©TheCanadian Journal ofUrology™: International Supplement, April 2014
68
Practical guide to theuseof enzalutamide
> 50%was seen in 8% of patients, with one patient
responding toAAPwhohadnotpreviouslyresponded
to enzalutamide. One patient had a radiographic
response. MedianoverallsurvivalonAAPinthisgroup
following enzalutamide therapy onAFFIRMwas 7.2
months. ToxicityofAAP followingenzalutamidewas
consistentwithpreviousAAP studies.
In a similar report, twenty-seven evaluable men
from four centerswithdiseaseprogression following
enzalutamide on AFFIRM received AAP.
17
In this
groupwhere 60% experienced a 50% decline in PSA
on enzalutamide, only 3%had a> 50%PSAresponse
toAAP. Therewerenoradiographicresponsesand the
medianoverall survivalwas50.2weeks. Toxicitywas
not reported, though no patient discontinued study
drugdue to toxicity.
Conclusion
Enzalutamide is another agent in the expanding
therapeuticfieldformenwithmCRPC. Currentlabeling
supports use following docetaxel, though soon data
shouldbeavailable from thePREVAILstudyregarding
clinicalbenefitandsafety inmenwithmCRPCprior to
docetaxel. The lureof anoral agent likeenzalutamide
for convenience and possible toxicity benefit over
cytotoxic chemotherapy may not reflect actual
outcomes, particularly for those at risk for toxicities
unique to enzalutamide. Findings in the small study
of hormone naïve patients indicate thatmonotherapy
in non-castrate individuals may lead to short term
responsewithout suppressing testosterone levels, but
the long term rates of control, toxicity and survival
will need to be determined. The survival benefit of
enzalutamide formen followingdocetaxel is clear, but
whether this benefit will be potentiated for docetaxel
naïvemenwithmCRPC, and ifenzalutamidewill lead
to response improvement relative to bicalutamide in
docetaxel naïvemen, isyet tobedetermined. Steroids
are required for the safe administrationof abiraterone
acetate, are routinely used with docetaxel, and are
frequentlyused as a comparator in randomized trials
thusbetterunderstanding theeffectsof corticosteroids
in men with mCRPC is warranted. Small series of
patients that have been treated with enzalutamide
on theAFFIRM study and those patients followed in
the compassionate use programs for enzalutamide,
have reported a decrease in the overall response to
subsequent treatment with abiraterone acetate with
prednisone. Thispreliminarydata indicate thatacross
resistancemechanismsdoesexist toenzalutamideand
abiraterone,highlightinganotherareaoffutureresearch
to improve the careofmenwithmCRPC.
Disclosure
Dr. JeanHoffman-Censits has no potential conflict of
interest.
Dr. William Kevin Kelly has no potential conflict of
interest.
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