© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
Kapoor
14
if a patient’s PSA is 8 ng/mL prior to the initiation of
a 5-ARI, then after 4 to 6 months of therapy, the PSA
should be in the 4 ng/mL range. While continuing
on 5-ARI the PSAvalue should stay around this level.
If the PSA rises on 5-ARI then a referral to a urologist
is mandatory to exclude the development of new
prostate cancer. While the patient is receiving a 5-ARI,
the prostate should be checked with an annual DRE.
Controversy still exists about the increased risk
of developing high grade prostate cancer in patients
taking a 5-ARI such as finasteride or dutasteride. Health
Canada and the US Food and Drug Administration
(
FDA) issued a label change for finasteride and
dutasteride to include new safety information about
the possible increased risk of being diagnosedwith high
grade prostate cancer while on these agents, based on
analysis of data from the Prostate Cancer Prevention
Trial (PCPT)
26
and the Reduction by Dutasteride of
Prostate Cancer Events (REDUCE) trial.
27
Some experts
have suggested that the increased risk of high grade
prostate cancer may be an artifact resulting from the
interpretation of prostate biopsies in these studies.
Current recommendations are to exclude prostate
cancer in BPH patients (based on PSA and DRE) prior
to initiating 5-alpha reductase inhibitors for BPH.
Combination therapy
Studies have shown the benefit of combination therapy
with 5-ARIs and alpha blockers.
25
The benefit is
greatest in patients with large prostates, where the
5-
ARI shrinks the prostate and the alpha blocker
relaxes the smooth muscle of the prostate providing
combination benefits. For patients with smaller
prostates, alpha blockers alone may be sufficient to
alleviate urinary symptoms. Two landmark studies
examined combination therapy for BPH:
MTOPS:
The Medical Therapy of Prostate Symptoms
(
MTOPS) study was a landmark trial comparing
monotherapy with an alpha blocker (doxazosin) or
a 5-ARI (finasteride [Proscar]) versus combination
therapy (doxazosin and finasteride) for BPH.
28
This
study randomized patients into four treatment
groups: an alpha blocker (doxazosin) alone, a 5-ARI
(
finasteride) alone, combination therapy, and placebo.
28
Combination therapy provided the most effective
increase in flow rate, improvement in symptom
scores, reduction in risk of acute urinary retention,
and reduction in the need for surgery. Prostate volume
decreased in patients who received finasteride alone,
and in patients who were treated with finasteride plus
an alpha blocker. Patients who were treated with an
alpha blocker alone or with placebo had an increased
prostate volume over time, and they did not have
a reduced need for future BPH-related surgery or a
reduced risk of developing acute urinary retention.
CombAT:
The Combination ofAvodart and Tamsulosin
(
CombAT) study was designed to examine whether
the combination of dutasteride and tamsulosin was
more effective than monotherapy alone for improving
symptoms for men who had BPH, or to prevent the
progression of BPH. The 4 year results and the 2 year
results showed that there was an improvement in
the quality of life and an improvement in symptom
scores in men with proven, enlarged prostates that
were larger than 30 cc.
There was also a 66% relative
risk reduction in the onset of acute urinary retention
or the need for surgery in the combination arm
compared to the active treatment with tamsulosin.
29
With improvement on combination therapy, in most
cases men were able to stop taking the alpha blocker
after 6 to 9 months.
29
After stopping the alpha blocker
most of the men were still able to maintain a fairly
good, symptom-free response. Jalyn, a single-capsule
combination of dutasteride 0.5 mg and tamsulosin 0.4
mg was approved for use in men with symptomatic
BPHbased on the study results from the CombAT trial.
TABLE 2.
5-
alpha reductase inhibitor (5-ARI) medications for symptomatic benign prostatic hyperplasia (sBPH)
Name (Brand name)
Dose
Half-life
Mechanism
Side effects/Notes
Finasteride
5
mg daily
6-8
hours
Inhibits type II
Decreased libido; sexual
(
Proscar)
5-
AR*
dysfunction; gynecomastia
Dutasteride
0.5
mg daily
3-5
weeks
Inhibits types I
Same as above
(
Avodart)
and II 5-AR*
Dutasteride/
0.5
mg dutasteride & 9-13 hours
Combination
See dutasteride and
Tamsulosin
0.4
mg tamsulosin
(
tamsulosin), 5-ARI and
tamsulosin
(
Jalyn)
combination daily
3-5
weeks
alpha blocker
(
dutasteride)
*
5-
AR = 5-alpha reductase
