© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
33
PSA implications and medical management of prostate cancer for the primary care physician
impairment, and cardiovascular compromise.
23
Some
adverse effects of hormonal therapiesmay bemitigated
by intermittent and judicious use of these agents and
by careful patient monitoring.
Chemotherapy
Castrate resistant prostate cancer (CRPC) is defined
as disease progression despite having achieved an
acceptable castrate testosterone level, and it may
present as either a continuous rise in serum PSA
levels, progression of pre-existing disease, and/or the
appearance of new metastases.
23
Patients with CRPC
and macroscopic metastatic disease are considered to
be candidates for systemic chemotherapy. Current
chemotherapeutic options are rapidly expanding
beyond docetaxel (Taxotere).
Cabazitaxel (Jevtana), a novel taxane, in combination
with prednisone, is approved for the treatment of
patients with metastatic CRPC who failed docetaxel-
based chemotherapy.
24
Abiraterone [Zytiga] is a new
oral androgen biosynthesis inhibitor indicated for use
in combination with prednisone for the treatment of
metastatic prostate cancer (CRPC) in patients who have
received prior chemotherapy containing docetaxel.
25
Abiraterone inhibits the CYP17 enzyme which is
required for androgen biosynthesis in testicular, adrenal
andprostatic tumor tissues, reducing serumtestosterone
and other androgens to levels lower than that achieved
with LHRH agonists alone or orchiectomy.
25
A recent
clinical trial concluded that abiraterone prolongs overall
survival among patients with metastatic prostate
cancer who previously received chemotherapy with
docetaxel.
26
Enzalutamide (Xtandi) is an oral androgen
receptor inhibitor recently approved in theUnited States
for the treatment of patients withmetastatic CRPCwho
have previously received docetaxel, and may be given
with or without prednisone.
27
See Table 3 for a list of
chemotherapies for CRPC and other agents for treating
skeletal-related events secondary to advanced prostate
cancer or CRPC.
A host of other highly promising agents are under
intense investigation and are poised to improve the
prognosis of patients with advanced disease. The
introduction of new therapeutic options also promises
to create a paradigmshift in the timing of chemotherapy
as well as the combination and sequencing of agents to
extend survival.
Conclusion
Prostate cancer screening remains controversial.
Primary care physicians should discuss the potential
benefits and pitfalls of early diagnosis of prostate
cancer with patients who have at least a 10 year life
expectancy. The choice to pursue prostate cancer
screening must be made after careful consideration of
the implications of a positive diagnosis.
Disclosure
The authors have no potential conflict of interest.
TABLE 2.
Antiandrogen hormonal therapy for prostate cancer
Name (Brand name)
Class
Administration
Notes
Flutamide
Nonsteroidal
250
mg po every 8 hours
Follow LFTs
(
Euflex [Canada],
antiandrogen
w/LHRH analog
Eulexin [US])
Nilutamide
Nonsteroidal
Start at 300 mg po daily x
Follow chest x-ray
(
Anandron [Canada])
antiandrogen
30
days then 150 mg po
Follow LFTs
(
Nilandron [US])
daily w/ LHRH analog or
Baseline PFTs
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)
Depot [Canada only])
300
mg IM weekly or
300
mg IM q2weeks (if orchiectomized)
LFTs = liver function tests
