©TheCanadian Journal ofUrology™: International Supplement, April 2014
TABLE 1.
Therapeutic agents andmechanismof action
FDAapproved Mechanism
Sponsor
Delivery
Prednisone Approval
agents
of action
supplement
date
Sipuleucel-T
personalized antigen Dendreon
IV
no
4/29/2010
presenting cell-based
immunotherapy
Abiraterone
CYP17 inhibitor
Cougar
oral
yes
4/28/2011
Biotechnology
Enzalutamide
AR antagonist
Medivation
oral
no
8/31/2012
Radium 223
alpha-particle
AlgetaASA IV
no
5/15/2013
(Alpharadin)
emitting
radiopharmaceutical
Investigational
Mechanism
Sponsor
Delivery
Prednisone
agents
of action
supplement
ARN-509
AR antagonist
Aragon
oral
no
Pharmaceuticals
TAK-700
CYP17A1 inhibitor
Millennium oral
yes
Pharmaceuticals
TOK-001
CYP17 inhibitor,
Tokai
oral
no
AR antagonist
Pharmaceuticals
OGX-111
second-generation OncoGenex
IV
yes
ASOwith ahigh
Technologies
affinity forCLURNA
OGX-427
second-generation Hoosier
IV
yes
ASOwith ahigh
Oncology
affinity forHsp27
Group
expression
Prostvac
prostate cancer
Bavarian
SQ
no
vaccine
Nordic
Ipilimumab
monoclonal
Bristol
IV
no
antibodyblocking
Myers
CTLA-4
Squibb
Cabozantinib
tyrosinekinase
Exelixis
oral
no
inhibitor
Androgen axis
In 1941, Huggins and Hodges performed a series
of experiments that showed a relationship between
metastatic prostate cancer growth and testosterone
levels.
5
Since this pioneering study, androgen
deprivation therapy (ADT) has been the cornerstone
ofmetastatic prostate cancer therapy. The emergence
ofgonadrotropinreleasinghormone(GnRH)analogues
hasenabledeffectivechemicalcastrationofpatientswith
metastaticprostatecancer.
6
Inaddition, antiandrogens
suchasbicalutamideofferdirectcompetitiveantagonism
of the androgen receptor.
7
Metastatic prostate cancer
is typically responsive to castration: a vast majority
of patients respond toADTwith declines with their
tumor burden, as evidenced by decreased serum
prostate-specific antigen (PSA) levels.
8
Importantly,
ADT iseffective inrelievingsymptomsfrommetastatic
prostatecancerbutdoesnot improveoverallsurvival.
9-11
Despite an initial response of prostate cancer toADT,
ADT inevitablyfailsanddiseaserecurs. Prostatecancer
refractorytoADT istermedcastrationresistantprostate
cancer (CRPC).
12
In2004,a landmarkstudyestablished
thatCRPC isstilldrivenbytheandrogenreceptor,
13
and
99
ThoresonETAL.
