Canadian Journal of Urology - Volume 23, Supplement 1

© 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.

Recent studies have also suggested a link between

ADT and cognitive impairment,

Alzheimer’s,

and

acute kidney injury.

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).

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.

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.

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