Transcript Critical Highlights

Clinical BPH and Its Management
A Comprehensive Slide Kit
Professor Kurt Dreikorn
Director, Department of Urology
Zentralkrankenhaus
Teaching Hospital of the University of Gottingen
Bremen, Germany
Mark Speakman, MD
Consultant Urologist
Musgrove Park Hospital
Taunton, UK
PSC 2001-W-11666-SS
This presentation is provided as a professional service
by Merck & Co., Inc. The views expressed herein
represent the independent opinions and experience
of the speakers and not necessarily those of
Merck & Co., Inc., or its related affiliates.
Any product mentioned in this presentation should
be used in accordance with the prescribing
information issued by the manufacturer.
PSC 2001-W-11666-SS
Definition, Pathophysiology,
and Epidemiology of Clinical BPH
Section I
PSC 2001-W-11666-SS
Definition of Terms
• LUTS
Lower-urinary-tract symptoms
• BPE
Benign prostatic enlargement
(macroscopic)
• BOO
Bladder-outlet obstruction
• BPH
Benign prostatic hyperplasia
(microscopic/histologic)
• BPO
Benign prostatic obstruction
(BOO caused by BPE)
• Clinical BPH
LUTS + BPE + BOO
PSC 2001-W-11666-SS
Slide I.1
Pathophysiology of Clinical BPH:
Overlapping but Independent Features
Enlarged
prostate
LUTS
BOO
Adapted from Nordling J et al. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:107-166.
PSC 2001-W-11666-SS
Slide I.2
Pathophysiology of Clinical BPH:
Conditions Potentially Leading to LUTS
Anoxia
High
nocturnal
diuresis
Aging
Obstruction
Bladder
Agerelated
diseases
Neurologic
diseases
Local
disease
LUTS
Adapted from Nordling J et al. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:107-166.
PSC 2001-W-11666-SS
Slide I.3
Pathophysiology of Clinical BPH:
Predictive Risk Factors
• Increasing age
• Prostatic enlargement
• Elevated prostate-specific antigen (PSA)
• Lower-urinary-tract symptoms (LUTS)
• Decreased urinary flow rate
PSC 2001-W-11666-SS
Slide I.4
% of men with prostate volume >50 ml
Natural History of BPH: Relationship Between
Symptoms and Prostate Volume
30
(N=2115)
Mild symptoms
Moderate/
severe symptoms
20
10
0
40–49
50–59
60–69
70–79
Age (years)
Adapted from Girman CJ et al J Urol 1995;153:1510-1515.
PSC 2001-W-11666-SS
Slide I.5
% of men with peak flow rate <10 ml/sec
Natural History of BPH: Relationship Between
Symptoms and Peak Urinary Flow
30
(N=2115)
Mild symptoms
Moderate/
severe symptoms
20
10
0
40–49
50–59
60–69
70–79
Age (years)
Adapted from Girman CJ et al J Urol 1995;153:1510-1515.
PSC 2001-W-11666-SS
Slide I.6
Natural History of BPH:
PSA Is a Powerful Risk Factor for Clinical BPH
5
(N=1709)
4.4
Odds ratio
4
3
2
1
1.8
1.9
0.08–0.10
0.11–0.17
1
0
0.0–0.07
0.18–2.43
Free PSA value
p<0.00001 for trend across odds ratios
Free PSA values adjusted for age and total PSA
Adapted from Meigs JB et al J Clin Epidemiol 2001;54(9):935-944.
PSC 2001-W-11666-SS
Slide I.7
Pathophysiology of Clinical BPH:
The Risk of AUR Increases with Increasing
Prostate Volume (community-based data)
3.5
3
Relative risk of AUR
3
2.5
2
1.5
1
1
0.5
0
30
>30
Baseline prostate volume (ml)
Adapted from Jacobsen SJ et al J Urol 1997;158:481-487.
PSC 2001-W-11666-SS
Slide I.8
Pathophysiology of Clinical BPH:
The Risk of TURP Increases with Increasing
Prostate Volume (community-based data)
10
(N=2115)
9.2
Relative risk of TURP
8
6
4
2
1
0
30
>30
Baseline prostate volume (ml)
Adapted from Jacobsen SJ et al J Urol 1999;162:1301-1306.
PSC 2001-W-11666-SS
Slide I.9
Definition, Pathophysiology, and Epidemiology
of Clinical BPH: Summary
• Clinical BPH is a multifactorial disease composed mainly of
prostatic enlargement, LUTS, and BOO
• Age, prostatic enlargement, elevated PSA, LUTS, and
decreased urinary flow rate are major independent predictive
risk factors
– Elevated PSA levels powerfully predict clinical BPH and
subsequent outcomes
• Prostate volume correlates with BOO, severity of symptoms,
and risk of serious outcomes
PSC 2001-W-11666-SS
Slide I.10
Consequences of BPH
Section II
PSC 2001-W-11666-SS
Complications of Untreated
Clinical BPH
• Acute urinary retention
• Urinary tract infection
• Bladder calculi
• Bladder damage
• Renal impairment
• Hematuria
PSC 2001-W-11666-SS
Slide II.1
Incidence of Serious Clinical Outcomes in
Untreated Patients with BPH vs. Other Diseases
Condition
Clinical Outcome
Incidence (%)*
Osteoporosis
Vertebral fracture
Hip fracture
1.5
18
Atherosclerosis
Fatal/nonfatal MI
2.1
Superficial bladder cancer
Recurrence
30–88
Kidney stones
Recurrence
2–47
AUR
Surgery
7
10
BPH
*Annual incidence or rate per person-years
Adapted from Roehrborn CG et al Urology 2000;56:9-18. McConnell JD et al N Engl J Med 1998; 338(9):557-563.
PSC 2001-W-11666-SS
Slide II.2
Impact of Clinical BPH on
the Patient’s Quality of Life
Health-related quality-of-life score
10
Prostate 40 ml
Prostate >40 ml
(n=458)
9.0
8
6
6.1
5.6
4
3.6
3.1
2.3
2
0
Symptom score
(p<0.0001)
Bother score
(p<0.005)
Activity score
(NS)
Higher scores reflect worse status.
Adapted from Girman CJ et al Eur Urol 1999;35(4):277-284.
PSC 2001-W-11666-SS
Slide II.3
Impact of Clinical BPH on
the Spouse’s Quality of Life
80
(n=90)
71
70
66
66
% of spouses
60
50
47
40
30
20
10
0
Adverse
effects on
social life
Adverse
impact on
sex life
Worry about
prostate cancer
Worry about
partner’s need
for surgery
Adapted from Sells H et al Br J Urol Int 2000;85:440-445.
PSC 2001-W-11666-SS
Slide II.4
Consequences of Untreated Clinical BPH:
Summary
• Serious clinical outcomes
– AUR
– BPH-related surgery
• Adverse impact on quality of life
– For patients
– For spouses
PSC 2001-W-11666-SS
Slide II.5
Regulation of Prostate Growth
Section III
PSC 2001-W-11666-SS
Regulation of Prostate Growth:
Intrinsic and Extrinsic Factors
Extrinsic factors
Testicular
• Androgens
• Estrogens
• Nonandrogenic
Intrinsic factors
(prostate)
Nontesticular
• Endocrine organs
• Neurotransmitters
• Immunologic
Epithelium
• Luminal
• Basal
• Neuroendocrine
Stroma
• Fibroblast
• Smooth muscle
• Extracellular matrix
Urethra
• Urine
• Testis-epididymal
fluid
Genetic
• Homeobox genes
• Hereditary
diseases
Environmental
• Dietary
• Micro-organisms
(immune response)
Extrinsic factors
Adapted from Lee C et al. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:79-106.
PSC 2001-W-11666-SS
Slide III.1
Regulation of Prostate Growth:
Role of Androgens
• DHT is the principal androgen responsible for prostatic growth
and BPH
• 5-reductase mediates the conversion of testosterone to DHT
OH
OH
5-reductase
O
O
H
Testosterone
Dihydrotestosterone
Adapted from Bartsch G et al Eur Urol 2000;37(4):367-380.
PSC 2001-W-11666-SS
Slide III.2
Regulation of Prostate Growth:
Role of 5-Reductase
• Inherited 5-reductase deficiency results in male
pseudohermaphroditism, characterized by
– Markedly reduced DHT and normal testosterone levels
– Lack of prostatic development and/or enlargement (BPH)
• 5-reductase plays a key role in both normal and abnormal
prostate growth
In the 1980s, inhibitors that selectively blocked the action
of 5-reductase were synthesized for the treatment of
symptomatic BPH.
PSC 2001-W-11666-SS
Slide III.3
Relative Roles of Type I and
Type II 5-reductase
Tissues in which type I and type II 5-reductase are predominant
Type I
Skin (sebaceous
glands)
Type II
Hair follicles
Liver
Seminal vesicles
Liver
Prostate gland
Epididymis
Adrenal
glands
PSC 2001-W-11666-SS
Internal/external
genital tissues
Slide III.4
Regulation of Prostate Growth:
Summary
• DHT is a key to the regulation of prostatic growth and BPH
• 5-reductase mediates the conversion of testosterone to DHT
• 5-reductase plays a key role in normal and abnormal
prostate growth
• 5-reductase has two isoenzymes, type I and type II
– Type II predominates in the prostate and other genital
tissues
• Agents that selectively block the action of 5-reductase have
been synthesized for the treatment of symptomatic BPH
– Finasteride is a selective inhibitor of type II 5-reductase
PSC 2001-W-11666-SS
Slide III.5
Management of BPH
Section IV
PSC 2001-W-11666-SS
Diagnosis of Clinical BPH:
International Recommendations
Assessment
Quantification of symptoms–IPSS
Quantification of symptoms—bother score
Digital rectal examination
Urinalysis
PSA measurement
Voiding diary (frequency-volume charts)
Urinary flow-rate recording
Postvoid residual urine volume studies
Pressure-flow studies
Prostate imaging (TRUS)
Upper-urinary-tract imaging (US or IVU)
Lower-urinary-tract endoscopy
Serum creatinine measurement
ICBPH Guidelines
Recommended
Recommended
Recommended
Recommended
Recommended
Recommended
Optional
Optional
Optional
Optional
Optional
Optional
Not recommended
Adapted from Fifth International Consultation 2001 on BPH. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication,
2001:519-535.
PSC 2001-W-11666-SS
Slide IV.1
Treatment of Clinical BPH:
International Recommendations
Findings
Recommendation
Minimal/not bothersome LUTS
No absolute indication for surgery*
Watchful waiting
Bothersome LUTS
Enlarged prostate
No absolute indication for surgery*
Watchful waiting
Medical treatment
• Finasteride
• Alpha blocker
Interventional treatment
Bothersome LUTS
Normal prostate
No absolute indication for surgery*
Watchful waiting
Medical treatment
• Alpha blocker
Interventional treatment
Bothersome LUTS
Normal or enlarged prostate
Absolute indication for surgery*
Surgery
*Absolute indications for surgery include urinary retention; significant gross hematuria refractory to finasteride treatment; renal failure,
bladder stones, or recurrent urinary tract infections due to BOO; or large bladder diverticulum.
Adapted from Fifth International Consultation 2001 on BPH. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication,
2001:519-535; De la Rosette JJMCH et al Eur Urol 2001;40:256-263.
PSC 2001-W-11666-SS
Slide IV.2
Treatment of Clinical BPH:
Objectives
ICBPH guidelines
• Short term
– Improve symptoms
• Long term
– Slow disease progression
– Minimize adverse effects of treatment
– Preserve quality of life
Adapted from Fifth International Consultation 2001 on BPH. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication,
2001:519-535.
PSC 2001-W-11666-SS
Slide IV.3
Alpha Blockers:
Mechanism of Action
• Improve urinary flow and reduce BOO and LUTS
• Do not affect prostate enlargement
• Established mechanisms
– Blockade of sympathetic activity
– Relaxation of prostatic and bladder-neck smooth
muscle
– No effect on disease progression
PSC 2001-W-11666-SS
Slide IV.4
5-Reductase Enzyme Inhibitors:
Mechanism of Action of PROSCAR™
Testosterone
Type II 5-reductase
DHT
Conversion of Testosterone to Dihydrotestosterone
PROSCAR
Testosterone
Type II 5-reductase
DHT
Enzyme Inhibition
• Significantly reduces serum and intraprostatic DHT
• Treats the underlying cause of BPH
PROSCAR (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.
PSC 2001-W-11666-SS
Slide IV.5
Management of Clinical BPH:
Summary
• International guidelines for the management of clinical
BPH recommend
– Diagnostic tests to characterize disease severity and rule
out other disorders
– Treatment to relieve symptoms and prevent complications
• Alpha blockers relieve BPH symptoms primarily by relaxing
smooth muscle
• PROSCAR™ relieves BPH symptoms primarily by reducing
prostate volume
• PROSCAR slows the progression of BPH
PSC 2001-W-11666-SS
Slide IV.6
Time-Tested Clinical Benefits
of PROSCAR™
Section V
PSC 2001-W-11666-SS
Evidence-Based Medicine:
Proven Treatment for Clinical BPH
• Evidence-based medicine is based on results of
clinical research.
• Drugs in the same therapeutic class may exert different
pharmacologic effects.
• Independent clinical studies must establish each drug’s
efficacy, safety, and effect on outcomes.
• Outcome studies with drugs for clinical BPH should
evaluate the effects of therapy on AUR and BPH-related
surgery.
PSC 2001-W-11666-SS
Slide V.1
Acute Urinary Retention in
Clinical BPH Treatment Trials
Patient population (no.)
Study duration
Average prostate size
Follow-up of discontinued
patients
No. of AUR events during trial
Predicted no. of AUR events for
patients after discontinuation
Total no. of AUR events
(actual and predicted)
Trials with
PROSCAR™
Trials with
Alpha Blockers
3000–4222
2–4 years
41–55 ml
Yes
518–2084
6 months–1 year
41 ml
No
72–81
5–8
4–24
1–10
80–86
4–34
• PLESS was the only study to provide spontaneous AUR data for the active
treatment versus post-treatment follow-up.
Adapted from Roehrborn CG Urology 2002;59:811-815.
PSC 2001-W-11666-SS
Slide V.2
PROSCAR™:
Treatment Goals
PROSCAR has been proved effective in the treatment of
clinical BPH in men with an enlarged prostate.
• Improves symptoms
• Reduces risk of AUR
• Reduces risk of BPH-related surgery
• Slows disease progression
PSC 2001-W-11666-SS
Slide V.3
PROSCAR™:
Durable Efficacy in Long-Term Trials
Study
Duration
(years)
North American
1
SCARP
2
PROSPECT
2
PROWESS
2
PLESS
4
North American Extension*
Scandinavian Open Extension*
Long-Term Improvement
Symptoms Prostate Volume Urinary Flow















Maintained
Maintained
Maintained
Maintained
Maintained
Maintained
 = significant improvement from baseline vs. placebo (p0.05);
SCARP = Scandinavian Study of Reduction of the Prostate; PROSPECT = Proscar Safety Plus Efficacy Canadian Two-Year Study;
PROWESS = Proscar Worldwide Efficacy and Safety Study; PLESS = Proscar Long-term Efficacy and Safety Study
*Benefits achieved during double-blind therapy were maintained in extensions.
PSC 2001-W-11666-SS
Slide V.4
Effects of PROSCAR™ on the Natural History
of Clinical BPH: Reduced Risk of AUR
Probability of AUR
15
10
57%
Placebo
risk
reduction
p<0.001
5
PROSCAR
0
0
1
2
3
4
Years
Placebo
No. of AURs
No. at risk
36
1503
25
1454
20
1398
18
1347
PROSCAR
No. of AURs
No. at risk
14
1513
11
1487
7
1449
10
1421
p<0.001 at 4 years PROSCAR vs. placebo
Adapted from McConnell JD et al N Engl J Med 1998;338(9):557-563.
PSC 2001-W-11666-SS
Slide V.5
Effects of PROSCAR™ on the Natural History
of Clinical BPH: Reduced Risk of Surgery
Probability of surgery
15
Placebo
55%
10
risk
reduction
p<0.001
5
PROSCAR
0
0
1
2
3
4
Years
No. of surgeries
No. at risk
37
1503
52
1454
32
1374
31
1314
PROSCAR No. of surgeries
No. at risk
18
1513
22
1483
9
1438
20
1410
Placebo
p<0.001 at 4 years, PROSCAR vs. placebo
Adapted from McConnell JD et al N Engl J Med 1998;338(9):557-563.
PSC 2001-W-11666-SS
Slide V.6
Effect of PROSCAR™ on the Natural
History of BPH: Relative Risk Reductions
vs. Interventions in Other Diseases
Condition
Osteoporosis
Outcome
Intervention
Vertebral fracture
Alendronate
Hip fracture
Alendronate
Atherosclerosis
PTCA or CABG
Statins
Fatal/nonfatal MI
Statins
Epilepsy
Seizures
Anticonvulsants
Superficial bladder cancer
Recurrence
BCG + surgery
Kidney stones
Recurrence
Pharmacotherapy
BPH
AUR
PROSCAR
Surgery
PROSCAR
Risk
Reduction (%)
44–47
21–51
17–37
25–40
38–87
31–80
63–80
57
55
PTCA = percutaneous transluminal coronary angioplasty; CABG = coronary artery bypass graft; BCG = bacillus Calmette-Guérin
Adapted from Roehrborn CG et al Urology 2000;56:9-18. McConnell et al N Eng J Med 1998;338(9):557-563.
PSC 2001-W-11666-SS
Slide V.7
PSA and PROSCAR™
In PLESS, PROSCAR did not mask prostate cancer
detected by PSA
• Predictably reduces PSA by 50% in men with BPH
• Multiplication of PSA values by 2 in men treated
for 6 months preserves predictive value of PSA
measurements
PSC 2001-W-11666-SS
Slide V.8
Time-Tested Clinical Benefits
of PROSCAR™: Summary
• Evidence-based medicine calls for clinical studies of individual
drugs that investigate efficacy and disease outcomes.
• Outcomes studies with drugs for clinical BPH should evaluate
effects on AUR and BPH-related surgery.
• Multicenter, double-blind, placebo-controlled trials of up to
6 years’ duration have established the effects of PROSCAR:
– Durable improvements in symptoms, prostate volume,
and maximum urinary flow (p0.05) over 1 to 4 years
vs. placebo
– Significant reductions in the risk of AUR and BPH-related
surgery (p<0.001) at 4 years vs. placebo in PLESS
• No other therapy—including alpha blockers—proven to
reduce AUR
PSC 2001-W-11666-SS
Slide V.9
New Data on the Long-Term Efficacy
and Tolerability of PROSCAR™
Section VI
PSC 2001-W-11666-SS
Long-Term Experience
with PROSCAR™
• Sustained improvements over 7 years of therapy
– Reductions in symptom scores
– Sustained reductions in prostate volume
25% reduction at year 7
– Sustained increases in urinary flow
2.5 ml/sec increase at year 7
• Consistent safety and tolerability profile over 8 years
of therapy
Data on file, MSD.
PSC 2001-W-11666-SS
Slide VI.1
Younger men
(<65 years)
20
18
16
14
12
10
8
6
4
2
0
Older men
(65 years)
Placebo
(n=774)
51% risk
reduction
(p<0.001)
PROSCAR
(n=786)
0
1
2
3
4
Year
Four-year probability of AUR
and/or needing surgery
Four-year probability of AUR
and/or needing surgery
Efficacy of PROSCAR™ in Younger vs. Older
Men with Clinical BPH (PLESS Subanalysis)
20
18
16
14
12
10
8
6
4
2
0
Placebo
(n=742)
51% risk
reduction
(p<0.001)
PROSCAR
(n=738)
0
1
2
3
4
Year
• PROSCAR significantly reduced the incidence of AUR and BPH-related
surgery in younger and older patients at 4 years (p<0.001).
Adapted from Kaplan SA et al Urology 2001;57(6):1073-1077.
PSC 2001-W-11666-SS
Slide VI.2
Rapid and Sustained Reduction in the Risk
of Long-Term Outcomes with PROSCAR™
Double-blind study
Open-label extension
Placebo  PROSCAR 5 mg (n=858)
PROSCAR 5 mg  PROSCAR 5 mg (n=979)
Placebo (n=1503)
PROSCAR 5 mg (n=1513)
Yearly % of AUR and/or
BPH-related surgery
5
4
4.4
3.7
3.3
3.0
3
2
1.9
2.1
2.0
1.4 1.3
1.0
1.0
1
0.7
0
1
2
3
4
5
6
Study year
n values indicate number of patients completing each trial phase
Adapted from Roehrborn CG et al. Poster 419.
PSC 2001-W-11666-SS
Slide VI.3
PROSCAR™ Significantly Reduced Bother Over
Long-Term Therapy (4 Years) (PLESS Substudy)
Mean (±SE) change in
bother score from baseline
0
Overall
bother score*,**
By baseline PSA tertile (ng/ml)
PSA: 0–12
PSA: 0–1.3
Placebo
(n=1503)
PSA: 3.3–12
PSA: 1.4–3.2
PROSCAR
5 mg
(n=1513)
–1
–2
–3
–4
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
Year of follow-up
*p<0.05 PROSCAR vs. placebo at every time point after 4 months to 1 year and p<0.001 PROSCAR vs. placebo every 4 months, years 1 to 4
**Significant improvement vs. baseline with PROSCAR and placebo at 4 years, p<0.001
PSA = prostate-specific antigen
Adapted from Bruskewitz R et al Urology 1999;54:670-678.
PSC 2001-W-11666-SS
Slide VI.4
PROSCAR™ Had No Effect on Bone Mineral
Density (BMD) (PLESS Substudy)
1.15
1.14
1.14
1.13
BMD (g/cm2)
1.13
1.12
PROSCAR (n=63)
Placebo (n=54)
1.12
1.11
1.10
1.10
1.09
1.08
Baseline
End of study
p = NS between treatments
Adapted from Matsumoto AM et al J Urol 2002;167:2105-2108.
PSC 2001-W-11666-SS
Slide VI.5
New Data on the Long-Term Efficacy and
Tolerability of PROSCAR™: Summary
• PROSCAR maintains clinical improvements over long-term therapy
– Sustained reductions in symptom scores and prostate volume
and increases in urinary flow over 7 years
– Durable effects up to 10 years
– Similar effects in older vs. younger men
– Reductions in risk of outcomes maintained over 6 years
– Significant reductions in bother due to BPH symptoms at 4 years
(p<0.001 vs. placebo)
• PROSCAR is well tolerated over long-term therapy
– Consistent safety/tolerability profile through year 7
– No effect on BMD
PSC 2001-W-11666-SS
Slide VI.6
The Patient-Physician
Connection
Section VII
PSC 2001-W-11666-SS
Patient Satisfaction Is Important in
the Treatment of Clinical BPH
• Treatment selection in BPH should take into account
– Patient’s perception of the impact of BPH on
quality of life
– Patient’s ability to deal with bother caused
by symptoms
– Patient’s attitudes toward risk of possible
complications
PSC 2001-W-11666-SS
Slide VII.1
The Physician’s Role
in Patient Education
• Physicians should involve patients with BPH in
the choice of therapy
• Patient education should include discussions of
– The natural history of BPH (including potential
for serious complications)
– Benefits, risks, and costs of alternative approaches
PSC 2001-W-11666-SS
Slide VII.2
Combination Therapy
for Clinical BPH
Section VIII
PSC 2001-W-11666-SS
Combined Therapy with PROSCAR™ and
an Alpha Blocker (terazosin) for Clinical BPH
20
PROSCAR 5 mg/day
Terazosin titrated to 5 mg
Combination
18
Mean IPSS
16
14
12
10
8
0
2
4
6
8
10
12
Time (months)
p<0.05 PROSCAR + terazosin vs. either agent used alone at 12 months
Adapted from Savage SJ et al Can J Urol 1998;5(3):578-584.
PSC 2001-W-11666-SS
Slide VIII.1
Discontinuation of Alpha Blockade After
Combined Therapy with PROSCAR™ and
an Alpha Blocker (doxazosin) for BPH
Success rates after discontinuation
(% of patients)
100
80
Doxazosin 2 mg (n=25)
Doxazosin 4 mg (n=20)
Doxazosin 8 mg (n=15)
84
84
85 87
80
73
60
48
40
20
45
40
20
15 13
0
3 months
6 months
9 months
12 months
Time after discontinuation
Adapted from Baldwin KC et al Urology 2001;58(2):203-209.
PSC 2001-W-11666-SS
Slide VIII.2
Combined Therapy with PROSCAR™ and
an Alpha Blocker for Clinical BPH: Summary
• Enhanced relief of symptoms
• After withdrawal of alpha blocker
– Satisfaction (success) rates maintained
87% after 12 months in one study
PSC 2001-W-11666-SS
Slide VIII.3
Other Emerging Uses
of PROSCAR™
Section IX
PSC 2001-W-11666-SS
PROSCAR™ Decreases
the Risk of Hematuria
70
Control (n=27)
PROSCAR (n=28)
63
60
% of men
50
40
30
26
20
14
10
0
0
Hematuria*
at 1 year
*p<0.05 between groups
PROSCAR is not indicated for treatment of BPH-related hematuria.
Hematuria
requiring surgery
at 1 year
Adapted from Foley SJ et al J Urol 2000;163:496-498.
PSC 2001-W-11666-SS
Slide IX.1
Pretreatment with PROSCAR™ Decreases
Perioperative Bleeding Associated with TURP*
% of patients with bleeding
40
35
Placebo
PROSCAR
36.8
30
25
20
15
14
8.3
10
4
5
0
(n=50)
(n=25)
Total group
0
0
(n=31)
(n=13)
<30 g resected
(n=19)
(n=12)
30 g resected
*PROSCAR was given 2–4 months before TURP.
PROSCAR is not indicated for pretreatment before prostate surgery.
Adapted from Hagerty JA et al Urology 2000;55:684-689.
PSC 2001-W-11666-SS
Slide IX.2
Other Emerging Uses
of PROSCAR™: Summary
• Extended benefits of PROSCAR in men with BPH
– Reduced risk of hematuria and hematuria-related
surgery
– Improved outcomes when used prior to BPH-related
surgery
• PROSCAR is not currently indicated for these uses.
PROSCAR is not currently indicated for these uses.
PSC 2001-W-11666-SS
Slide IX.3
Summary
Section X
PSC 2001-W-11666-SS
Overall Summary
and Conclusions
• BPH, a multifactorial disorder characterized by an enlarged
prostate, LUTS, and BOO, can lead to serious clinical outcomes
(AUR and BPH-related surgery).
• PROSCAR™ is a competitive and specific inhibitor of type II
5-reductase, which mediates the conversion of testosterone
to DHT.
• PROSCAR reduces BPH symptoms and prostate size,
improves urinary flow, and decreases the risk of AUR and
BPH-related surgery.
• PROSCAR slows the progression of BPH.
• The clinical effects of PROSCAR have been established in clinical
trials of up to 7 years’ duration.
PSC 2001-W-11666-SS
Slide X.1
Bibliography
• See Notes page
PSC 2001-W-11666-SS
Bibliography (cont’d)
• See Notes page
PSC 2001-W-11666-SS
Clinical BPH and Its Management
A Comprehensive Slide Kit
Before prescribing any of the products mentioned
in this slide presentation, please consult the manufacturer’s
prescribing information.
Copyright © 2002 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved.
7-03 PSC 2001-W-11666-SS
Printed in USA
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PSC 2001-W-11666-SS