度他雄胺对前列腺癌风险的影响。

Effect of dutasteride on the risk of prostate cancer.

机构信息

Division of Urology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.

出版信息

N Engl J Med. 2010 Apr 1;362(13):1192-202. doi: 10.1056/NEJMoa0908127.

DOI:10.1056/NEJMoa0908127

PMID:20357281

Abstract

BACKGROUND

We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease.

METHODS

In this 4-year, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we compared dutasteride, at a dose of 0.5 mg daily, with placebo. Men were eligible for inclusion in the study if they were 50 to 75 years of age, had a prostate-specific antigen (PSA) level of 2.5 to 10.0 ng per milliliter, and had had one negative prostate biopsy (6 to 12 cores) within 6 months before enrollment. Subjects underwent a 10-core transrectal ultrasound-guided biopsy at 2 and 4 years.

RESULTS

Among 6729 men who underwent a biopsy or prostate surgery, cancer was detected in 659 of the 3305 men in the dutasteride group, as compared with 858 of the 3424 men in the placebo group, representing a relative risk reduction with dutasteride of 22.8% (95% confidence interval, 15.2 to 29.8) over the 4-year study period (P<0.001). Overall, in years 1 through 4, among the 6706 men who underwent a needle biopsy, there were 220 tumors with a Gleason score of 7 to 10 among 3299 men in the dutasteride group and 233 among 3407 men in the placebo group (P=0.81). During years 3 and 4, there were 12 tumors with a Gleason score of 8 to 10 in the dutasteride group, as compared with only 1 in the placebo group (P=0.003). Dutasteride therapy, as compared with placebo, resulted in a reduction in the rate of acute urinary retention (1.6% vs. 6.7%, a 77.3% relative reduction). The incidence of adverse events was similar to that in studies of dutasteride therapy for benign prostatic hyperplasia, except that in our study, as compared with previous studies, the relative incidence of the composite category of cardiac failure was higher in the dutasteride group than in the placebo group (0.7% [30 men] vs. 0.4% [16 men], P=0.03).

CONCLUSIONS

Over the course of the 4-year study period, dutasteride reduced the risk of incident prostate cancer detected on biopsy and improved the outcomes related to benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00056407.)

摘要

背景

我们进行了一项研究，以确定非那雄胺是否能降低患有前列腺癌风险增加的男性的前列腺癌发病率，这些男性的前列腺癌是通过活检检测到的。

方法

在这项为期 4 年的、多中心的、随机的、双盲的、安慰剂对照的平行组研究中，我们比较了非那雄胺（每天 0.5 毫克）与安慰剂的效果。只有在以下情况下，男性才有资格参加这项研究：年龄在 50 至 75 岁之间，前列腺特异性抗原（PSA）水平为每毫升 2.5 至 10.0 纳克，并且在入组前 6 个月内进行过一次阴性前列腺活检（6 至 12 个核心）。受试者在 2 年和 4 年时进行了 10 个核心经直肠超声引导活检。

结果

在 6729 名接受活检或前列腺手术的男性中，在非那雄胺组的 3305 名男性中，有 659 名男性的前列腺癌被检测到，而在安慰剂组的 3424 名男性中，有 858 名男性的前列腺癌被检测到，这意味着在 4 年的研究期间，非那雄胺组的相对风险降低了 22.8%（95%置信区间为 15.2 至 29.8）（P<0.001）。总的来说，在 1 至 4 年期间，在 6706 名接受针吸活检的男性中，在非那雄胺组的 3299 名男性中有 220 名男性的 Gleason 评分为 7 至 10 分，在安慰剂组的 3407 名男性中有 233 名男性的 Gleason 评分为 7 至 10 分（P=0.81）。在第 3 年和第 4 年期间，非那雄胺组有 12 名男性的 Gleason 评分在 8 至 10 分之间，而安慰剂组只有 1 名男性（P=0.003）。与安慰剂相比，非那雄胺治疗降低了急性尿潴留的发生率（1.6%对 6.7%，相对减少 77.3%）。不良事件的发生率与非那雄胺治疗良性前列腺增生的研究相似，除了在我们的研究中，与之前的研究相比，心力衰竭的复合类别在非那雄胺组中的相对发病率高于安慰剂组（0.7%[30 名男性]对 0.4%[16 名男性]，P=0.03）。