Adult urologyEfficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia☆
Section snippets
Material and methods
At the time of writing, the data from the two U.S. studies, ARIA3001 and ARIA3002, were available. These were 2-year, double-blind, randomized, placebo-controlled trials with an additional 2-year open-label phase. During the open-label portion of the study, subjects initially receiving dutasteride continued to take dutasteride (dutasteride/dutasteride group), and those initially receiving placebo began to take open-label dutasteride (placebo/dutasteride group). The design of the double-blind
Patient demographics
A total of 2802 men were randomized into the double-blind phase of the two studies; 1908 (68%) completed the 2-year double-blind phase. In the open-label phase of the study, 1570 subjects were enrolled; 778 had previously received placebo and 792 had previously received dutasteride for the 2-year double-blind phase (Fig. 1). Overall, 569 subjects received dutasteride for 48 months. Table I includes the data for subjects in the double-blind and open-label ITT populations.
Changes in the
Comment
Inhibition of 5-α-reductase reduces symptoms of BPH and lowers the risk of long-term disease-related sequelae.4, 5, 6 Dutasteride, which inhibits both type 1 and type 2 isoenzymes of 5-α-reductase, reduces circulating DHT by more than 90% and has been shown to be safe and efficacious in three large-scale, 2-year Phase IIIa studies.4 Two of these studies, in which subjects completed an additional 24-month open-label phase, provide 4 years of data supporting the continued effectiveness and
Conclusions
Dual inhibition of the type 1 and type 2 5-α-reductase isoenzymes with dutasteride provided sustained and durable efficacy in symptomatic BPH subjects treated for 48 months, with clinically relevant improvements in prostate volume, AUA-SI, and Qmax. Symptom and flow rate improvements at 48 months in the dutasteride/dutasteride-treated patients were comparable to those seen with alpha-receptor blocking agents. The incidence of AUR and the need for BPH-related surgery was low. The low incidence
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2017, DifferentiationCitation Excerpt :The fact that needle biopsies have proven ineffective for the histological diagnosis of BPH (Viglione et al., 2002) and therefore excluded from standard clinical practice has prohibited the study of pathologic progression in an individual patient. The only source of longitudinal tissue samples from individual patients comes from a few clinical trials where biopsies were performed at the beginning and end of the trial, but these tissues are not readily available (McConnell et al., 2003b; Roehrborn et al., 2004). Accordingly, a mechanistic understanding and experimental testing of potentially pathogenic molecular factors driving benign growth or therapeutic resistance has only been studied by a prospective grouping of cohorts by either indication of surgery (e.g. ‘control’ transition zone from age-matched prostate or bladder cancer patients vs. transition zone from BPH/LUTS patients (Bauman et al., 2014; Lin-Tsai et al., 2014; Ma et al., 2012)), or indication of severity (e.g., prostate volume (Descazeaud et al., 2008), SRD5A2 expression (Bechis et al., 2015), etc.).
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2016, Journal of Sexual MedicineCitation Excerpt :Fifty articles were excluded because they were not relevant or did not fulfill the inclusion criteria. After full-text reviews of 23 potentially relevant studies, four studies17,44–46 were found to have used the same study population, three studies4,19,20 were from the same clinical trial (PLESS), and the other two studies18,47 concerned the same large-scale, randomized, placebo-controlled, phase III studies. Among these, only the original studies were used.4,17,18
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2016, Urologic Clinics of North America
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This study was funded by GlaxoSmithKline.
C. G. Roehrborn is a study investigator funded by GlaxoSmithKline and Merck; L. S. Marks is a study investigator funded by GlaxoSmithKline, Merck, Sanofi Synthelabo, Beckman Coulter, and Lilly; T. Fenter, S. Freedman, and J. Tuttle are study investigators funded by GlaxoSmithKline; and M. Gittelman is a study investigator funded by GlaxoSmithKline, Merck, and Sanofi Synthelabo.