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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
cases where well-informed patients wish to remain
sexually active by avoiding LHRHA therapy.
74
Liver
function tests must be monitored periodically in those
taking antiandrogens as they are metabolized by the
cytochrome P450 system in the liver.
Castrate resistant prostate cancer
There have been several developments in the treatment
of advanced prostate cancer over the last year that
warrant further discussion. Castrate resistant prostate
cancer (CRPC) is the cause of death in most men with
advanced disease. The above mentioned androgen
ablation therapies are used as the standard of care for
metastatic prostate cancer. However, many patients
develop CRPC defined as progressive disease despite
castrate levels of serum testosterone (i.e
.
< 50 ng/dL
or < 1.73 nmol/L).
75
This advanced disease state is
now termed CRPC or metastatic CRPC (mCRPC). The
historic term of “hormone refractory prostate cancer”
is now considered to be a misnomer since it has been
recognized that there is actually increased production
of intra-tumoral androgens in patients with CRPC.
Prior to 2004, chemotherapy for CRPC was limited
to palliative care with mitoxantrone [Novantrone].
Two trials in 2004 established docetaxel [Taxotere] as
the standard of care for CRPC.
76,77
In 2010 cabazitaxel
[Jevtana (US only)], a novel taxane, was approved
for the treatment of patients with mCRPC who failed
docetaxel-based chemotherapy, Table 8b.
Sipuleucel-T [Provenge (US only)] is a first of its
kind therapeutic cancer vaccine that uses patients’
own immune cells to stimulate an immune response
against prostate cancer cells, Table 8b.
78
Sipuleucel-T
is indicated for the treatment of patients with mCRPC
with either minimal or no symptoms. Studies showed
a significant improvement in median overall survival
with sipuleucel-T compared with placebo of about 4
months.
78
Administration requires a series of three
leukophoresis procedures as well as processing of the
cells at a production facility where the patient’s own
dendritic cells are modified for subsequent reinfusion.
Conclusion
With the increased prevalence of many common
urologic diseases as the average age of the adult
population in North America shifts upward, the
primary care physician will continue to play an
increasing role in the treatment of patients with both
malignant and benign urologic conditions. Treatment
of sBPH, ED, hypogonadism, OAB, and prostate
cancer require frequent interaction and management
discussions between the urologist and the patient’s
general practitioner to maximize therapeutic efficacy
and limit medical toxicity. With a basic understanding
of urologic pathophysiology as well as pharmacologic
mechanisms of action, dosing regimens and side effect
profiles of common urologicmedical therapies, primary
care physicians are better armed to engage their
patients in a discussion regarding treatment options
for a number of urologic disease processes.
TABLE 8c.
Antiandrogen hormonal therapy for prostate cancer
Name (Brand)
Class
Administration
Notes
Flutamide
Nonsteroidal
250 mg PO every 8 hours
Follow LFTs
(Euflex [Canada],
antiandrogen
w/LHRH analog
Eulexin [US] )
Nilutamide
Nonsteroidal
Start: 300 mg PO daily
Follow chest x-ray
(Anandron [Canada])
antiandrogen
x30 days, and then consider
Follow LFTs
(Nilandron [US])
150 mg PO daily
baseline PFTs;
w/LHRH analog or orchiectomy
Bicalutamide
Nonsteroidal
50 mg PO daily
Follow LFTs
(Casodex)
antiandrogen
w/ LHRH analog
Cyproterone acetate
Steroidal
100 mg-300 mg PO daily,
Follow LFTs;
(Androcur, Androcur
antiandrogen
divided into 2-3 doses (after meals)
not available in US
Depot [Canada, not US]
300 mg IM weekly or
300 mg IM q2weeks (if orchiectomized)
LFTs = liver function tests
36
LIU ET AL.