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Keywords:

  • benign prostatic hyperplasia;
  • finasteride;
  • dutasteride;
  • 5α-reductase inhibitors

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

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.

Abbreviations
EPICS

Enlarged Prostate International Comparator Study

AUA-SI

AUA Symptom Index

AUR

acute urinary retention

DHT

dihydrotestosterone

5ARI

5α-reductase inhibitor

Qmax

maximum urinary flow rate

ITT

intent- to-treat.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Benign prostatic hyperplasia is a common problem among ageing men. The prevalence of BPH, based on histological evidence from autopsy studies, is >50% in men aged 51–60 and 90% by the age 85 [1]. BPH clinically manifests as LUTS associated with BOO, incomplete bladder emptying and weak stream and hesitancy, all of which affect a man’s health-related quality of life [2,3]. In more advanced cases, acute urinary retention (AUR) can result, the risk of which increases three-fold among men with enlarged prostates (>30 mL) [4].

Dihydrotestosterone (DHT) is the primary androgen responsible for the excessive growth of the prostate that is characteristic of BPH [5]. The conversion of testosterone to DHT is blocked by 5α-reductase inhibitors (5ARIs), which are used to treat BPH [6–8]. Dutasteride, a type 1 and type 2 5ARI, has been shown to provide significantly greater suppression of serum DHT than does finasteride, a type 2 5ARI [9].

This study was designed to assess the efficacy and safety of dutasteride 0.5 mg compared with finasteride 5 mg for 12 months in treating men with BPH, so as to meet the requirements for registering dutasteride for treating symptomatic BPH in countries in the European Union. Prostate volume was selected as the primary endpoint of this study [10,11]. In an optional open-label extension study, men from either treatment group received dutasteride 0.5 mg for an additional 24 months. This optional extension of dutasteride treatment provided an opportunity to investigate the long-term safety and tolerability of dutasteride monotherapy. The Enlarged Prostate International Comparator Study (EPICS) began in 1998, and data from EPICS have been published previously on the GlaxoSmithKline online Clinical Study Register (http://www.gsk-clinicalstudyregister.com). The safety data were published in 2003 [12]. Efficacy data was published as an abstract in the BJUI after presentation at the Urological Society of Australia Annual Scientific Meeting in Melbourne, Australia in 2005 [13]. In addition, efficacy data has been published in several review articles including those by Nickel 2004 [14], Keam and Scott 2008 [15] and Thomson 2005 [16]. As a result of renewed interest within the medical community in EPICS, the authors and GlaxoSmithKline decided to publish the results in a primary peer-reviewed manuscript. EPICS is the only prospective, randomized, double-blind clinical comparison of finasteride and dutasteride conducted over a 12-month period, and it has not been previously published as a primary research paper.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

STUDY POPULATION

Men aged ≥50 years with a clinical diagnosis of BPH according to medical history and physical examination (including DRE) were eligible for the study. Principal inclusion criteria were an AUA Symptom Index (AUA-SI) score ≥12 points at the screening visit, prostate volume ≥30 cm3 assessed by TRUS, two voids with maximum urinary flow rate (Qmax) <15 mL/s and a minimum voided volume of ≥125 mL. Principal exclusion criteria included a post-void residual volume >250 mL, a history or evidence of prostate cancer, previous prostatic surgery or invasive procedure to treat BPH, a history of AUR within 3 months of study entry, and total serum PSA < 1.5 ng/mL or >10.0 ng/mL. Additional exclusion criteria related to previous treatment included use of 5ARIs, use of α-blockers within 2 weeks of the screening visit and throughout the study, use of any α-adrenergic agonists or anticholinergics or cholinergics (within 48 h of all uroflowmetry assessments), use of phytotherapy for BPH within 4 weeks of the screening visit and throughout the study, and concurrent use of drugs with anti-androgenic properties or anabolic steroids.

The study protocol was approved by a national, regional or investigational centre ethics committee or institutional review board. Participants provided written informed consent.

STUDY DESIGN

EPICS was a multicentre, randomized, double-blind, double-dummy, 12-month parallel-group study at 138 centres across Argentina, Austria, Australia, Belgium, Brazil, Canada, Czech Republic, Finland, Germany, Greece, Hungary, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Norway, Portugal, Russia, Singapore, Slovakia, South Africa, Sweden, Taiwan, UK and Ukraine. Eligible patients received once-daily treatment with dutasteride 0.5 mg or finasteride 5 mg. After a 4-week placebo run-in period, patients were randomized to receive dutasteride or finasteride for 48 weeks, with scheduled clinic visits at 3, 6, 9 and 12 months. This was followed by an optional 24-month, open-label phase, during which patients received dutasteride 0.5 mg once daily with 10 scheduled clinic visits at 12 (final visit of the double-blind phase), 15, 18, 21, 24, 27, 30, 33, 36 and 40 months post-randomization. This study began in November 1998 and was completed in October 2000 (double-blind phase) and February 2003 (open phase).

Prostate volume was measured before and after randomization at months 3 and 12. The anteroposterior, cephalocaudal and transverse dimensions of the prostate were obtained by TRUS, and the prostate volume was then calculated according to the formula: π/6 (anteroposterior width × cephalocaudal width × transverse width). Post-void residual volume was measured by ultrasonography at the screening visit, at baseline, and at months 3, 6 and 12. Symptom scores were assessed using the AUA-SI; the questionnaire was self-completed at the screening visit, at baseline and at months 3, 6 and 12. Voided volume and Qmax were assessed at the same time points. PSA levels were measured at the screening visit and at months 3 and 12; the blood samples were taken before TRUS measurements were made.

Safety-related assessments included the reports of adverse events and serious adverse events, laboratory assessments and PSA measurements. During the open-label phase, only safety data was collected.

STUDY ENDPOINTS AND STATISTICAL ANALYSIS

At the preplanned 12-month analysis, the primary endpoint was change in prostate volume. Secondary endpoints included improvement in AUA-SI scores, improvement in Qmax and long-term safety in the 24-month open-label phase. Investigators were responsible for the detection and documentation of adverse and serious adverse events. After the opportunity to spontaneously mention any problems, subjects were queried for adverse events at each visit.

The intent-to-treat (ITT) population consisted of all men randomized to double-blind study treatment. Change and percent change from baseline prostate volume, and AUA-SI and Qmax change from baseline were calculated. Missing values were accounted for using the last observation carried forward. The sample size for the double-blind phase was based upon detecting a 5% difference with regard to the percent change in prostate volume between dutasteride and finasteride at 12 months. The primary comparison was dutasteride vs finasteride, for which the study was powered at 90%, and superiority was based on two-sided P values <0.05. At the time of study design, there was no precedence for percent treatment change in prostate volume using 5ARIs, although it was perceived that finasteride treatment would cause a 20% reduction from baseline prostate volume. Therefore, it was hypothesized that dual inhibition by dutasteride would provide a 5% improvement over finasteride.

Analysis of the primary endpoint – percent change in prostate volume – was conducted using a log-transformed general linear model with effects for treatment, investigative centre geographical cluster and baseline prostate volume. Similarly, adjusted mean changes from baseline were also calculated for AUA-SI and Qmax. All P values were reported and there were no multiplicity controls implemented.

The sample size of the open-label phase was determined by the number of men who completed the double-blind phase and elected to enrol in the open-label phase. The primary population for the open-label phase was the open-label ITT population and consisted of all men who were enrolled in the open-label phase (after completing the 12-month double-blind phase).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

PATIENT DEMOGRAPHICS AND DISPOSITION

Of the 1630 men randomized (the ITT population), 817 received finasteride treatment and 813 received dutasteride treatment (Fig. 1). Of these, 1454 completed the month 12 visit (finasteride group, 735; dutasteride group, 719). There was a similar rate of discontinuation in the finasteride group (10%) compared with the dutasteride (12%) group (P= 0.34). Adverse events were the main reason for discontinuation (finasteride, 4%; dutasteride, 5%).

image

Figure 1. Disposition of the men enrolled in EPICS.

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Eight countries (Brazil, Canada, Czech Republic, Mexico, Norway, Portugal, Slovakia and Ukraine) participated in the open-label phase of the study. Of the men who completed the double-blind phase, 226 men (31%) from the finasteride group and 222 men (31%) from the dutasteride group enrolled in the open-label phase (making a total of 448 in the open-label ITT population). Of these, 371 (83%) completed the month 36 visit, while 77 men (17%) discontinued before this visit (Fig. 1). Adverse events were the main reason for discontinuation (8%) in the open-label phase.

Overall baseline demographics and patient characteristics were similar across treatment groups. Table 1 shows the patient baseline characteristics.

Table 1.  Baseline characteristics of the ITT population in the double-blind and open-label phases of the study
CharacteristicDouble-blind Open-label  
Finasteride, n= 817Dutasteride, n= 813Total, n= 448Finasteride/Dutasteride*, n= 226Dutasteride/Dutasteride, n= 222
  • *

    Subjects received finasteride during double-blind phase and dutasteride during open-label phase.

  • †Subjects received dutasteride during both double-blind and open-label phases of study.

Mean (sd) age, years66.9 (7.37)66.8 (7.18)67.0 (7.28)67.0 (7.21)67.0 (7.36)
Race or ethnic group, n (%)     
 White719 (88)729 (90)401 (90)200 (88)201 (91)
 Black13 (2)8 (<1)9 (2)6 (3)3 (1)
 Asian35 (4)32 (4)1 (<1)0 (0)1 (<1)
 Hispanic29 (4)28 (3)31 (7)16 (7)15 (7)
 Other21 (3)16 (2)6 (1)4 (2)2 (<1)
Mean (sd) AUA-SI score16.5 (5.49)16.7 (5.75)
Mean (sd) Qmax, mL/s10.0 (3.38)10.1 (3.46)
Mean (sd) PVR, mL66.5 (61.78)69.0 (63.55)
Mean (sd) PSA, ng/mL4.3 (2.16)4.3 (2.26)
Mean (sd) prostate volume mean, cm352.4 (19.37)54.2 (21.90)
Mean (sd) duration of BPH symptoms, years4.3 (4.48)4.4 (3.99)4.3 (3.81)4.4 (3.81)4.3 (3.82)

PRIMARY ENDPOINT: REDUCTION IN PROSTATE VOLUME

Both dutasteride and finasteride were effective in reducing prostate volume, with no significant difference between the two treatments (Fig. 2). At month 3, there was an adjusted mean percentage reduction in prostate volume of 18.5% for men in the finasteride group vs 18.3% in the dutasteride group (P= 0.76). At month 12, the reduction was 26.7% in the finasteride group vs 26.3% in the dutasteride group (P= 0.65). The treatment difference at month 12 was 0.4% (CI: 1.4–2.3%).

image

Figure 2. Prostate volume percent change from baseline in the double-blind study.

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Patients in both treatment groups with baseline prostate volumes ≥40 cm3 showed slightly greater reductions in prostate volume at month 12 compared with those with baseline prostate volumes <40 cm3 (Table 2). The percent reduction from baseline in patients with a baseline prostate volume ≥40 cm3 was 27.7% in the finasteride group and 27.6% in the dutasteride group (P= 0.90); for patients with prostate volumes <40 cm3, these reductions were 24.2% and 22.6% for the finasteride and dutasteride groups, respectively (P= 0.37).

Table 2.  Percent change in prostate volume from baseline
 Prostate volume <40 cm3Prostate volume ≥40 cm3
Finasteride, n= 239Dutasteride, n= 233PFinasteride, n= 573Dutasteride, n= 576P
Month 3; n229223 552556 
 Adjusted mean, %–16.6–13.70.10–19.4–20.00.54
Month 12; n230226 558561 
 Adjusted mean, %–24.2–22.60.37–27.7–27.60.90

SECONDARY ENDPOINTS

At month 12, the mean AUA-SI scores were reduced by 5.5 in the finasteride group and 5.8 in the dutasteride group (P= 0.38; Fig. 3). Qmax at month 12 improved by 1.7 mL/s in the finasteride group and by 2.0 mL/s in the dutasteride group (P= 0.14; Fig. 4).

image

Figure 3. AUA-SI score change from baseline in the double-blind study. Error bars indicate SE.

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image

Figure 4. Qmax change from baseline in the double-blind study. Error bars indicate SE.

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In both treatment groups, PSA levels consistently decreased from baseline to months 3 and 12. From baseline, PSA levels in the finasteride group decreased by a mean of 38.9% at month 3 and 47.7% at month 12, while there was a mean decrease of 40.3% at month 3 and 49.5% at month 12 in the dutasteride group.

ADVERSE EVENTS IN THE DOUBLE-BLIND PHASE

During the double-blind treatment phase of the study, 805 men (49%) experienced 1876 adverse events. A similar percentage of adverse events was experienced by patients of both treatment groups and, of all adverse events, none were reported in more than 10% of men. Serious adverse events were reported by 43 patients (5%) in the finasteride group and by 55 patients (7%) in the dutasteride group (Table 3). Drug-related adverse events were reported by 161 patients (20%) in the finasteride group and by 140 (17%) in the dutasteride group. The incidence of sexual adverse events (impotence, decreased libido, ejaculation disorders and sexual function disorders), as well as gynaecomastia, was also similar in each treatment group (Table 4). Prostate cancer was reported in four men from the finasteride group and three men in the dutasteride group.

Table 3.  Adverse events in the double-blind study and open-label phase
Type of AEDouble-blindOpen-label
Finasteride n= 817Dutasteride, n= 813Total, n= 448Finasteride/Dutasteride*n= 226Dutasteride/Dutasteriden= 222
  • *

    Subjects received finasteride during double-blind phase and dutasteride during open-label.

  • †Subjects received dutasteride during both double-blind and open-label phases of study. AE, adverse event.

Any AE, n (%)409 (50)396 (49)200 (45)100 (44)100 (45)
Serious AEs, n (%)43 (5)55 (7)47 (10)26 (12)21 (9)
Drug-related AEs, n (%)161 (20)140 (17)47 (10)19 (8)28 (13)
Drug-related AEs leading to study withdrawal, n (%)16 (2)8 (1)13 (3)7 (3)6 (3)
AEs leading to study withdrawal, n (%)35 (4)38 (5)32 (7)20 (9)12 (5)
Table 4.  Adverse events of special interest during the double-blind or open-label phases of the study by year
Adverse eventDouble-blindOpen-label*
Finasteride Year 1, n= 817Dutasteride Year 1, n= 813Total, n= 448Finasteride/Dutasteride, Years 2 and 3 n= 226Dutasteride/Dutasteride, Years 2 and 3 n= 222
  • *

    Incidence of AUR and prostate surgery not specifically collected in the open-label phase.

  • †Subjects received finasteride during double-blind phase and dutasteride during open-label phase.

  • ‡Subjects received dutasteride during both double-blind and open-label phases of study.

  • §

    All subjects requiring surgery had ≥40 cm3 baseline prostate volumes.

Impotence, n (%)74 (9)63 (8)14 (3)6 (3)8 (4)
Decreased libido, n (%)50 (6)41 (5)5 (1)5 (2)0 (0)
Ejaculation disorders, n (%)14 (2)14 (2)4 (<1)1 (<1)3 (1)
Sexual function disorders, n (%)2 (<1)1 (<1)0 (0)0 (0)0 (0)
Gynaecomastia, n (%)10 (1)9 (1)3 (<1)2 (<1)1 (<1)
Hypertension, n (%)16 (2)19 (2)29 (6)15 (7)14 (6)
AUR, n (%) 11 (1)16 (2)
Prostate surgery§, n (%)1 (<1)2 (<1)
Prostate cancer, n (%)4 (<1)3 (<1)4 (<1)3 (1)1 (<1)

ADVERSE EVENTS IN THE OPEN-LABEL PHASE

In the open-label phase, in which all patients received dutasteride, adverse events were reported in 200 patients (45%) and serious adverse events were reported in 47 patients (10%; Table 3). Hypertension increased from the first year (double-blind phase) to the second and third years (open-label phase) of the study, and was the most commonly reported adverse event during the open-label phase (Table 4). The incidence of new sexual adverse events decreased over time. Four subjects were diagnosed with prostate cancer, including one subject who had previously received dutasteride and three subjects who had previously received finasteride.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Currently, EPICS is the only prospective, randomized, double-blind study of finasteride vs dutasteride for BPH endpoints conducted for longer than a few months. In EPICS, both dutasteride and finasteride treatment resulted in similar reductions in prostate volume. Mean AUA-SI scores improved from baseline at months 3 and 12 in men in the dutasteride and finasteride treatment groups. A notable improvement in Qmax was observed within both treatment groups from baseline, and no statistically significant differences were observed between the groups.

During the 12-month treatment period, there were no differences in the overall numbers of adverse events between the two treatment groups. Once-daily treatment with dutasteride 0.5 mg and finasteride 5 mg resulted in an expected level of adverse events related to sexual function, such as impotence, decreased libido and ejaculation disorders. No notable new adverse events appeared over time.

Both dutasteride and finasteride inhibit type 2 5α-reductase, the dominant form of 5α-reductase in benign prostatic tissue [17–19], making them both effective treatments for BPH. Pharmacological characteristics of dutasteride suggest the possibility of improved outcomes with this treatment. In comparison with finasteride, dutasteride has a longer half-life (termination half-life of approximately 5 weeks vs 6 h), which might lead to better efficacy with dutasteride in patients who take their medication irregularly [20–22]. Dutasteride also leads to a greater and more consistent suppression of serum and intraprostatic DHT [9,23,24]. This study found similar rates of adverse events and sexual adverse events with dutasteride and finasteride treatment. Therefore, 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 [12].

Given the long-term, progressive nature of BPH, the 1-year duration of EPICS may limit the potential to observe major differences between dutasteride and finasteride treatment. As seen in clinical trials of up to 4 years’ duration, BPH symptoms and Qmax may continue to improve over time after the initiation of finasteride or dutasteride therapy [25,26].

Another potential limitation of the present study is the use of prostate volume as a surrogate endpoint for AUR and BPH-related surgery. Prostate volume may not fully correlate with clinical efficacy. For example, the Prospective European Doxazosin and Combination Therapy and the Veterans Affairs Cooperative studies showed no difference between placebo and finasteride at 1 year with respect to total IPSS and Qmax, despite significant differences in prostate volume change [27,28]. Finally, the open-label phase of EPICS provides information on adverse events experienced in men treated with dutasteride for up to 3 years; however, in this phase, patients were no longer blinded to treatment and there was no group for comparison. This limits comparisons that might be made between the double-blind and open-label phases of the study.

In conclusion, the present study suggests that, when given for 1 year, dutasteride and finasteride lead to similar reductions in prostate volume, and improvements in Qmax 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 1 year.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

EPICS was funded by GlaxoSmithKline. Editorial support in the form of assistance with the first draft, collating author comments, assembly of tables and figures, and editorial suggestions to draft versions of this manuscript was provided by Brigitte Teissedre, PhD of Choice Pharma and funded by GlaxoSmithKline. Responsibility for opinions, conclusions and interpretation of data lies with the authors.

CONFLICT OF INTEREST

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

J. Curtis Nickel:

Astellas, consultant

Farr Labs, consultant

Triton and Trillium Therapeutics, consultant

GlaxoSmithKline, consultant/investigator

Johnson and Johnson, consultant/investigator

Pfizer, consultant/investigator

Watson Biomedical, consultant/investigator

Ferring Pharmaceuticals, consultant/investigator

Taris Biomedical, consultant/investigator

Peter Gilling:

Lumenis Inc., meeting participant and study investigator

Teuvo L. Tammela:

Amgen, speaker, advisory board and study investigator

Astellas, speaker and advisory board

AstraZeneca, speaker and study investigator

GlaxoSmithKline, advisory board, speaker and study investigator

Orion Pharma, consultant

Betsy Morrill:

GlaxoSmithKline, employee

GlaxoSmithKline, equity ownership/stock

Timothy H. Wilson:

GlaxoSmithKline, employee

GlaxoSmithKline, equity ownership/stock

Roger S. Rittmaster:

GlaxoSmithKline, employee

GlaxoSmithKline, equity ownership/stock

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES
  • 1
    Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human benign prostatic hyperplasia with age. J Urol 1984; 132: 4749
  • 2
    Anderson JB, Roehrborn CG, Schalken JA, Emberton M. The progression of benign prostatic hyperplasia: examining the evidence and determining the risk. Eur Urol 2001; 39: 3909
  • 3
    AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia. J Urol 2003; 170: 53047
  • 4
    Jacobsen SJ, Jacobson DJ, Girman CJ et al. Natural history of prostatism: risk factors for acute urinary retention. J Urol 1997; 158: 4817
  • 5
    Zhu YS, Imperato-McGinley JL. 5alpha-reductase isozymes and androgen actions in the prostate. Ann N Y Acad Sci 2009; 1155: 4356
  • 6
    Bramson HN, Hermann D, Batchelor KW, Lee FW, James MK, Frye SV. Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR. J Pharmacol Exp Ther 1997; 282: 1496502
  • 7
    Roehrborn CG, Boyle P, Nickel JC et al. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60: 43441
  • 8
    Nickel JC, Fradet Y, Boake RC et al. Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study. CMAJ 1996; 155: 12519
  • 9
    Clark RV, Hermann DJ, Cunningham GR, Wilson TH, Morrill BB, Hobbs S. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab 2004; 89: 217984
  • 10
    Marberger MJ, Andersen JT, Nickel JC et al. Prostate volume and serum prostate-specific antigen as predictors of acute urinary retention. Combined experience from three large multinational placebo-controlled trials. Eur Urol 2000; 38: 5638
  • 11
    Roehrborn CG, McConnell JD, Lieber M et al. Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group. Urology 1999; 53: 47380
  • 12
    Andriole GL, Kirby R. Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol 2003; 44: 828
  • 13
    Gilling P, Jacobi G, Tammela TL, van Erps P. Efficacy of dutasteride and finasteride for the treatment of benign prostate hyperplasia: results of the 1-year Enlarged Prostate International Comparator Study (EPICS). BJU Int 2005; 95: 138; abstract U051
  • 14
    Nickel JC. Comparison of clinical trials with finasteride and dutasteride. Rev Urol 2004; 6 (Suppl. 9): S319
  • 15
    Keam SJ, Scott LJ. Dutasteride: a review of its use in the management of prostate disorders. Drugs 2008; 68: 46385
  • 16
    Thomson A. Dutasteride: an evidence-based review of its clinical impact in the treatment of benign prostatic hyperplasia. Core Evidence 2005; 1: 14356
  • 17
    Jenkins EP, Andersson S, Imperato-McGinley J, Wilson JD, Russell DW. Genetic and pharmacological evidence for more than one human steroid 5 alpha-reductase. J Clin Invest 1992; 89: 293300
  • 18
    Thigpen AE, Davis DL, Milatovich A et al. Molecular genetics of steroid 5 alpha-reductase 2 deficiency. J Clin Invest 1992; 90: 799809
  • 19
    Thigpen AE, Davis DL, Gautier T, Imperato-McGinley J, Russell DW. Brief report: the molecular basis of steroid 5 alpha-reductase deficiency in a large Dominican kindred. N Engl J Med 1992; 327: 12169
  • 20
    Rittmaster RS. 5alpha-reductase inhibitors in benign prostatic hyperplasia and prostate cancer risk reduction. Best Pract Res Clin Endocrinol Metab 2008; 22: 389402
  • 21
    GlaxoSmithKline. Avodart (Dutasteride) Soft Gel Capsules [Prescribing Information]. Research Triangle Park: GlaxoSmith Kline, 2008
  • 22
    Merck & Co. Inc. Proscar (Finasteride) Tablets [Prescribing Information]. Whitehouse Station: Merck & Co. Inc, 2010
  • 23
    Frye SV. Discovery and clinical development of dutasteride, a potent dual 5alpha-reductase inhibitor. Curr Top Med Chem 2006; 6: 40521
  • 24
    Wurzel R, Ray P, Major-Walker K, Shannon J, Rittmaster R. The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 2007; 10: 14954
  • 25
    McConnell JD, Roehrborn CG, Bautista OM et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349: 238798
  • 26
    Roehrborn CG, Siami P, Barkin J et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol 2010; 57: 12331
  • 27
    Kirby RS, Roehrborn C, Boyle P et al. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 2003; 61: 11926
  • 28
    Lepor H, Williford WO, Barry MJ et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med 1996; 335: 5339. Available at: http://www.nejm.org/oloi/full/10.1056/NEJM199608223350801