PHASE III TRIAL OF SELENIUM FOR PROSTATE CANCER PREVENT

本试验的主要目的是评估用必需微量元素硒（Se）治疗预防前列腺癌（PCa）的潜力。 这项试验的基本原理是基于营养预防癌症试验的结果，这是一项随机、双盲临床干预试验。这项试验的结果显示，与安慰剂组相比，在最初10年的随访中，接受200 μ g/d硒的患者的PCa发病率降低了63%。该试验将患者随机分配至安慰剂组或两种硒剂量（200 μ g/d或400 μ g/d）中的一种。该试验的主要终点是PCa的发生率和前列腺癌进展的主要血清标志物前列腺特异性抗原（PSA）的速度。 该试验的安全性终点包括硒中毒早期轻度症状的发作以及肝脏和肾脏酶水平的显著变化。 该试验将随机分配至少700名PSA水平持续升高（大于4 ng/ml）且至少一次前列腺癌活检阴性的患者。 该试验将对患者进行长达57个月的随访（平均51个月），并有80%的把握度检测到PCa发病率降低50%，α值为0.05。选择50%的治疗效果是因为它是NPC试验中观察到的治疗效果的一半，治疗滞后两年（RR=0.25）。 除了PCa发病率，前列腺活检和手术组织将进行分析，以探索前列腺癌进展的生物标志物和硒补充影响PCa的可能机制。

The principal purpose of this trial is to assess the potential for treatment with the essential trace element selenium (Se) to prevent prostate cancer (PCa). The rationale for this trial is based on the results of the Nutritional Prevention of Cancer Trial, a randomized, double-blind clinical intervention trial. The results of this trial show a 63 percent reduction in PCa incidence during the initial 10 years of follow up in the patients receiving 200 mug/d of Se compared to the placebo group1. The trial will randomize patients to either placebo or one of two Se dosages, 200 mug/d or 400 mug/d The primary endpoints for the trial are the incidence of PCa and the velocity of the primary serum marker of prostate cancer progression, prostate specific antigen (PSA). Safety endpoints for the trial include onset of early mild symptoms of Se toxicity as well as significant changes in liver and kidney enzyme levels. The trial will randomize at least 700 patients with persistently elevated PSA levels (greater than 4 ng/ml) and at least one negative biopsy for prostate cancer. The trial will follow patients for up to 57 months, (an average of 51 months) and have 80 percent power to detect a 50 percent decrease in the incidence of PCa with an alpha of 0.05. The treatment effect of 50 percent was selected because it is one half the treatment effect observed in the NPC trial after a two year treatment lag (RR=0.25). In addition to PCa incidence, prostate biopsies and surgical tissue will be analyzed to explore both biomarkers of prostate cancer progression and possible mechanisms by which Se supplementation affects PCa.