©TheCanadian Journal ofUrology™: International Supplement, April 2014
Address correspondence toDr.RobertDreicer,Department
of Solid Tumor Oncology, Cleveland Clinic, 9500 Euclid
Avenue, R35, Cleveland,OH 44195 USA
How toapproach sequencing therapy
inpatientswithmetastatic castration
resistant prostate cancer
RobertDreicer,MD
Department of SolidTumorOncology, ClevelandClinic, Cleveland,Ohio,USA
DREICERR.Howtoapproachsequencingtherapy in
patientswithmetastaticcastrationresistantprostate
cancer.
Can JUrol
2014;21(Suppl 1):93-97.
Introduction:
Rapidprogresshas recentlybeenmade in
understanding the biology of advanced prostate cancer.
This has translated into the development of a number
of novel agents to treat metastatic castration resistant
prostate cancer (mCRPC).
Materials andmethods:
The relevant literature was
retrieved from a search of MEDLINE with appropriate
keywords.
Results:
Therapeutic approaches to mCRPC include
chemotherapy, hormonal manipulation, immunotherapy
and radioisotope therapy. Docetaxel and cabazitaxel are
cytotoxicagentswhichhavedemonstratedamodest impact
on survival. Hormonal manipulation with abiraterone
and enzalutamide have also been reported to be beneficial
inmCRPC. The radioisotope radium223utilizes anovel
approach in treatingmCRPC andwas recently described
in a positive phase III trial. Finally, sipuleucel-T is an
immunotherapy that has a demonstrated overall survival
benefit inmCRPC.
Conclusions:
A number of phase III trials have been
published that describe agents which are beneficial
in treating mCRPC. Future research will focus on
sequencing these agents in a clinically rational and
economically viablemanner.
KeyWords:
radium 223, docetaxel, enzalutamide,
cabazitaxel, castration resistant prostate cancer,
abiraterone
the management paradigm, provided a therapeutic
option that provided real palliative benefit and a
modest impact on survival.
1
However, after several
decadeswithonlymodest changes in the therapeutic
paradigm, rapidprogress inunderstanding thebiology
ofadvancedprostatecancerwitha focusonandrogen
receptorbiologyhas translatedover the last fewyears
intoaperiodofunprecedenteddevelopmentofnovel
agents thathavemoved through theregulatoryprocess
inwhat is now termedmetastatic castration resistant
prostate cancer (mCRPC).
2-7
Given thehighdegreeofbone tropism inadvanced
prostatecancerrenderingstandardobjectiveresponse
measures problematic, the absence of validated
Introduction
Prior to the availability of docetaxel,management of
men with metastatic prostate cancer was relatively
uncomplicated. Patients received testosterone
suppressive therapyeithersurgicallyormedicallyand
then ultimately progressed to “hormone-refractory”
disease subsequentlymanagedwithpalliative intent
second-linehormonal therapyor cytotoxics anddied
shortly thereafter. The introductionof docetaxel into
93
