©TheCanadian Journal ofUrology™: International Supplement, April 2014
26
Utilityof LHRH antagonists for advancedprostate cancer
or in thecaseofclinicT3/T4diseasewhere theclinician
is trying to shrink the gland to facilitate a technically
less-demandingoperative experience. In these cases,
some surgeons use degarelix in the hopes of amore
rapid response.
In the setting of intermittent hormonal therapy
(IHT), it is unclear if degarelix offers any advantage
to the traditional LHRH agonists. There is no level I
evidence tosupportdegarelix in thissetting. However,
some clinicians feel the rapidity of onset may be of
advantage for thefirst (andpossiblysubsequent)“on”
cycles. While there have beenmany nuances to IHT
use,mostof thephase III trialshaveuseda6-9month
initial “on” cycle ofADT therapy. The basis for this
initial durationof therapywas the time toPSAnadir
onADT. For the typical patient withM1 disease, it
will take approximately 7months to reachPSAnadir
and theclinicianswhodesigned the IHT trials felt that
nadirPSAshouldbeachievedbeforestarting the“off”
cycle. It is theoretically possible that themore rapid
testosteroneandPSAdeclinewithdegarelixwouldbe
an advantage tousingdegarelix. Furthermore, some
clinicians feel that returnof testosterone levelsduring
the “off” cycle may be more rapid with degarelix
compared to leuprolideand favor itsuse. Again, there
isno level Ievidence fordegarelixoverLHRHagonists
in IHT and the conceptsdescribed are speculative.
Cost considerations
Inmostclinicalsettings,degarelix iscomparablypriced
to commercially available branded LHRH agonists.
As a result, if a prescribing physician believes there
is a clinical benefit of degarelix over LHRH agonists,
therewould be no or little cost/price disincentive to
use thisagent. Tworecentpharma-economicanalyses
havedemonstratedcosteffectiveness.
12,13
However, the
officeoverheadcosts,personalcosts,patient traveland
lost work costs of patients being seenmonthlymust
alsobeconsidered. Inmypracticesettingofahospital-
based clinic tertiary cancer center, many monthly
patient visits for degarelix are “nurse-only” visits
whichdoesnotgenerally impactphysicianworkflow.
However, in the first fewmonths of administration,
especiallyformenwithmoreadvanceddiseaseand/or
othercomorbidities, thevisits fordegarelixalsoentail
aprovider visitwhichmaybewith aphysicianor an
advancedpracticeprovider.
Conclusions
Degarelix is a second-in-class pureGnRH antagonist
that physiologicallyproduces avery rapid reversible
surge-free testosteroneblockade. Available in theU.S.
sinceDecemberof2008, it isamonthlydepotandrogen
deprivation agent FDA-approved to treat men with
advancedprostatecancer. Thepivotalphase IIIclinical
trialcomparison tomonthly leuprolideacetateshowed
equivalency inmaintaining serum testosterone levels
below50ng/dL(traditional castrate level). However,
degarelixeffectwasmuchmore rapid than leuprolide
withover 95%ofmenachieving castrate testosterone
within72hours andanoverall benefit of testosterone
lowering over the first 28 days of use. Longer term
followup studies of thepivotal trial patients suggest
that degarelixmaybemore effective than leuprolide,
but these data remain controversial. Various clinical
situations were discussedwhere degarelixmight be
consideredoveragonistuse. Themaindisadvantageof
degarelix is thesolemonthlydepotdosing. Clinicians
generally have to discuss efficacy and convenience
issueswith theirpatientswhenmakingadecisionon
androgendeprivation therapy.
Disclosure
Dr. Judd Moul has received honoraria from Bayer,
Janssen,Medivation,Astellas andFerring.
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