Debruyne Frans, Barkin Jack, van Erps Peter, Reis Mario, Tammela Teuvo L J, Roehrborn Claus
426 Department of Urology, University Hospital Nijmegen, Geert Grooteplein 10, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Eur Urol. 2004 Oct;46(4):488-94; discussion 495. doi: 10.1016/j.eururo.2004.05.008.
Dutasteride, a dual inhibitor of Type 1 and Type 2 5 alpha-reductase, has been shown to improve disease measures in patients with symptomatic benign prostatic hyperplasia (BPH) in three randomised, placebo-controlled, large-scale, 2-year Phase III clinical studies. This paper reports the pooled results of a 2-year open-label extension of the three randomised studies assessing the long-term efficacy and safety of dutasteride.
Patients randomised to dutasteride or placebo in the double-blind portion of the Phase III studies were eligible for a 2-year open-label extension, where all patients received dutasteride 0.5mg daily (dutasteride/dutasteride [D/D] group and placebo/dutasteride [P/D group]).
Significant improvements in AUA-SI score and Q(max) were observed from Month 24 to 48 in both study groups. At Month 48, patients in the D/D group had significantly greater improvements in AUA-SI score and Q(max), and significantly greater reductions in prostate volume, than those in the P/D group. Acute urinary retention and BPH-related surgery occurred in a small percentage of patients during the open-label phase. No new safety issues were noted with long-term therapy. Onset of new drug-related adverse events were reported most frequently at the start of therapy and declined over time in patients receiving dutasteride.
Long-term treatment with dutasteride results in continuing improvements in urinary symptoms and flow rate, and further reductions in TPV, in men with symptomatic BPH. The reduction in risk of AUR and BPH-related surgery, seen in the double-blind phase, was durable over 4-year treatment. Dutasteride was also well tolerated in long-term use.
度他雄胺是一种1型和2型5α-还原酶的双重抑制剂,在三项随机、安慰剂对照、大规模、为期2年的III期临床研究中已显示可改善有症状良性前列腺增生(BPH)患者的疾病指标。本文报告了这三项随机研究的2年开放标签延长期的汇总结果,以评估度他雄胺的长期疗效和安全性。
在III期研究双盲阶段随机分配至度他雄胺或安慰剂组的患者符合进入2年开放标签延长期的条件,在此期间所有患者每日接受0.5mg度他雄胺(度他雄胺/度他雄胺 [D/D] 组和安慰剂/度他雄胺 [P/D] 组)。
在两个研究组中,从第24个月到第48个月观察到美国泌尿外科学会症状指数(AUA-SI)评分和最大尿流率(Qmax)有显著改善。在第48个月时,D/D组患者的AUA-SI评分和Qmax改善程度显著大于P/D组,前列腺体积缩小程度也显著大于P/D组。在开放标签阶段,一小部分患者发生了急性尿潴留和与BPH相关的手术。长期治疗未发现新的安全问题。接受度他雄胺治疗的患者中,与新药相关的不良事件最常发生在治疗开始时,并随时间减少。
对于有症状的BPH男性患者,长期使用度他雄胺可使尿路症状和尿流率持续改善,前列腺总体积进一步缩小。在双盲阶段观察到的急性尿潴留和与BPH相关手术风险降低在4年治疗期间持续存在。度他雄胺长期使用耐受性也良好。