© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
expulsion rate was 30.4% (46 patients) in the control
group versus 52.2% (44 patients) in the sildosin group,
(
p = 0.036). The mean expulsion times were 21.00 days
in the control group versus 11.33 days in the sildosin
group, (p = 0.038). The mean number of times that
narcotic painmedications were necessarywas 1.7 times
in the control group versus 1.1 times in the sildosin
group, (p = 0.151).
Prostatitis
Silodosin (Rapaflo)
Chronic prostatitis, which has been proven to be
abacterial and which is commonly termed chronic
pelvic pain syndrome (CPPS), is a highly prevalent,
very difficult-to-treat disease.
13
Because LUTS
accompanies pain in CPPS, a number of studies
have looked at whether using alpha blockers might
ameliorate symptoms. Although the studies suggested
that these drugs might help, the findings have been
inconclusive and inconsistent.
14
Nickel et al recently reported results from a
randomized, double-blind, placebo-controlled trial
in which 151 patients with CPPS were randomized
to receive 4 mg silodosin, 8 mg silodosin, or placebo
once daily for 12 weeks.
15
The study endpoints were
the change in National Institutes of Health Chronic
Prostatitis Symptom Index total score and the impact
on urinary symptoms and quality of life. For all
parameters tested, the patient response with silodosin
was significantly better than with placebo, and there
was a marked improvement in quality of life. There
were no significant incremental improvements in
patients who received an 8 mg dose versus those
who received a 4 mg dose. Although the results
need to be confirmed in further studies, they are
very encouraging, and suggest a potential alternate
treatment approach for men with this very difficult-
to-treat disease.
Overactive bladder
Radomski and Barkin provide an overview of the
diagnosis and management of overactive bladder
(
OAB) elsewhere in this supplement.
16
OAB is a very
common disorder that has received a lot of attention in
the past few years. The primary treatment approach
is to use a medication that decreases the sensitivity
of the bladder and thereby improves the symptom of
urgency, which may or may not be accompanied by
incontinence and frequency.
The main class of drug for managing OAB has been
the anticholinergic/antimuscarinic medications. The
first significant agent for OAB was the anticholinergic
agent oxybutynin, and the gold standard therapy
for OAB is still immediate-release, oral oxybutynin.
The most common deficiency of these agents is not
their efficacy, but their side effect profiles, which
include increased risk of dry mouth and constipation,
aggravation of narrow-angle glaucoma, and a potential
impact on cognition in the elderly. Over the years,
because of bothersome side effects and a lack of
compliance due to the multiple doses per day required
with these agents, attempts have beenmade to develop
new, long-acting compounds.
Mirabegron
Mirabegron is a
β
3-
adrenoceptor agonist, the first in
a new class of agents developed for the treatment
of OAB. It has a direct impact on this condition by
causing relaxation of the detrusor muscle. In the
normal urination cycle, there are storage, voiding,
and post-micturition phases. By acting on the
detrusor muscle during the urine storage phase, the
drug increases bladder capacity and lengthens the
interval between voiding. It does not prevent bladder
contraction during the voiding phase.
17
The drug can
also reduce the sensation of urgency. Mirabegron,
given as once daily doses of 25 mg or 50 mg, has been
approved in Japan and the United States for treating
symptoms of OAB. A study of Mirabegron (Astellas)
was recently completed in Canada.
Fesoterodine (Toviaz)
Fesoterodine was recently approved byHealth Canada
and launched in the marketplace. It is an interesting
drug, because it is the metabolite of tolterodine
(
Detrol). It does not impact the liver, since under the
influence of serum esterases it is rapidly hydrolyzed to
its activemoiety, 5-hydroxymethyl tolterodine—which
is also the active metabolite of tolterodine. Tolterodine
has a maximum dosage of 4 mg/day due to concerns
about potential QT prolongation. In clinical trials,
fesoterodine did not prolong patients’ QT intervals,
and this added safety feature allows for dose titration
from the recommended starting dose of 4 mg daily to 8
mg daily, in certain patients.
18
This may provide better
efficacy; however, as with all drug dose titrations, the
clinician balances the efficacy response against the
potential for increased side effects.
Prostate cancer
The article by Shayegan
19
in this supplement provides
insight into the urologist’s approach for diagnosing and
managingdifferent stagesofprostatecancer. For invasive,
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Emerging therapies: what’s new is old and what’s old is new
