©TheCanadian Journal ofUrology™: International Supplement, April 2014
Acknowledgement
The authors would like to acknowledge Elizabeth Schade
for illustration assistance.
Addresscorrespondence toDr.RobertB.Den,Departmentof
RadiationOncology,Thomas JeffersonUniversityHospital,
111South 11
th
Street, Philadelphia, PA19107-5097USA
Practical guide to theuseof radium223
dichloride
Robert B.Den,MD,
1,2,3
LauraA.Doyle,MS,
2
KarenE. Knudsen,MD
1,2,3,4
1
KimmelCancerCenter, Thomas JeffersonUniversity, Philadelphia, Pennsylvania,USA
2
Department ofRadiationOncology, Thomas JeffersonUniversity, Philadelphia, Pennsylvania,USA
3
Department ofCancerBiology, Thomas JeffersonUniversity, Philadelphia, Pennsylvania,USA
4
Department ofUrology, Thomas JeffersonUniversity, Philadelphia, Pennsylvania,USA
DEN RB, DOYLE LA, KNUDSEN KE. Practical
guide to the use of radium 223 dichloride.
Can JUrol
2014;21(Suppl 1):70-76.
Introduction:
Bone seeking radiopharmaceuticals have
beenused for decades in the palliation of pain from bone
metastasesemerging fromprostatecancer. Recentclinical
evidence has demonstrated an improved survival in
menwithmetastatic castration resistant prostate cancer
(CRPC)with radium 223.
Material andmethods:
A review of the literaturewas
performed to identify the role of radiopharmaceuticals
in the management of prostate cancer. We focused on
prospective trials in order to identify the highest level
of evidence describing this therapy. Further, we focused
on providing a clinical guide for the use of radium 223.
Results:
ThephaseIIIALSYMPCAtrialwhichcompared
radium 223 to placebo inmenwith symptomatic CRPC
demonstrated a statistically significant improvement in
medianoverallsurvivalof3.6monthsandan improvement
in time to first skeletal related event. Therewere higher
rates of myelosuppression and diarrhea with radium
223, however, no clinicallymeaningful differences in the
frequency of grade 3 or 4 adverse events were observed
between the study groups.
Conclusion:
Radium223 is a safe and effective therapy
in men with symptomatic CRPC providing a survival
advantage on par with novel antiandrogens, CYP-17
inhibitors, and chemotherapy. Radium 223 has huge
potential in combination strategies as well as for use
earlier in thenaturalhistoryofmetastaticprostatecancer.
KeyWords:
radium223,castrationresistantprostate
cancer, alphaparticle, radiopharmaceuticals
deprivation therapy through depletion or blockage
of circulating androgens.
3
While initially effective,
mostmendevelop resistance asmanifestedby either
clinical, radiographicormost commonlybiochemical
progression (increase in prostate-specific antigen
despite“castrate” [<50ng/dL] levelsof testosterone).
4
Thedevelopmentofcastrationresistantprostatecancer
(CRPC) signals an inappropriate reactivation of the
androgen receptor (AR) axis resulting in growth and
proliferation.
5
Further, targeting of theARpathway,
through either the disruption of adrenal production
of androgenswithabiraterone acetate,
6,7
or inhibition
of ligand binding using the second generation
antiandrogen enzalutamide,
8
results in increased
survival for this populationofmen. Other Food and
Drug Administration (FDA) approved modalities
which have increased survival for men with CRPC
include chemotherapy
9,10
and immunotherapy.
11
Introduction
Prostate carcinoma is the most common non-
cutaneousmalignancydiagnosed inUSmen and the
second leading cause of cancer related death with
approximately 29480men succumbing to thedisease
in2014.
1
Primary therapy for localizeddiseaseconsists
of either surgical resection or radiation therapy,
2
however, for patients with recurrent or metastatic
prostate cancer, treatment consists of androgen
70
