Basic HTML Version
© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
27
Recently, there have been several publications and
studies analyzing the use of 5-ARIs as chemoprevention
for prostate cancer. TheProstateCancer PreventionTrial
(PCPT) with finasteride demonstrated a 25% relative
risk reduction in the incidence of prostate cancer over 7
years but suggested an increase in the detection of high
risk disease compared to placebo.
16
More recently, the
REDUCE (REduction by DUtsteride of prostate Cancer
Events) trial showed results similar to the PCPT with
prostate cancer risk reduction of approximately 23%
over a 4 year period with the 5-ARI dutasteride.
17,18
While these results are promising, neither 5-ARI agent
has been approved by Health Canada or in the United
States for chemoprevention of prostate cancer. Amajor
meeting of the US FDA Oncology Drugs Advisory
Committee (ODAC) in December 2010 rejected the
use of the entire class of 5-ARIs for prostate cancer
risk reduction (http://www.fda.gov/downloads/
AdvisoryCommittees/CommitteesMeetingMaterials/
Drugs/OncologicDrugsAdvisoryCommi t tee/
UCM239355.pdf).
Alpha blocker and 5-ARI combination therapy
TheMedical Therapy of Prostatic Symptoms (MTOPS)
trial was the first to demonstrate that combination
therapywith an alpha blocker (doxazosin) and a 5-ARI
(finasteride) was superior to either alone in preventing
sBPH progression.
19
Specifically, the incidence of
urinary retention and need for surgical therapy
was reduced in those taking combination therapy.
Similarly the CombAT (Combination of Avodart and
Tamusloin) trial published in 2008 demonstrated a
greater improvement in urinary symptoms in men
with BPE on combination therapy compared to either
TABLE 3.
5-alpha reductase inhibitor (5-ARI) medications for symptomatic benign prostatic hyperplasia (sBPH)
Name (Brand)
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 [US, not Canada]) combination daily
3-5 weeks
alpha blocker
(dutasteride)
*
5-AR = 5-alpha reductase
TABLE 2.
Current recommendations concerning alpha blockers for symptomatic BPH and Intraoperative
Floppy Iris Syndrome (IFIS)
American Society of Cataract and Refractive Surgery (ASCRS) and the American Academy of Ophthalmology
(AAO) issued the following recommendations in June 2009*
All alpha blockers can cause IFIS, but several studies suggest that IFIS is more likely to occur with the “selective”
alpha blocker such as tamsulosin compared to the other “non-selective” alpha blockers. There are no data yet on
IFIS with silodosin, but it is pharmacologically “selective” for the iris and prostate tissue similar to tamsulosin.
• Patients taking alpha blockers should inform their ophthalmologist before undergoing eye surgery.
• Prior to being started on an alpha blocker, patients with cataracts should be informed that alpha blockers
may place them at increased risk for surgical complications and should consider having surgery done before
initiating alpha blocker therapy.
• Many ophthalmologists recommend ophthalmologic evaluation in patients with a history of cataracts or
decreased vision prior to starting tamsulosin.
• Discontinuation of tamsulosin prior to cataract surgery did not reduce the severity of IFIS in a prospective trial.
• Ophthalmologic surgeons may be able to modify surgical techniques in at-risk patients.
*Available on line at http://www.ascrs.org/press_releases/IFIS-Press-Release.cfm
Pharmacology for common urologic diseases: 2011 review for the primary care physician