©TheCanadian Journal ofUrology™: International Supplement, April 2014
Address correspondence toDr. GaneshV. Raj, Department
of Urology, TheUniversity of Texas SouthwesternMedical
Center at Dallas, 5323 HarryHines Boulevard, Dallas, TX
75390-9110USA
Emerging therapies in castration resistant
prostate cancer
GregoryR. Thoreson,MD, BishoyA.Gayed,MD, PaulH. ChungMD,
GaneshV. Raj,MD
Department ofUrology,Universityof Texas SouthwesternMedicalCenter atDallas,Dallas, Texas,USA
THORESONGR,GAYEDBA,CHUNGPH,RAJGV.
Emerging therapies in castration resistant prostate
cancer.
Can JUrol
2014;21(Suppl 1):98-105.
Introduction:
Prostatecancercontinues tobe thesecond
leading cause of cancer relatedmortality inmenwithin
theUnitedStates. Despiteaconsistentdecline inprostate
cancermortalityover thepast twodecades, theprognosis
for men with metastatic prostate cancer remains poor
withno curative therapies. In this article,we review the
recentlyapprovedandemerging therapeutics forpatients
with castrate resistant prostate cancer.
Materials and methods:
An advanced search was
conducted on the clinicaltrials.govdatabase, using search
terms “metastatic prostate cancer”, and limiting results
tophase II-IVclinical trials. Clinically relevant emerging
therapeutics were selected and a Medline search for
supportingdocumentswas performed. An emphasiswas
placedonnewlyapprovedandpromisingnewtherapeutics.
Results:
A total of fourFood andDrugAdministration
approved medications and eight investigational agents
were chosen for review. Thebackgroundand roleof these
therapeutics in the treatmentofprostatecancer treatment
is discussed.
Conclusions:
The past few years have yielded a near
exponential increase in treatments formetastaticprostate
cancer, many of which have a unique mechanism of
action. The estimatedmedian survival for patientswith
metastatic prostate cancer remains dynamic aswe begin
to integrate these therapeutics into clinical practice and
determine the optimal sequence and timingof treatment.
KeyWords:
CRPC, emerging therapies, castration
resistant prostate cancer
overall survival. Themedian survival ofpatientswith
advancedmetastatic prostate cancer, who have failed
androgen deprivation therapy, was typically 16 to 20
months in2009.
2,3
Since2009,workbuildingondecades
ofresearch,dissectingmolecularpathways involved in
prostatecancer,hasresultedinfivenovelFoodandDrug
Administration (FDA) approved therapeutic agents,
each of which has shown an improvement in overall
survival. Although thesurvival improvements in these
recently approvedmedications aremodest, nearly all
of them have a distinctmechanism of action, Table 1.
The potential for combining therapies or optimally
sequencingtherapiesmayofferfurtherimprovementsin
thesurvivalofpatientswithmetastaticprostatecancer.
4
As newer drugs progress through the development
pipeline, Table 2, there is real hope for decreasing the
mortality frommetastaticprostate cancer.
Introduction
In 2014 alone, it is estimated that therewill be 233000
new cases of prostate cancer in the United States.
With an estimated 29480deaths, prostate cancer is the
second-leading cause of cancer-relateddeath inmen.
1
Althoughmanypatients presentwith organ confined
disease, there continues tobe a subset of patients that
progress or present with metastatic prostate cancer.
Until 2009, there were only four drugs approved for
the treatment of castration resistant prostate cancer,
withonlyone,docetaxel, that showed improvement in
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