A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients
A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients
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DOI：
10.1093/jnci/dji095
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发表时间：
2005-04-06
影响因子：
10.3
通讯作者：
Roy, J
中科院分区：
文献类型：
--
作者：
Bairati, I;Meyer, F;Roy, J
背景：虽然饮食中抗氧化剂维生素和矿物质的低摄入量与癌症的高风险有关，但抗氧化剂补充剂用于癌症化学预防的试验结果一直不明确。我们评估了补充抗氧化剂维生素是否可以降低头颈癌患者的第二原发癌的发生率。方法：我们对1994年10月1日至2000年6月6日期间接受放射治疗的540名I期或II期头颈癌患者进行了一项多中心、双盲、安慰剂对照、随机化学预防试验。补充α-生育酚(400IU/天)和β-胡萝卜素(30毫克/天)或安慰剂从放射治疗的第一天开始，并在放射治疗结束后持续3年。在试验过程中，出于伦理考虑，156名患者入选后，β-胡萝卜素补充剂停止服用。其余患者仅接受α-生育酚或安慰剂治疗。生存评估采用Kaplan-Meier分析。用COX比例风险模型估计危险比(HR)和95%可信区间(CI)。所有的统计检验都是双面的。结果：经过52个月的中位随访，113名参与者被诊断为第二原发癌，119名被诊断为第一肿瘤复发。补充剂对第二原发癌发病率的影响随着时间的推移而变化。与服用安慰剂的患者相比，补充α-生育酚的患者在补充期间第二原发癌的发生率较高(HR=2.88，95%CI=1.56~5.31)，但在补充停止后第二原发癌的发生率较低(HR=0.41，95%CI=0.16~1.03)。同样，在补充α-生育酚期间(HR=1.86，95%CI=.1.27~2.72)，复发或第二原发癌的发生率较高，而在补充α-生育酚(HR=0.71，95%CI=0.33~1.53)后，复发或第二原发癌的发生率较低。经过8年的随访，两组参与者总体上没有第二原发癌的比例是相似的。结论：补充α-生育酚对第二原发癌的发生和无癌生存有意想不到的不良影响。
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.