allow us to treat the patient in a more biomarker-integrated approach. Only then will we be able to discover that elusive 'golden apple' of chemoprevention."
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JNCI Journal of the National Cancer Institute