A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients.
What this study found
The supplementation strategy did not improve cancer outcomes and was associated with worse cancer-free outcomes during the supplementation period. For second primary cancers in the first 3.5 years, hazard ratios were 2.42 (1.45 to 4.04) for any supplementation and 2.88 (1.56 to 5.31) for α-tocopherol alone; beyond 3.5 years, the estimates were 0.57 (0.31 to 1.07) and 0.41 (0.16 to 1.03), respectively. Cancer-free survival was also worse during supplementation, with HR 1.65 (1.21 to 2.25) for any supplementation and 1.86 (1.27 to 2.72) for α-tocopherol alone. The authors concluded that…
- Study & population
- Randomized, multicenter trial in adults 18 years or older with stage I or II head and neck squamous cell carcinoma receiving radiation therapy in Quebec, Canada.
- Intervention
- Oral dl-α-tocopherol 400 IU daily was given during radiation therapy and continued for 3 years afterward.
- Key limitation
- Interpretation is limited by the trial population being restricted to early-stage head and neck cancer patients treated with radiation therapy, which limits generalizability.
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Open PDFOriginal abstract
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 alpha-tocopherol (400 IU/day) and beta-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, beta-carotene supplementation was discontinued after 156 patients had enrolled because of ethical concerns. The remaining patients received alpha-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 alpha-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 alpha-tocopherol. The proportion of participants free of second primary cancer overall after 8 years of follow-up was similar in both arms. CONCLUSIONS alpha-Tocopherol supplementation produced unexpected adverse effects on the occurrence of second primary cancers and on cancer-free survival.