Dutasteride

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Claus G Roehrborn - One of the best experts on this subject based on the ideXlab platform.

  • Rates of prostate surgery and acute urinary retention for benign prostatic hyperplasia in men treated with Dutasteride or finasteride.
    BMC urology, 2016
    Co-Authors: Josephina G. Kuiper, Claus G Roehrborn, Irene D. Bezemer, Maurice Driessen, Averyan Vasylyev, Fernie J. A. Penning-van Beest, Ron M. C. Herings
    Abstract:

    Previous studies have suggested a greater benefit for various outcomes in men diagnosed with benign prostatic hyperplasia (BPH) who are treated with Dutasteride than for men treated with finasteride. This study investigates whether the rates of BPH-related prostate surgery and acute urinary retention (AUR) differ between Dutasteride and finasteride users in the Netherlands. From the PHARMO Database Network, men aged ≥50 years with a dispensing of Dutasteride or finasteride with or without concomitant alpha-blocker treatment between March 1, 2003 and December 31, 2011 were selected. The incidence of BPH-related prostate surgery and AUR was determined during Dutasteride or finasteride treatment and stratified by type of initial BPH-treatment (5-ARI monotherapy or combination with alpha-blocker) and prescriber (general practitioner (GP) or urologist). Comparison of the incidence of BPH-related prostate surgery and AUR between the treatment groups was done by Cox proportional hazard regression. 11,822 Dutasteride users and 5,781 finasteride users were identified. Most users started treatment in combination with an alpha-blocker. Overall, Dutasteride users had a lower risk of BPH-related prostate surgery was lower among Dutasteride users than finasteride users (HR: 0.75; 95 % CI: 0.56–0.99). This lower risk among Dutasteride users was also seen when stratifying by monotherapy or combination therapy (HR: 0.73; 95 % CI: 0.54–0.98 for monotherapy and HR: 0.85; 95 % CI: 0.74–0.97 for combination therapy). However, the association was only present among men treated by urologists. For AUR the rates were low and no statistical significant difference was observed between Dutasteride and finasteride users. The risk of undergoing BPH-related prostate surgery was lower among men using Dutasteride compared to men using finasteride. The association was observed for monotherapy as well as combination therapy, however, only among men who received their prescription from a urologist.

  • influence of baseline variables on changes in international prostate symptom score after combined therapy with Dutasteride plus tamsulosin or either monotherapy in patients with benign prostatic hyperplasia and lower urinary tract symptoms 4 year res
    BJUI, 2014
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Jack Barkin, Mark Emberton, Andrea Tubaro, Betsy Brotherton, Ramiro Castro
    Abstract:

    Objective To examine, using post hoc analysis, the influence of baseline variables on changes in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax) and IPSS quality of life (QoL) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with either the α-blocker tamsulosin or the dual 5-alpha reductase inhibitor Dutasteride, alone or in combination, as part of the 4-year Combination of Avodart and Tamsulosin (CombAT) study. Patients and Methods CombAT was a 4-year, multicentre, randomized, double-blind, parallel-group study in 4844 men ≥50 years of age with a clinical diagnosis of BPH by medical history and physical examination, an IPSS ≥12 points, prostate volume (PV) ≥30 mL, total serum PSA level ≥1.5 ng/mL, and Qmax >5 mL/s and ≤15 mL/s with a minimum voided volume ≥125 mL. Eligible subjects were randomized to receive oral daily tamsulosin, 0.4 mg; Dutasteride, 0.5 mg; or a combination of both. Baseline variable subgroups analysed were as follows: PV (30 to <40; 40 to <60; 60 to <80; ≥80 mL), PSA level (1.5 to <2.5; 2.5 to <4; ≥4 ng/mL), age (median: <66, ≥66 years), IPSS (median: <16, ≥16; IPSS thresholds, <20, ≥20), IPSS QoL score (question 8, Q8) (median: <4, ≥4), Qmax (median: <10.4, ≥10.4 mL/s), BPH impact index (BII) (median: <5, ≥5) and body mass index (BMI, median: <26.8, ≥26.8 kg/m2). Within each baseline variable subgroup, changes in IPSS, Qmax and IPSS QoL Q8 from baseline were evaluated using a generalized linear model with effects for baseline IPSS, Qmax or IPSS QoL Q8 and treatment group at each post-baseline assessment up to and including the month 48 visit using a last observation carried forward approach. The treatment comparisons of combination therapy vs Dutasteride and combination therapy vs tamsulosin were performed from the general linear model with statistical significance defined as P ≤ 0.01. Results Combination therapy resulted in a significantly greater improvement from baseline IPSS at 48 months vs tamsulosin monotherapy across all baseline subgroups. The benefit of combination therapy over Dutasteride was confined to groups with lower baseline PV (<60 mL) and PSA (<4 ng/mL). In groups with baseline PV ≥60 mL and PSA ≥4 ng/mL, Dutasteride and combination therapy show similar improvements in symptoms. Combination therapy resulted in significantly improved Qmax compared with tamsulosin but not Dutasteride monotherapy. Qmax improvement appeared to increase with PV and PSA level in combination therapy subjects. The proportion of subjects with an IPSS QoL ≤2 (at least mostly satisfied) at 48 months was significantly higher with combination therapy than with Dutasteride for subgroups with PV 40–60 mL and PSA level <4 ng/mL and than with tamsulosin for all PSA subgroups and PV subgroups ≥40 mL. Conclusions CombAT data support the use of long-term combination therapy with Dutasteride and tamsulosin in patients considered at risk for progression of BPH, as determined by high PV (≥30 mL) and high PSA (≥1.5 ng/mL). Combination therapy, Dutasteride monotherapy and tamsulosin monotherapy all improved Qmax, but to different extents (combination therapy > Dutasteride >> tamsulosin), suggesting that Dutasteride contributes most to the Qmax benefit in combination therapy. Combination therapy provided consistent improvement over tamsulosin in LUTS across all analysed baseline variables at 48 months. Compared with Dutasteride, the superiority of combination therapy at 48 months was shown in patients with PV <60 mL or PSA <4 ng/mL.

  • Dutasteride improves outcomes of benign prostatic hyperplasia when evaluated for prostate cancer risk reduction: secondary analysis of the REduction by Dutasteride of prostate Cancer Events (REDUCE) trial.
    Urology, 2011
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Gerald L Andriole, J. Curtis Nickel, R. Paul Gagnier, Libby Black, Roger S Rittmaster
    Abstract:

    Objective To investigate the effect of Dutasteride versus placebo on the symptoms and associated complications of male lower urinary tract symptoms and benign prostatic hyperplasia (BPH) across a range of prostate volumes and BPH symptoms in men evaluated for prostate cancer risk reduction in the 4-year REduction by Dutasteride of prostate Cancer Events (REDUCE) trial. Methods REDUCE was a multicenter, randomized, double-blind, placebo-controlled study of prostate cancer risk reduction with daily Dutasteride 0.5 mg or placebo. Eligible men were aged 50-75 years, with a prostate-specific antigen level of 2.5-10 ng/mL and a prostate volume of ≤80 cm 3 . The prespecified and post hoc analyses were performed on the incidence of acute urinary retention, BPH-related surgery, and urinary tract infections, as well as on changes in prostate volume, International Prostate Symptom Score, BPH Impact Index, and maximal urinary flow rate (Qmax). Results A total of 8122 men were included in the efficacy population. During the 4-year study, the International Prostate Symptom Score increased in placebo-treated patients, while Dutasteride-treated patients had a stabilized or decreased International Prostate Symptom Score and improved BPH Impact Index and quality of life due to urinary symptom scores across all prostate volume quintiles (including prostate glands smaller than those studied in previous Dutasteride trials). 48 months, the incidence of acute urinary retention or BPH-related surgery was significantly less in the Dutasteride group (2.5%) than in the placebo group (9%) overall ( P P Conclusion During the 4-year study, Dutasteride was associated with a decreased risk of BPH progression in men with mild-to-moderate symptoms and normal or enlarged prostates.

  • the effects of Dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms luts and benign prostatic hyperplasia bph 4 year data from the combination of avodart and tamsulosin combat stu
    BJUI, 2011
    Co-Authors: Francesco Montorsi, Claus G Roehrborn, Javier Garciapenit, Michael Borre, Ton A Roeleveld, Jean Charles Alimi, Paul Gagnier, Timothy Wilson
    Abstract:

    Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Long-term treatment with combination therapy (Dutasteride plus tamsulosin) is significantly superior to tamsulosin but not Dutasteride at reducing the relative risk of AUR or BPH-related surgery. Furthermore, combination therapy is significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression, and provides significantly greater reductions in IPSS. In addition, combination therapy significantly improves patient-reported, disease specific QoL and treatment satisfaction compared with either monotherapy. Two-year results from the CombAT study showed that combination therapy was more effective than either monotherapy in controlling both storage and voiding symptoms, irrespective of baseline prostate volume (for men with prostate volume ≥30 cc). This post-hoc two-year analysis also showed that treatment with Dutasteride not only improved voiding symptoms, as would be expected from its effects on prostate volume, but was also as effective as the α-blocker tamsulosin in the control of storage symptoms. OBJECTIVE •  To assess the effects of combined therapy with Dutasteride and tamsulosin on voiding and storage symptoms compared with those of Dutasteride or tamsulosin alone, using 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. PATIENTS AND METHODS •  Men (n = 4844) aged ≥50 years with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH), a prostate volume of ≥30 mL, and a serum prostate-specific antigen level of 1.5–10 ng/mL. •  CombAT was a multicentre, double-blind, parallel-group study. •  Oral Dutasteride (0.5 mg) or tamsulosin (0.4 mg) alone or in combination was taken daily for 4 years. •  Mean changes from baseline in storage and voiding symptoms at 4 years were assessed using subscales of the International Prostate Symptom Score. RESULTS •  At 4 years, the mean reduction in the storage subscore was significantly greater in the combined therapy group vs the Dutasteride (adjusted mean difference −0.43) and tamsulosin (adjusted mean difference −0.96) monotherapy groups (P < 0.001). •  Also at 4 years, the mean reduction in the voiding subscore was significantly greater in the combined therapy group vs the Dutasteride (adjusted mean difference −0.51) and tamsulosin (adjusted mean difference −1.60) monotherapy groups (P < 0.001). •  The improvement in the storage subscore with combined therapy was significantly better (P < 0.001) than Dutasteride and tamsulosin from 3 months and 12 months, respectively. Similarly, the improvement in the voiding subscore with combined therapy was significantly better than Dutasteride (P < 0.001) and tamsulosin (P ≤ 0.006) from 3 months and 6 months, respectively. •  Improvements in the storage and voiding symptom subscores with combined therapy were achieved irrespective of prostate volume, although in men with the highest baseline prostate volumes (≥58 mL), combined therapy was not better than Dutasteride. CONCLUSIONS •  In men with a prostate volume of ≥30 mL, combined therapy with Dutasteride plus tamsulosin provided better long-term (up to 4 years) control of both storage and voiding LUTS compared with tamsulosin monotherapy. •  Combined therapy was better than Dutasteride monotherapy in men with prostate volumes of ≥30 to <58 mL, but not in men with a prostate volume of ≥58 mL.

  • effect of Dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the combination of avodart and tamsulosin trial
    European Urology, 2011
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Gerald L Andriole, Ramiro Castro, Roger S Rittmaster
    Abstract:

    Abstract Background A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receiving Dutasteride in the 4-yr Reduction by Dutasteride of Prostate Cancer Events study, in whom biopsies were protocol dependent. Objective Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause. Design, setting, and participants CombAT was a 4-yr randomized double-blind parallel group study in 4844 men ≥50 yr of age with clinically diagnosed moderate to severe BPH, International Prostate Symptom Score ≥12, prostate volume ≥30ml, and serum prostate-specific antigen (PSA) 1.5–10 ng/ml. Men underwent annual PSA measurement and digital rectal examination (DRE), and prostate biopsies were performed for cause. Intervention All patients took tamsulosin 0.4mg/d, Dutasteride 0.5mg/d, or a combination of both. Measurements The primary end point was incidence of PCa. Secondary end points included postbaseline prostate biopsy rates and Gleason score of cancers. Results and limitations Dutasteride (alone or in combination with tamsulosin) was associated with a 40% RRR of PCa diagnosis compared with tamsulosin monotherapy (95% confidence interval, 16–57%; p =0.002) and a 40% reduction in the likelihood of biopsy. There were similar reductions in low- and high-grade Gleason score cancers. The biopsy rate in the groups receiving Dutasteride trended toward a higher diagnostic yield (combination: 29%, Dutasteride: 28%, tamsulosin: 24%). One limitation was the lack of a standardized approach to PCa diagnosis and grading. Conclusions Dutasteride, alone or in combination with tamsulosin, significantly reduced the relative risk of PCa diagnosis in men with BPH undergoing annual DRE and PSA screening. Consistent with the increased usefulness of PSA for PCa detection, men receiving Dutasteride had a numerically lower biopsy rate and higher yield of PCa on biopsy. Trial registration Clinicaltrials.gov identifier: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).

Roger S Rittmaster - One of the best experts on this subject based on the ideXlab platform.

  • usefulness of prostate specific antigen psa rise as a marker of prostate cancer in men treated with Dutasteride lessons from the reduce study
    BJUI, 2012
    Co-Authors: Michael Marberger, Francesco Montorsi, Roger S Rittmaster, Gerald L Andriole, Curtis A Pettaway, Claudio Teloken, Stephen J. Freedland, Matthew C. Somerville, Mark Emberton, Ramiro Castro
    Abstract:

    Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of Dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as Dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the Dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with Dutasteride treatment. OBJECTIVES • To determine if Dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. • To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers. PATIENTS AND METHODS • The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether Dutasteride (0.5 mg/day) reduced the risk of biopsy-detectable prostate cancer in men with a previous negative biopsy. • The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the Dutasteride group. • The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. • Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. RESULTS • Of 8231 men randomized, 3305 (Dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. • If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the Dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. • In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. • Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with Dutasteride vs placebo. • Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. CONCLUSION • Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with Dutasteride compared with placebo in men with a previous negative biopsy. • The sensitivity of PSA kinetics with Dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the Dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.

  • comparison of Dutasteride and finasteride for treating benign prostatic hyperplasia the enlarged prostate international comparator study epics
    BJUI, 2011
    Co-Authors: Curtis J Nickel, Teuvo L J Tammela, Peter Gilling, Betsy Morrill, Timothy H Wilson, Roger S Rittmaster
    Abstract:

    Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Both Dutasteride and finasteride inhibit type 2 5α-reductase, the dominant form of 5α-reductase in benign prostatic tissue, making these effective treatments for BPH. In comparison with finasteride, Dutasteride has a longer half-life and leads to a greater and more consistent suppression of serum and intraprostatic DHT. EPICS is currently the only prospective, randomized, double-blind study of finasteride vs Dutasteride for BPH endpoints conducted for longer than a few months. Over a one-year period, treatment with Dutasteride and finasteride led to similar reductions in prostate volume, and improvements in peak urine flow and urinary symptoms associated with BPH in men with an enlarged prostate. Men treated with finasteride and Dutasteride also experienced similar rates of adverse events over the course of one year, which suggests that inhibition of both type 1 and type 2 5α-reductase, resulting in greater DHT suppression than type 2 inhibition alone, does not confer an increase in adverse events. Given the long-term, progressive nature of BPH, the one-year duration of EPICS may limit the potential to observe major differences between Dutasteride and finasteride treatment. OBJECTIVE • To assess the efficacy and safety of Dutasteride compared with finasteride in treating men with symptomatic benign prostatic hyperplasia (BPH) for 12 months. PATIENTS AND METHODS • The Enlarged Prostate International Comparator Study was a multicentre, randomized, double-blind, 12-month, parallel-group study. • Men aged ≥50 years with a clinical diagnosis of BPH received once-daily treatment with Dutasteride 0.5 mg (n= 813) or finasteride 5 mg (n= 817). After a 4-week placebo run-in period, patients were randomized to receive Dutasteride or finasteride for 48 weeks, followed by an optional 24-month, open-label phase, during which patients received Dutasteride 0.5 mg once daily. • The primary endpoint was change in prostate volume, and the secondary endpoints included improvement in American Urological Association Symptom Index (AUA-SI) scores, improvement in maximum urinary flow rate (Qmax) and long-term safety in the 24-month open-label phase. RESULTS • Both Dutasteride and finasteride were effective at reducing prostate volume with no significant difference between the two treatments during the study. • Similar reductions in mean AUA-SI scores and Qmax were also observed for men in both treatment groups. • A similar percentage of adverse events was experienced by patients of both treatment groups, and no new adverse events were reported in the open-label phase. CONCLUSION • Dutasteride and finasteride, when administered for 12 months, were similarly effective in reducing prostate volume and improving Qmax and urinary symptoms associated with BPH in men with an enlarged prostate.

  • Dutasteride improves outcomes of benign prostatic hyperplasia when evaluated for prostate cancer risk reduction: secondary analysis of the REduction by Dutasteride of prostate Cancer Events (REDUCE) trial.
    Urology, 2011
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Gerald L Andriole, J. Curtis Nickel, R. Paul Gagnier, Libby Black, Roger S Rittmaster
    Abstract:

    Objective To investigate the effect of Dutasteride versus placebo on the symptoms and associated complications of male lower urinary tract symptoms and benign prostatic hyperplasia (BPH) across a range of prostate volumes and BPH symptoms in men evaluated for prostate cancer risk reduction in the 4-year REduction by Dutasteride of prostate Cancer Events (REDUCE) trial. Methods REDUCE was a multicenter, randomized, double-blind, placebo-controlled study of prostate cancer risk reduction with daily Dutasteride 0.5 mg or placebo. Eligible men were aged 50-75 years, with a prostate-specific antigen level of 2.5-10 ng/mL and a prostate volume of ≤80 cm 3 . The prespecified and post hoc analyses were performed on the incidence of acute urinary retention, BPH-related surgery, and urinary tract infections, as well as on changes in prostate volume, International Prostate Symptom Score, BPH Impact Index, and maximal urinary flow rate (Qmax). Results A total of 8122 men were included in the efficacy population. During the 4-year study, the International Prostate Symptom Score increased in placebo-treated patients, while Dutasteride-treated patients had a stabilized or decreased International Prostate Symptom Score and improved BPH Impact Index and quality of life due to urinary symptom scores across all prostate volume quintiles (including prostate glands smaller than those studied in previous Dutasteride trials). 48 months, the incidence of acute urinary retention or BPH-related surgery was significantly less in the Dutasteride group (2.5%) than in the placebo group (9%) overall ( P P Conclusion During the 4-year study, Dutasteride was associated with a decreased risk of BPH progression in men with mild-to-moderate symptoms and normal or enlarged prostates.

  • effect of Dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the combination of avodart and tamsulosin trial
    European Urology, 2011
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Gerald L Andriole, Ramiro Castro, Roger S Rittmaster
    Abstract:

    Abstract Background A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receiving Dutasteride in the 4-yr Reduction by Dutasteride of Prostate Cancer Events study, in whom biopsies were protocol dependent. Objective Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause. Design, setting, and participants CombAT was a 4-yr randomized double-blind parallel group study in 4844 men ≥50 yr of age with clinically diagnosed moderate to severe BPH, International Prostate Symptom Score ≥12, prostate volume ≥30ml, and serum prostate-specific antigen (PSA) 1.5–10 ng/ml. Men underwent annual PSA measurement and digital rectal examination (DRE), and prostate biopsies were performed for cause. Intervention All patients took tamsulosin 0.4mg/d, Dutasteride 0.5mg/d, or a combination of both. Measurements The primary end point was incidence of PCa. Secondary end points included postbaseline prostate biopsy rates and Gleason score of cancers. Results and limitations Dutasteride (alone or in combination with tamsulosin) was associated with a 40% RRR of PCa diagnosis compared with tamsulosin monotherapy (95% confidence interval, 16–57%; p =0.002) and a 40% reduction in the likelihood of biopsy. There were similar reductions in low- and high-grade Gleason score cancers. The biopsy rate in the groups receiving Dutasteride trended toward a higher diagnostic yield (combination: 29%, Dutasteride: 28%, tamsulosin: 24%). One limitation was the lack of a standardized approach to PCa diagnosis and grading. Conclusions Dutasteride, alone or in combination with tamsulosin, significantly reduced the relative risk of PCa diagnosis in men with BPH undergoing annual DRE and PSA screening. Consistent with the increased usefulness of PSA for PCa detection, men receiving Dutasteride had a numerically lower biopsy rate and higher yield of PCa on biopsy. Trial registration Clinicaltrials.gov identifier: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).

  • Effect of Dutasteride on Intraprostatic Androgen Levels in Men With Benign Prostatic Hyperplasia or Prostate Cancer
    Urology, 2008
    Co-Authors: Roger S Rittmaster, Robert G. Hahn, Paul Ray, Jennifer B. Shannon, R Wurzel
    Abstract:

    OBJECTIVES Dutasteride exerts its beneficial effects on the prostate through suppression of intraprostatic dihydrotestosterone (DHT). The aim of this analysis was to assess the effects of the approved dose of Dutasteride (0.5 mg/d), given for 2 weeks to 4 months, on the serum and intraprostatic DHT and testosterone levels in 3 randomized studies. METHODS Intraprostatic androgen levels were measured in benign prostatic tissue collected during transurethral resection of the prostate (benign prostatic hyperplasia studies, n = 256) or radical prostatectomy (prostate cancer study, n = 51), performed after 2 weeks, or 1, 3, or 4 months of treatment with Dutasteride or with placebo or surgery alone. The serum androgen levels were assessed at the same points during treatment. Data from the control groups were pooled to provide 1 comparison group. RESULTS Dutasteride reduced the intraprostatic DHT levels by 83%, 90%, 92%, and 93% after 2 weeks and 1, 3, and 4 months of treatment, respectively, compared with placebo/surgery alone. Dutasteride reduced the serum DHT levels from baseline by 84% at 2 weeks and by approximately 90% at 1, 2, 3, and 4 months compared with a 5.2% increase in the control group. The decrease in DHT levels with Dutasteride was accompanied by a reciprocal increase in the serum and intraprostatic testosterone levels. However, the intraprostatic testosterone levels in the Dutasteride groups generally remained lower than the intraprostatic DHT levels in the control group. CONCLUSIONS The results of our study have shown that Dutasteride provides near-maximal suppression of both serum and intraprostatic DHT levels in men with benign prostatic hyperplasia or prostate cancer at all points assessed.

Gerald L Andriole - One of the best experts on this subject based on the ideXlab platform.

  • alcohol intake increases high grade prostate cancer risk among men taking Dutasteride in the reduce trial
    European Urology, 2014
    Co-Authors: Jay H Fowke, Gerald L Andriole, Stephen J. Freedland, Lauren E Howard
    Abstract:

    Abstract Background Although most studies found no association between alcohol intake and prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial found that high alcohol intake significantly increased PCa risk among men randomized to the 5α-reductase inhibitor (5-ARI) finasteride. Objective Determine whether alcohol affects PCa risk among men taking the 5-ARI Dutasteride. Design, settings, and participants Reduction by Dutasteride of Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo-controlled trial to compare PCa after Dutasteride administration (0.5mg/d) with placebo. Participants had a baseline prostate-specific antigen between 2.5 and 10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PCa status at 2 yr and 4 yr of follow-up. Outcome measurements and statistical analysis Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between alcohol intake and low-grade (Gleason 7) PCa. Results and limitations Of 6374 participants in our analysis, approximately 25% reported no alcohol consumption, 49% were moderate drinkers (one to seven drinks per week), and 26% were heavy drinkers (more than seven drinks per week). Alcohol intake was not associated with low- or high-grade PCa in the placebo arm and was not associated with low-grade PCa among men taking Dutasteride. In contrast, men randomized to Dutasteride and reporting more than seven drinks per week were 86% more likely to be diagnosed with high-grade PCa ( p =0.01). Among alcohol abstainers, Dutasteride was associated with significantly reduced risk of high-grade PCa (OR: 0.59; 95% CI, 0.38–0.90), but Dutasteride was no longer associated with reduced high-grade PCa among men reporting high alcohol intake (OR: 0.99; 95% CI, 0.67–1.45). Conclusions Alcohol consumption negated a protective association between Dutasteride and high-grade PCa. Patient summary We confirmed a prior study that alcohol affects PCa prevention in patients taking 5-ARIs. Patients taking 5-ARIs may wish to eliminate alcohol intake if they are concerned about PCa.

  • Obesity is associated with increased prostate growth and attenuated prostate volume reduction by Dutasteride.
    European urology, 2013
    Co-Authors: Roberto L. Muller, Neil Fleshner, Gerald L Andriole, Leah R. Gerber, Daniel M. Moreira, Robert J. Hamilton, J. Kellogg Parsons, Stephen J. Freedland
    Abstract:

    Abstract Background Although obesity has been associated with larger prostate volumes (PV), few studies have actually investigated whether obesity enhances PV growth, especially among men using 5α-reductase inhibitors. Objective To examine whether obesity is associated with enhanced PV growth measured by serial transrectal ultrasound (TRUS) measurements. Design, setting, and participants We conducted a secondary analysis of the REduction by Dutasteride of prostate Cancer Events (REDUCE) trial, which was originally aimed at cancer risk reduction among high-risk men with a single negative prestudy biopsy. Intervention Per-protocol randomization to placebo or Dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr. Outcome measurements and statistical analysis Percentage change in PV at 2 yr and 4 yr from baseline. We tested its association with baseline body mass index (BMI) groups of 2 using multivariable linear regression. Secondarily, we tested whether BMI was associated with the likelihood of having no PV reduction among men randomized to Dutasteride using multivariable logistic regression. Results and limitations Of 8122 participants, we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In multivariable analysis, men on placebo with BMI ≥30 versus 2 had enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p p =0.001). Men on Dutasteride with BMI ≥30 versus 2 had attenuated PV reduction from baseline (at 2 yr: −14.3% vs −18.5%; p =0.002; at 4 yr: −13.2% vs −19.3%; p =0.001) and higher likelihood of having no PV reduction (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08–1.93; p =0.014; at 4 yr: OR: 1.62; 95% CI, 1.18–2.22; p =0.003). We found no significant interactions between BMI and Dutasteride on PV change at 2 yr and 4 yr ( p interaction ≥0.36). No clinical outcomes or effects of weight change were assessed. Conclusions Obesity enhanced PV growth and attenuated PV reduction by Dutasteride. The null interaction between obesity and Dutasteride for PV change implies that the effect of obesity on Dutasteride-treated men is likely a combination of Dutasteride-driven PV reduction with obesity-driven PV growth rather than decreased Dutasteride efficacy. ClinicalTrials.gov identifier NCT00056407.

  • usefulness of prostate specific antigen psa rise as a marker of prostate cancer in men treated with Dutasteride lessons from the reduce study
    BJUI, 2012
    Co-Authors: Michael Marberger, Francesco Montorsi, Roger S Rittmaster, Gerald L Andriole, Curtis A Pettaway, Claudio Teloken, Stephen J. Freedland, Matthew C. Somerville, Mark Emberton, Ramiro Castro
    Abstract:

    Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of Dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as Dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the Dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with Dutasteride treatment. OBJECTIVES • To determine if Dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. • To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers. PATIENTS AND METHODS • The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether Dutasteride (0.5 mg/day) reduced the risk of biopsy-detectable prostate cancer in men with a previous negative biopsy. • The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the Dutasteride group. • The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. • Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. RESULTS • Of 8231 men randomized, 3305 (Dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. • If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the Dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. • In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. • Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with Dutasteride vs placebo. • Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. CONCLUSION • Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with Dutasteride compared with placebo in men with a previous negative biopsy. • The sensitivity of PSA kinetics with Dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the Dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.

  • Dutasteride improves outcomes of benign prostatic hyperplasia when evaluated for prostate cancer risk reduction: secondary analysis of the REduction by Dutasteride of prostate Cancer Events (REDUCE) trial.
    Urology, 2011
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Gerald L Andriole, J. Curtis Nickel, R. Paul Gagnier, Libby Black, Roger S Rittmaster
    Abstract:

    Objective To investigate the effect of Dutasteride versus placebo on the symptoms and associated complications of male lower urinary tract symptoms and benign prostatic hyperplasia (BPH) across a range of prostate volumes and BPH symptoms in men evaluated for prostate cancer risk reduction in the 4-year REduction by Dutasteride of prostate Cancer Events (REDUCE) trial. Methods REDUCE was a multicenter, randomized, double-blind, placebo-controlled study of prostate cancer risk reduction with daily Dutasteride 0.5 mg or placebo. Eligible men were aged 50-75 years, with a prostate-specific antigen level of 2.5-10 ng/mL and a prostate volume of ≤80 cm 3 . The prespecified and post hoc analyses were performed on the incidence of acute urinary retention, BPH-related surgery, and urinary tract infections, as well as on changes in prostate volume, International Prostate Symptom Score, BPH Impact Index, and maximal urinary flow rate (Qmax). Results A total of 8122 men were included in the efficacy population. During the 4-year study, the International Prostate Symptom Score increased in placebo-treated patients, while Dutasteride-treated patients had a stabilized or decreased International Prostate Symptom Score and improved BPH Impact Index and quality of life due to urinary symptom scores across all prostate volume quintiles (including prostate glands smaller than those studied in previous Dutasteride trials). 48 months, the incidence of acute urinary retention or BPH-related surgery was significantly less in the Dutasteride group (2.5%) than in the placebo group (9%) overall ( P P Conclusion During the 4-year study, Dutasteride was associated with a decreased risk of BPH progression in men with mild-to-moderate symptoms and normal or enlarged prostates.

  • effect of Dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the combination of avodart and tamsulosin trial
    European Urology, 2011
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Gerald L Andriole, Ramiro Castro, Roger S Rittmaster
    Abstract:

    Abstract Background A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receiving Dutasteride in the 4-yr Reduction by Dutasteride of Prostate Cancer Events study, in whom biopsies were protocol dependent. Objective Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause. Design, setting, and participants CombAT was a 4-yr randomized double-blind parallel group study in 4844 men ≥50 yr of age with clinically diagnosed moderate to severe BPH, International Prostate Symptom Score ≥12, prostate volume ≥30ml, and serum prostate-specific antigen (PSA) 1.5–10 ng/ml. Men underwent annual PSA measurement and digital rectal examination (DRE), and prostate biopsies were performed for cause. Intervention All patients took tamsulosin 0.4mg/d, Dutasteride 0.5mg/d, or a combination of both. Measurements The primary end point was incidence of PCa. Secondary end points included postbaseline prostate biopsy rates and Gleason score of cancers. Results and limitations Dutasteride (alone or in combination with tamsulosin) was associated with a 40% RRR of PCa diagnosis compared with tamsulosin monotherapy (95% confidence interval, 16–57%; p =0.002) and a 40% reduction in the likelihood of biopsy. There were similar reductions in low- and high-grade Gleason score cancers. The biopsy rate in the groups receiving Dutasteride trended toward a higher diagnostic yield (combination: 29%, Dutasteride: 28%, tamsulosin: 24%). One limitation was the lack of a standardized approach to PCa diagnosis and grading. Conclusions Dutasteride, alone or in combination with tamsulosin, significantly reduced the relative risk of PCa diagnosis in men with BPH undergoing annual DRE and PSA screening. Consistent with the increased usefulness of PSA for PCa detection, men receiving Dutasteride had a numerically lower biopsy rate and higher yield of PCa on biopsy. Trial registration Clinicaltrials.gov identifier: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).

Timothy Wilson - One of the best experts on this subject based on the ideXlab platform.

  • influence of baseline variables on changes in international prostate symptom score after combined therapy with Dutasteride plus tamsulosin or either monotherapy in patients with benign prostatic hyperplasia and lower urinary tract symptoms 4 year res
    BJUI, 2014
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Jack Barkin, Mark Emberton, Andrea Tubaro, Betsy Brotherton, Ramiro Castro
    Abstract:

    Objective To examine, using post hoc analysis, the influence of baseline variables on changes in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax) and IPSS quality of life (QoL) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with either the α-blocker tamsulosin or the dual 5-alpha reductase inhibitor Dutasteride, alone or in combination, as part of the 4-year Combination of Avodart and Tamsulosin (CombAT) study. Patients and Methods CombAT was a 4-year, multicentre, randomized, double-blind, parallel-group study in 4844 men ≥50 years of age with a clinical diagnosis of BPH by medical history and physical examination, an IPSS ≥12 points, prostate volume (PV) ≥30 mL, total serum PSA level ≥1.5 ng/mL, and Qmax >5 mL/s and ≤15 mL/s with a minimum voided volume ≥125 mL. Eligible subjects were randomized to receive oral daily tamsulosin, 0.4 mg; Dutasteride, 0.5 mg; or a combination of both. Baseline variable subgroups analysed were as follows: PV (30 to <40; 40 to <60; 60 to <80; ≥80 mL), PSA level (1.5 to <2.5; 2.5 to <4; ≥4 ng/mL), age (median: <66, ≥66 years), IPSS (median: <16, ≥16; IPSS thresholds, <20, ≥20), IPSS QoL score (question 8, Q8) (median: <4, ≥4), Qmax (median: <10.4, ≥10.4 mL/s), BPH impact index (BII) (median: <5, ≥5) and body mass index (BMI, median: <26.8, ≥26.8 kg/m2). Within each baseline variable subgroup, changes in IPSS, Qmax and IPSS QoL Q8 from baseline were evaluated using a generalized linear model with effects for baseline IPSS, Qmax or IPSS QoL Q8 and treatment group at each post-baseline assessment up to and including the month 48 visit using a last observation carried forward approach. The treatment comparisons of combination therapy vs Dutasteride and combination therapy vs tamsulosin were performed from the general linear model with statistical significance defined as P ≤ 0.01. Results Combination therapy resulted in a significantly greater improvement from baseline IPSS at 48 months vs tamsulosin monotherapy across all baseline subgroups. The benefit of combination therapy over Dutasteride was confined to groups with lower baseline PV (<60 mL) and PSA (<4 ng/mL). In groups with baseline PV ≥60 mL and PSA ≥4 ng/mL, Dutasteride and combination therapy show similar improvements in symptoms. Combination therapy resulted in significantly improved Qmax compared with tamsulosin but not Dutasteride monotherapy. Qmax improvement appeared to increase with PV and PSA level in combination therapy subjects. The proportion of subjects with an IPSS QoL ≤2 (at least mostly satisfied) at 48 months was significantly higher with combination therapy than with Dutasteride for subgroups with PV 40–60 mL and PSA level <4 ng/mL and than with tamsulosin for all PSA subgroups and PV subgroups ≥40 mL. Conclusions CombAT data support the use of long-term combination therapy with Dutasteride and tamsulosin in patients considered at risk for progression of BPH, as determined by high PV (≥30 mL) and high PSA (≥1.5 ng/mL). Combination therapy, Dutasteride monotherapy and tamsulosin monotherapy all improved Qmax, but to different extents (combination therapy > Dutasteride >> tamsulosin), suggesting that Dutasteride contributes most to the Qmax benefit in combination therapy. Combination therapy provided consistent improvement over tamsulosin in LUTS across all analysed baseline variables at 48 months. Compared with Dutasteride, the superiority of combination therapy at 48 months was shown in patients with PV <60 mL or PSA <4 ng/mL.

  • The effect of Dutasteride on the detection of prostate cancer: A set of meta-analyses.
    Canadian Urological Association journal = Journal de l'Association des urologues du Canada, 2013
    Co-Authors: Neerav Monga, Amyn Sayani, Daniel A. Rubinger, Timothy Wilson
    Abstract:

    Background: 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 meta analysis 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 GlaxoSmithKline sponsored phase III randomized clinical trials (with a study duration of ≥2 years) evaluating the effect of Dutasteride, alone or incombination 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. Results: The meta-analysis demonstrated that in a population with symptomatic BPH and/or at increased risk of prostate cancer, a statistically significant lower number of detectable prostate cancers was found in men taking Dutasteride compared to control groups (MHRR: 0.66, 95% CI 0.52-0.85). In our analysis, there was no increased risk for Gleason 7-10 (MHRR: 0.83, 95% CI 0.56-1.21) or Gleason 8-10 prostate cancers (MHRR: 0.99, 95% CI 0.39-2.53) in men taking Dutasteride over control groups. There were several limitations that need to be considered when interpreting these results. Conclusion: These data provide support for the continued use of Dutasteride in the treatment of symptomatic BPH patients.

  • Dutasteride improves outcomes of benign prostatic hyperplasia when evaluated for prostate cancer risk reduction: secondary analysis of the REduction by Dutasteride of prostate Cancer Events (REDUCE) trial.
    Urology, 2011
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Gerald L Andriole, J. Curtis Nickel, R. Paul Gagnier, Libby Black, Roger S Rittmaster
    Abstract:

    Objective To investigate the effect of Dutasteride versus placebo on the symptoms and associated complications of male lower urinary tract symptoms and benign prostatic hyperplasia (BPH) across a range of prostate volumes and BPH symptoms in men evaluated for prostate cancer risk reduction in the 4-year REduction by Dutasteride of prostate Cancer Events (REDUCE) trial. Methods REDUCE was a multicenter, randomized, double-blind, placebo-controlled study of prostate cancer risk reduction with daily Dutasteride 0.5 mg or placebo. Eligible men were aged 50-75 years, with a prostate-specific antigen level of 2.5-10 ng/mL and a prostate volume of ≤80 cm 3 . The prespecified and post hoc analyses were performed on the incidence of acute urinary retention, BPH-related surgery, and urinary tract infections, as well as on changes in prostate volume, International Prostate Symptom Score, BPH Impact Index, and maximal urinary flow rate (Qmax). Results A total of 8122 men were included in the efficacy population. During the 4-year study, the International Prostate Symptom Score increased in placebo-treated patients, while Dutasteride-treated patients had a stabilized or decreased International Prostate Symptom Score and improved BPH Impact Index and quality of life due to urinary symptom scores across all prostate volume quintiles (including prostate glands smaller than those studied in previous Dutasteride trials). 48 months, the incidence of acute urinary retention or BPH-related surgery was significantly less in the Dutasteride group (2.5%) than in the placebo group (9%) overall ( P P Conclusion During the 4-year study, Dutasteride was associated with a decreased risk of BPH progression in men with mild-to-moderate symptoms and normal or enlarged prostates.

  • the effects of Dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms luts and benign prostatic hyperplasia bph 4 year data from the combination of avodart and tamsulosin combat stu
    BJUI, 2011
    Co-Authors: Francesco Montorsi, Claus G Roehrborn, Javier Garciapenit, Michael Borre, Ton A Roeleveld, Jean Charles Alimi, Paul Gagnier, Timothy Wilson
    Abstract:

    Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Long-term treatment with combination therapy (Dutasteride plus tamsulosin) is significantly superior to tamsulosin but not Dutasteride at reducing the relative risk of AUR or BPH-related surgery. Furthermore, combination therapy is significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression, and provides significantly greater reductions in IPSS. In addition, combination therapy significantly improves patient-reported, disease specific QoL and treatment satisfaction compared with either monotherapy. Two-year results from the CombAT study showed that combination therapy was more effective than either monotherapy in controlling both storage and voiding symptoms, irrespective of baseline prostate volume (for men with prostate volume ≥30 cc). This post-hoc two-year analysis also showed that treatment with Dutasteride not only improved voiding symptoms, as would be expected from its effects on prostate volume, but was also as effective as the α-blocker tamsulosin in the control of storage symptoms. OBJECTIVE •  To assess the effects of combined therapy with Dutasteride and tamsulosin on voiding and storage symptoms compared with those of Dutasteride or tamsulosin alone, using 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. PATIENTS AND METHODS •  Men (n = 4844) aged ≥50 years with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH), a prostate volume of ≥30 mL, and a serum prostate-specific antigen level of 1.5–10 ng/mL. •  CombAT was a multicentre, double-blind, parallel-group study. •  Oral Dutasteride (0.5 mg) or tamsulosin (0.4 mg) alone or in combination was taken daily for 4 years. •  Mean changes from baseline in storage and voiding symptoms at 4 years were assessed using subscales of the International Prostate Symptom Score. RESULTS •  At 4 years, the mean reduction in the storage subscore was significantly greater in the combined therapy group vs the Dutasteride (adjusted mean difference −0.43) and tamsulosin (adjusted mean difference −0.96) monotherapy groups (P < 0.001). •  Also at 4 years, the mean reduction in the voiding subscore was significantly greater in the combined therapy group vs the Dutasteride (adjusted mean difference −0.51) and tamsulosin (adjusted mean difference −1.60) monotherapy groups (P < 0.001). •  The improvement in the storage subscore with combined therapy was significantly better (P < 0.001) than Dutasteride and tamsulosin from 3 months and 12 months, respectively. Similarly, the improvement in the voiding subscore with combined therapy was significantly better than Dutasteride (P < 0.001) and tamsulosin (P ≤ 0.006) from 3 months and 6 months, respectively. •  Improvements in the storage and voiding symptom subscores with combined therapy were achieved irrespective of prostate volume, although in men with the highest baseline prostate volumes (≥58 mL), combined therapy was not better than Dutasteride. CONCLUSIONS •  In men with a prostate volume of ≥30 mL, combined therapy with Dutasteride plus tamsulosin provided better long-term (up to 4 years) control of both storage and voiding LUTS compared with tamsulosin monotherapy. •  Combined therapy was better than Dutasteride monotherapy in men with prostate volumes of ≥30 to <58 mL, but not in men with a prostate volume of ≥58 mL.

  • effect of Dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the combination of avodart and tamsulosin trial
    European Urology, 2011
    Co-Authors: Claus G Roehrborn, Timothy Wilson, Gerald L Andriole, Ramiro Castro, Roger S Rittmaster
    Abstract:

    Abstract Background A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receiving Dutasteride in the 4-yr Reduction by Dutasteride of Prostate Cancer Events study, in whom biopsies were protocol dependent. Objective Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause. Design, setting, and participants CombAT was a 4-yr randomized double-blind parallel group study in 4844 men ≥50 yr of age with clinically diagnosed moderate to severe BPH, International Prostate Symptom Score ≥12, prostate volume ≥30ml, and serum prostate-specific antigen (PSA) 1.5–10 ng/ml. Men underwent annual PSA measurement and digital rectal examination (DRE), and prostate biopsies were performed for cause. Intervention All patients took tamsulosin 0.4mg/d, Dutasteride 0.5mg/d, or a combination of both. Measurements The primary end point was incidence of PCa. Secondary end points included postbaseline prostate biopsy rates and Gleason score of cancers. Results and limitations Dutasteride (alone or in combination with tamsulosin) was associated with a 40% RRR of PCa diagnosis compared with tamsulosin monotherapy (95% confidence interval, 16–57%; p =0.002) and a 40% reduction in the likelihood of biopsy. There were similar reductions in low- and high-grade Gleason score cancers. The biopsy rate in the groups receiving Dutasteride trended toward a higher diagnostic yield (combination: 29%, Dutasteride: 28%, tamsulosin: 24%). One limitation was the lack of a standardized approach to PCa diagnosis and grading. Conclusions Dutasteride, alone or in combination with tamsulosin, significantly reduced the relative risk of PCa diagnosis in men with BPH undergoing annual DRE and PSA screening. Consistent with the increased usefulness of PSA for PCa detection, men receiving Dutasteride had a numerically lower biopsy rate and higher yield of PCa on biopsy. Trial registration Clinicaltrials.gov identifier: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).

Stephen J. Freedland - One of the best experts on this subject based on the ideXlab platform.

  • alcohol intake increases high grade prostate cancer risk among men taking Dutasteride in the reduce trial
    European Urology, 2014
    Co-Authors: Jay H Fowke, Gerald L Andriole, Stephen J. Freedland, Lauren E Howard
    Abstract:

    Abstract Background Although most studies found no association between alcohol intake and prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial found that high alcohol intake significantly increased PCa risk among men randomized to the 5α-reductase inhibitor (5-ARI) finasteride. Objective Determine whether alcohol affects PCa risk among men taking the 5-ARI Dutasteride. Design, settings, and participants Reduction by Dutasteride of Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo-controlled trial to compare PCa after Dutasteride administration (0.5mg/d) with placebo. Participants had a baseline prostate-specific antigen between 2.5 and 10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PCa status at 2 yr and 4 yr of follow-up. Outcome measurements and statistical analysis Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between alcohol intake and low-grade (Gleason 7) PCa. Results and limitations Of 6374 participants in our analysis, approximately 25% reported no alcohol consumption, 49% were moderate drinkers (one to seven drinks per week), and 26% were heavy drinkers (more than seven drinks per week). Alcohol intake was not associated with low- or high-grade PCa in the placebo arm and was not associated with low-grade PCa among men taking Dutasteride. In contrast, men randomized to Dutasteride and reporting more than seven drinks per week were 86% more likely to be diagnosed with high-grade PCa ( p =0.01). Among alcohol abstainers, Dutasteride was associated with significantly reduced risk of high-grade PCa (OR: 0.59; 95% CI, 0.38–0.90), but Dutasteride was no longer associated with reduced high-grade PCa among men reporting high alcohol intake (OR: 0.99; 95% CI, 0.67–1.45). Conclusions Alcohol consumption negated a protective association between Dutasteride and high-grade PCa. Patient summary We confirmed a prior study that alcohol affects PCa prevention in patients taking 5-ARIs. Patients taking 5-ARIs may wish to eliminate alcohol intake if they are concerned about PCa.

  • Obesity is associated with increased prostate growth and attenuated prostate volume reduction by Dutasteride.
    European urology, 2013
    Co-Authors: Roberto L. Muller, Neil Fleshner, Gerald L Andriole, Leah R. Gerber, Daniel M. Moreira, Robert J. Hamilton, J. Kellogg Parsons, Stephen J. Freedland
    Abstract:

    Abstract Background Although obesity has been associated with larger prostate volumes (PV), few studies have actually investigated whether obesity enhances PV growth, especially among men using 5α-reductase inhibitors. Objective To examine whether obesity is associated with enhanced PV growth measured by serial transrectal ultrasound (TRUS) measurements. Design, setting, and participants We conducted a secondary analysis of the REduction by Dutasteride of prostate Cancer Events (REDUCE) trial, which was originally aimed at cancer risk reduction among high-risk men with a single negative prestudy biopsy. Intervention Per-protocol randomization to placebo or Dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr. Outcome measurements and statistical analysis Percentage change in PV at 2 yr and 4 yr from baseline. We tested its association with baseline body mass index (BMI) groups of 2 using multivariable linear regression. Secondarily, we tested whether BMI was associated with the likelihood of having no PV reduction among men randomized to Dutasteride using multivariable logistic regression. Results and limitations Of 8122 participants, we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In multivariable analysis, men on placebo with BMI ≥30 versus 2 had enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p p =0.001). Men on Dutasteride with BMI ≥30 versus 2 had attenuated PV reduction from baseline (at 2 yr: −14.3% vs −18.5%; p =0.002; at 4 yr: −13.2% vs −19.3%; p =0.001) and higher likelihood of having no PV reduction (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08–1.93; p =0.014; at 4 yr: OR: 1.62; 95% CI, 1.18–2.22; p =0.003). We found no significant interactions between BMI and Dutasteride on PV change at 2 yr and 4 yr ( p interaction ≥0.36). No clinical outcomes or effects of weight change were assessed. Conclusions Obesity enhanced PV growth and attenuated PV reduction by Dutasteride. The null interaction between obesity and Dutasteride for PV change implies that the effect of obesity on Dutasteride-treated men is likely a combination of Dutasteride-driven PV reduction with obesity-driven PV growth rather than decreased Dutasteride efficacy. ClinicalTrials.gov identifier NCT00056407.

  • usefulness of prostate specific antigen psa rise as a marker of prostate cancer in men treated with Dutasteride lessons from the reduce study
    BJUI, 2012
    Co-Authors: Michael Marberger, Francesco Montorsi, Roger S Rittmaster, Gerald L Andriole, Curtis A Pettaway, Claudio Teloken, Stephen J. Freedland, Matthew C. Somerville, Mark Emberton, Ramiro Castro
    Abstract:

    Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of Dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as Dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the Dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with Dutasteride treatment. OBJECTIVES • To determine if Dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. • To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers. PATIENTS AND METHODS • The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether Dutasteride (0.5 mg/day) reduced the risk of biopsy-detectable prostate cancer in men with a previous negative biopsy. • The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the Dutasteride group. • The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. • Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. RESULTS • Of 8231 men randomized, 3305 (Dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. • If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the Dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. • In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. • Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with Dutasteride vs placebo. • Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. CONCLUSION • Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with Dutasteride compared with placebo in men with a previous negative biopsy. • The sensitivity of PSA kinetics with Dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the Dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.

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