© The Canadian Journal of Urology™; 23(Supplement 1); February 2016
informed when these often older patients are placed
on LHRH therapy. This therapy as previously stated
can cause or aggravate the conditions as defined as
part of the metabolic syndrome. They should also be
reminding and encouraging the patient to be compliant
with their regular ingestion of calcium and vitamin D.
Studies suggest that the LHRH antagonist degarelix
(Firmagon) may offer the advantage over LHRH
agonists such as leuprolide for reducing the risk
of cardiovascular events in men with pre-existing
cardiovascular disease; therefore, patients with pre-
existing cardiovascular conditions requiringADT should
perhaps be preferentially treated with degarelix.
7,8
Recently, Sun et al reported a study that assessed the
adverse effects of ADT for prostate cancer delivered as
gonadotropin-releasing hormone (GnRH) agonists or
bilateral orchiectomy. Patients treated surgically had
a significantly lower risk for any fracture, peripheral
arterial disease, and cardiac complications than those
treatedmedically. Therewas no difference in the rate of
diabetes or cognitive disorders between the two groups
initially, but the risk for diabetes increased in those
taking GnRH agonists for greater than 35 months. The
authors concluded that for patientswith prostate cancer
requiringADT, medical treatment with GnRH agonists
carried higher risks of significant complications than
surgical treatment with bilateral orchiectomy.
9
Recent studies have also suggested a link between
ADT and cognitive impairment,
10
Alzheimer’s,
11
and
acute kidney injury.
12
Castration resistant prostate cancer (CRPC)
The termCRPCemphasizes the resistance of the prostate
cancer to castration levels of testosterone (typically
resulting in a serum testosterone level of less than
50 ng/dL).
13
Recently, there has been significant
advances in the pharmacologic management of CRPC,
Table 1. By definition, CRPC refers to the patient on
hormone therapy to keep the testosterone levels castrate,
who exhibits a rising prostate-specific antigen (PSA)
with or without evidence of progression of disease
as shown by local extension and/or soft tissue or
bony metastases. Presently, there is no recommended
treatment if there is no evidence of spread. These
patients should be monitored frequently, depending
on the PSA doubling time, with repeat bone scans or
CT scans to detect the earliest evidence of progression.
Traditionally, the treatment of metastatic CRPCwas
with the oral agents ketoconazole and/or prednisone.
Previously, if these agents failed, the management
primarily would have been with intravenous taxotere
(docetaxel-chemotherapy). There have been some
innovative approaches to re-attacking the androgen
receptor through new testosterone suppressors. In
the “pre-chemotherapy space”, we now have the
oral agent abiraterone (Zytiga) plus prednisone
(5 mg PO bid or 10 mg PO daily) or enzalutamide
(Xtandi). Benefits from these new hormonal agents
are demonstrated by improvements in quality of life
(reduced pain/fatigue, increased physical/emotional
well-being, and decreased/delayed skeletal related
events), and overall patient survival.
13
Abiraterone acetate (Zytiga)
Abiraterone acetate (1000mgPOdaily) is an irreversible
and specific steroidal inhibitor of CYP17 (P450c17), and
is a novel inhibitor of androgen synthesis uniquely
blocking testosterone production in the testes, adrenal
glands, and intra-tumoral prostatic tissue.
14
This
drug exerts its action high up in the steroidogenesis
pathway by blocking the production of other steroids;
consequently, there is a need for the concomitant use
of oral prednisone 10 mg daily.
TABLE 1.
Recent advances in castration resistant prostate cancer treatment
•
Autologous active cellular immunotherapy
∗
Sipuleucel-T (Brand name: Provenge) [not available in Canada]
•
Semi-synthetic taxane
∗
Cabazitaxel (Brand name: Jevtana)
•
Androgen biosynthesis inhibitor
∗
Abiraterone acetate (Brand name: Zytiga)
•
Androgen receptor inhibitor
∗
Enzalutamide (Band name: Xtandi)
•
Alpha-emitting radiopharmaceutical
∗
Radium 223 dichloride (Brand name: Xofigo)
Mak AND Barkin
32