Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.
Lancet. 2012 Mar 24;379(9821):1103-11. doi: 10.1016/S0140-6736(11)61619-X. Epub 2012 Jan 24.
We aimed to investigate the safety and efficacy of dutasteride, a 5α-reductase inhibitor, on prostate cancer progression in men with low-risk disease who chose to be followed up with active surveillance.
In our 3 year, randomised, double-blind, placebo-controlled study, undertaken at 65 academic medical centres or outpatient clinics in North America, we enrolled men aged 48-82 years who had low-volume, Gleason score 5-6 prostate cancer and had chosen to be followed up with active surveillance. We randomly allocated participants in a one-to-one ratio, stratified by site and in block sizes of four, to receive once-daily dutasteride 0·5 mg or matching placebo. Participants were followed up for 3 years, with 12-core prostate biopsy samples obtained after 18 months and 3 years. The primary endpoint was time to prostate cancer progression, defined as the number of days between the start of study treatment and the earlier of either pathological progression (in patients with ≥1 biopsy assessment after baseline) or therapeutic progression (start of medical therapy). This trial is registered with ClinicalTrials.gov, number NCT00363311.
Between Aug 10, 2006, and March 26, 2007, we randomly allocated 302 participants, of whom 289 (96%) had at least one biopsy procedure after baseline and were included in the primary analysis. By 3 years, 54 (38%) of 144 men in the dutasteride group and 70 (48%) of 145 controls had prostate cancer progression (pathological or therapeutic; hazard ratio 0·62, 95% CI 0·43-0·89; p=0·009). Incidence of adverse events was much the same between treatment groups. 35 (24%) men in the dutasteride group and 23 (15%) controls had sexual adverse events or breast enlargement or tenderness. Eight (5%) men in the dutasteride group and seven (5%) controls had cardiovascular adverse events, but there were no prostate cancer-related deaths or instances of metastatic disease.
Dutasteride could provide a beneficial adjunct to active surveillance for men with low-risk prostate cancer.
GlaxoSmithKline.
我们旨在研究 5α-还原酶抑制剂非那雄胺在选择主动监测的低危疾病男性前列腺癌进展中的安全性和疗效。
在我们的 3 年、随机、双盲、安慰剂对照研究中，我们在北美 65 个学术医疗中心或门诊诊所招募了年龄在 48-82 岁之间的男性，他们患有低体积、Gleason 评分 5-6 的前列腺癌，并选择主动监测。我们按照一比一的比例随机分配参与者，按地点分层，按四的块大小分层，接受每天一次的非那雄胺 0.5 毫克或匹配的安慰剂。参与者随访 3 年，在基线后 18 个月和 3 年后获得 12 芯前列腺活检样本。主要终点是前列腺癌进展的时间，定义为从研究治疗开始到以下较早时间的天数：病理进展（在基线后有≥1 次活检评估的患者中）或治疗进展（开始医学治疗）。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00363311。
在 2006 年 8 月 10 日至 2007 年 3 月 26 日期间，我们随机分配了 302 名参与者，其中 289 名（96%）在基线后至少进行了一次活检，被纳入主要分析。到 3 年时，144 名非那雄胺组男性中有 54 名（38%）和 145 名对照组中有 70 名（48%）发生了前列腺癌进展（病理或治疗；风险比 0.62，95%CI 0.43-0.89；p=0.009）。治疗组之间的不良事件发生率大致相同。非那雄胺组 35 名（24%）男性和对照组 23 名（15%）男性出现性不良反应或乳房增大或触痛。非那雄胺组 8 名（5%）男性和对照组 7 名（5%）男性出现心血管不良事件，但无前列腺癌相关死亡或转移性疾病。
非那雄胺可能为低危前列腺癌患者的主动监测提供有益的辅助手段。
葛兰素史克。
