© 2005 Oxford University Press
ARTICLE |
A Randomized Trial of Antioxidant Vitamins to Prevent Second Primary Cancers in Head and Neck Cancer Patients
Affiliations of authors: Centre de Recherche en Cancérologie de L'Université Laval (IB, FM, BT, FH) and the Centre Hospitalier Universitaire de Québec (AF, EV, JR), Québec City, Québec, Canada; the Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada (MG, PDV); the Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada (AN); the Complexe Hospitalier de la Sagamie, Saguenay, Québec, Canada (FB, SV); the Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada (J-PM); the Fred Hutchinson Cancer Research Center, Seattle, WA (BM)
Correspondence to: François Meyer, MD, DSc, Centre de Recherche en Cancérologie, Université Laval, 11 côte du Palais, Québec, Québec G1R 2J6, Canada (e-mail: francois.meyer{at}chuq.qc.ca).
Background: Although low dietary intakes of antioxidant vitamins and minerals have been associated with higher risks of cancer, results of trials testing antioxidant supplementation for cancer chemoprevention have been equivocal. We assessed whether supplementation with antioxidant vitamins could reduce the incidence of second primary cancers among patients with head and neck cancer. Methods: We conducted a multicenter, double-blind, placebo-controlled, randomized chemoprevention trial among 540 patients with stage I or II head and neck cancer treated by radiation therapy between October 1, 1994, and June 6, 2000. Supplementation with 
-tocopherol (400 IU/day) and 
-carotene (30 mg/day) or placebo began on the first day of radiation therapy and continued for 3 years after the end of radiation therapy. In the course of the trial, -carotene supplementation was discontinued after 156 patients had enrolled because of ethical concerns. The remaining patients received -tocopherol or placebo only. Survival was evaluated by Kaplan-Meier analysis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: After a median follow-up of 52 months, second primary cancers and recurrences of the first tumor were diagnosed in 113 and 119 participants, respectively. The effect of supplementation on the incidence of second primary cancers varied over time. Compared with patients receiving placebo, patients receiving -tocopherol supplements had a higher rate of second primary cancers during the supplementation period (HR = 2.88, 95% CI = 1.56 to 5.31) but a lower rate after supplementation was discontinued (HR = 0.41, 95% CI = 0.16 to 1.03). Similarly, the rate of having a recurrence or second primary cancer was higher during (HR = 1.86, 95% CI = 1.27 to 2.72) but lower after (HR = 0.71, 95% CI = 0.33 to 1.53) supplementation with -tocopherol. The proportion of participants free of second primary cancer overall after 8 years of follow-up was similar in both arms. Conclusions: -Tocopherol supplementation produced unexpected adverse effects on the occurrence of second primary cancers and on cancer-free survival.
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Editorial about this Article
- An Apple a Day...Does It Really Keep the Doctor Away? The Current State of Cancer Chemoprevention
- Edward S. Kim and Waun Ki Hong
J Natl Cancer Inst 2005 97: 468-470.[Extract] [Full Text] [PDF]
Related Memo to the Media
- Press Release: Antioxidant May Have Adverse Effects in Head and Neck Cancer Patients
- Sarah L. Zielinski
J Natl Cancer Inst 2005 97: 467.[Extract] [Full Text]
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