Effect of dutasteride on clinical progression of benign prostatic hyperplasia in asymptomatic men with enlarged prostate: a post hoc analysis of the REDUCE study (original) (raw)
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Effect of Dutasteride on the Risk of Prostate Cancer
New England Journal of Medicine, 2010
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.
Dutasteride significantly improves quality of life measures in patients with enlarged prostate
Prostate Cancer and Prostatic Diseases, 2008
The purpose of this study was to determine the effect of dutasteride on quality of life of men with lower urinary tract symptoms associated with enlarged prostate or benign prostatic hyperplasia (BPH) as measured by symptom problem index (SPI), BPH-specific interference with activities (BSIA), BPH-specific psychological well-being (BPWB) and BPH-specific lifestyle adaptations (BSLA). Data were derived from three randomized, double-blind studies conducted in 4325 men treated with placebo or dutasteride (0.5 mg/day). Primary analyses included changes from baseline in mean SPI, BSIA, BPWB and BSLA scores. Men treated with dutasteride showed significant improvements in SPI, BSIA, BPWB and BSLA scores compared with placebo.
Journal of Men's Health, 2009
Dutasteride has been shown to significantly improve symptoms of benign prostatic hyperplasia (BPH) and reduce clinical progression. Recent data from studies evaluating 5-alpha reductase inhibitors (5-ARIs) for the prevention of prostate cancer, however, suggest 5ARIs, including dutasteride, may be associated with increased incidence of Gleason 8-10 prostate tumours. This metaanalysis was undertaken to quantify the effect of dutasteride on detection of prostate cancer and high-grade prostate cancer. Methods: Our meta-analysis includes data from GlaxoSmithKlinesponsored phase III randomized clinical trials (with a study duration of ≥2 years) evaluating the effect of dutasteride, alone or in combination with tamsulosin, to treat BPH or to reduce the risk of prostate cancer. The incidence of prostate cancer, including Gleason 7-10 and Gleason 8-10, for patients taking either dutasteride, dutasteride plus tamsulosin, tamsulosin alone, or placebo, were evaluated using the Mantel-Haenszel Risk Ratio (MHRR) method of conducting meta-analyses.
Urology, 2009
In this study we assessed the possible influence of dutasteride (types 1 and 2 isoenzymes of 5-alpha-reductase inhibitors) on prostate tissue vascularity. We also attempted to evaluate whether preoperative treatment with dutasteride could help to avoid excessive bleeding in patients undergoing transurethral resection of prostate (TUR-P). METHODS This pilot study has 3 phases. All patients enrolled in the study had a prostate-specific antigen Ͻ 4 ng/mL and normal digital rectal examination. In the first phase we included 10 patients with benign prostatic hyperplasia treated with alpha-blockers. The end point of this phase was to choose the preset that could exclude noise signals and be reproducible. In the second phase, we included 32 patients in whom color Doppler sonography (CDS) was performed before and 6 weeks after treatment with 0.5 mg dutasteride per day. We counted every discrete color Doppler signal (CD-spot). To compare the CDS data, we used the Student t test, and P Ͻ .05 was considered significant. Afterward, 46 patients joined the third phase. Patients were assigned to the control and study groups according to sequentially numbered sealed envelopes. Patients in the study group received 0.5 mg dutasteride 6 weeks before TUR-P. RESULTS In the first phase: color Doppler preset with pulse repetition frequency of 0.3 kHz was chosen as the most sensible. In the second phase, a significant decline in CD-spots count was detected in 23 (72%) patients (P Ͻ .05) and was more distinctive in the periurethral zone. In the third phase, only 43 of the patients continued with TUR-P (in 3 patients, voiding symptoms improved). Operating time and volume of irrigation fluid were significantly different (50.55 minutes/42.65 minutes, P ϭ .014; 8.03/13.10 L, P ϭ .047). CONCLUSIONS Six weeks of dutasteride treatment may reduce prostate tissue vascularity in the periurethral area proximal to the verumontanum. The third phase of our study confirmed that preoperative treatment with dutasteride could improve operative performance and avoid TUR syndrome.
European Urology, 2004
Objectives: Dutasteride, a dual inhibitor of Type 1 and Type 2 5a-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. Methods: 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 0.5 mg daily (dutasteride/ dutasteride [D/D] group and placebo/dutasteride [P/D group]). Results: 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. Conclusions: 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 BPHrelated surgery, seen in the double-blind phase, was durable over 4-year treatment. Dutasteride was also well tolerated in long-term use. #
Update on the use of dutasteride in the management of benign prostatic hypertrophy
Clinical Interventions in Aging, 2007
Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms, with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and epithelial prostatic elements that surround the urethra cause lower urinary tract symptoms (LUTS), urinary tract infection, and acute urinary retention. Medical treatments of symptomatic BPH include; 1) the 5α-reductase inhibitors, 2) the α1-adrenergic antagonists, and 3) the combination of a 5α-reductase inhibitor and a α1-adrenergic antagonist. Selective α1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine fl ow without compromising bladder contractility. Clinical trials have shown that α1-adrenergic antagonists decrease LUTS and increase urinary fl ow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Inhibitors of 5α-reductase decrease production of dihydrotestosterone within the prostate resulting in decreased prostate volumes, increased peak urinary fl ow rates, improvement of symptoms, and decreased risk of acute urinary retention and need for surgical intervention. The combination of a 5α-reductase inhibitor and a α1-adrenergic antagonist reduces the clinical progression of BPH over either class of drug alone.
European Urology, 2010
Background: Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement. Objective: To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression over 4 yr in men at increased risk of progression. Design, setting, and participants: The Combination of Avodart 1 and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men !50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score !12, prostate volume !30 cm 3 , prostate-specific antigen 1.5-10 ng/ml, and maximum urinary flow rate (Q max ) >5 and 15 ml/s with minimum voided volume !125 ml. Intervention: Oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. Measurements: The 4-yr primary end point was time to first AUR or BPH-related surgery. Secondary end points included BPH clinical progression, symptoms, Q max , prostate volume, safety, and tolerability. Results and limitations: Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery. Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression. Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of an imbalance in the composite term of cardiac failure among the three study arms. The lack of placebo control is a study limitation. Conclusions: The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement. Clinicaltrials.gov identifier: NCT00090103
Urology, 2002
Objectives. To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II. Methods. A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm 3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments. Results. At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median Ϫ93.7%; P Ͻ0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P Ͻ0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P Ͻ0.001) and a reduction of 4.5 points (21.4%) at 24 months (P Ͻ0.001). The maximal flow rate improved significantly from 1 month (P Ͻ0.01), with an increase of 2.2 mL/s reported at 24 months (P Ͻ0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated. Conclusions. Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period. UROLOGY 60: 434-441, 2002.
The Journal of Urology, 2011
Purpose-Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. Materials and Methods-We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. Results-A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Conclusions-Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during