Thompson Ian M, Goodman Phyllis J, Tangen Catherine M, Lucia M Scott, Miller Gary J, Ford Leslie G, Lieber Michael M, Cespedes R Duane, Atkins James N, Lippman Scott M, Carlin Susie M, Ryan Anne, Szczepanek Connie M, Crowley John J, Coltman Charles A
University of Texas Health Science Center, San Antonio, USA.
N Engl J Med. 2003 Jul 17;349(3):215-24. doi: 10.1056/NEJMoa030660. Epub 2003 Jun 24.
Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer.
In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study.
Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo.
Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.
雄激素参与前列腺癌的发生发展。非那雄胺是一种5α-还原酶抑制剂，可抑制睾酮向双氢睾酮（前列腺中的主要雄激素）的转化，可能降低前列腺癌风险。
在前列腺癌预防试验中，我们将18882名55岁及以上、直肠指检正常且前列腺特异性抗原（PSA）水平为3.0 ng/ml或更低的男性随机分为两组，分别接受非那雄胺（每日5 mg）或安慰剂治疗，为期7年。如果经非那雄胺效应校正后的年度PSA水平超过4.0 ng/ml或直肠指检异常，则建议进行前列腺活检。预计60%的参与者在研究期间会被诊断出前列腺癌或在研究结束时接受活检。主要终点是研究7年期间前列腺癌的患病率。
在最终分析中有数据的非那雄胺组4368名男性中，803人检测出前列腺癌（18.4%）；安慰剂组4692名有此类数据的男性中，1147人检测出前列腺癌（24.4%），7年期间患病率降低了24.8%（95%置信区间为18.6%至30.6%；P<0.001）。在非那雄胺组中，Gleason分级为7、8、9或10级的肿瘤更为常见（757例肿瘤中有280例[37.0%]，占最终分析纳入的4368名男性的6.4%），而在安慰剂组中（1068例肿瘤中有237例[22.2%]，两组比较P<0.001；占最终分析纳入的4692名男性的5.1%，两组比较P=0.005）。接受非那雄胺治疗的男性出现性副作用更为常见，而接受安慰剂的男性出现泌尿系统症状更为常见。
非那雄胺可预防或延迟前列腺癌的出现，但这种潜在益处以及泌尿系统问题风险的降低必须与性副作用和高级别前列腺癌风险的增加相权衡。
