©TheCanadian Journal ofUrology™: International Supplement, April 2014
40
Secondaryhormonalmanipulation in castration resistant prostate cancer
radiographicprogression-free survivalwas observed
withabiraterone (16.5versus8.3months;hazardratio:
0.53 [95% confidence interval, 0.45-0.62], p < 0.001),
and this was concordant with improvements in
multipleotherclinicallyrelevantsecondaryendpoints
including median times to opiate use for cancer-
related pain, initiation of cytotoxic chemotherapy,
decline inECOGperformance scoreby≥1point, and
PSAprogression. Therewas a trend to improvement
in overall survival (hazard ratio: 0.75) that was not
statistically proven. The toxicity profile associated
with abiraterone appeared very acceptable, with a
low rate of grade 3 or 4 adverse events and similar
ratesofcardiacdisorders. Mainlygrade1or2adverse
effects due to mineralocorticoid-related toxic effects
were more common in the abiraterone-prednisone
group than in theprednisone-alone group, including
hypertension (22% versus 13%), hypokalemia (17%
versus13%),andfluidretentionoredema (28%versus
24%). Abiraterone has been approved by theUnited
States Food and Drug Aadministration and Health
Canada, foruse inmenwithmetastaticCRPCbeforeor
afterprogressionondocetaxelchemotherapy. Arecent
announcementofresults froma largerandomized trial
indicated thatenzalutamidemayhavesimilarbenefits
toabiraterone in thispopulation,andpresentationand
publicationof thesedata is awaited.
37
Conclusions
SHMs in men with CRPC should consider the
presence or absence of metastases, symptoms, and
visceral disease; as well as patient preferences and
available therapies. Maintenance of a castrate state
is essential, and trials of SHMs may be considered
if clinically reasonable but should not delay use of
palliative chemotherapy if need becomes evident.
For men without metastases, observation or clinical
trial participation shouldbe considered the standard
of care. Formenwithmetastases andminimal or no
symptoms, abiraterone plus prednisone has clearly
established benefit in quality and probably quantity
or life given prior to chemotherapy compared to
prednisonealone. Enzalutamidemayprovidesimilar
benefits in thissetting; highqualitydata ismergingat
the timeof thisreport. Theoptimalchoiceorsequence
of these two drugs is uncertain andwill fuel future
debate. The data supporting the use of other SHMs
is very limited, and basedmore in convention than
data. Taking a view, mindful of toxicity, that there
may be value of these as an addition to a strategy of
observation; serial therapystartingwithaNSAA,with
switch to low dose corticosteroid (with or without
abiraterone acetate in men with metastases) in the
absenceofAAWD response isa reasonableapproach.
For other SHMs the evidence of benefit is sparse and
their use cannot be recommended.
Disclosure
The authorshavenopotential conflict of interest.
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