©TheCanadian Journal ofUrology™: International Supplement, April 2014
Address correspondence to Dr. Leonard G. Gomella,
Department of Urology, Kimmel Cancer Center, Thomas
Jefferson University, 1025 Walnut Street, Room 1102,
Philadelphia, PA19107USA
Practical guide to immunotherapy
in castration resistant prostate cancer:
theuseof sipuleucel-T immunotherapy
LeonardG.Gomella,MD, FranciscoGelpi-Hammerschmidt,MD,
ChandanKundavram,MD
Department ofUrology, KimmelCancerCenter, Thomas JeffersonUniversity, Philadelphia, Pennsylvania,USA
GOMELLA LG, GELPI-HAMMERSCHMIDT F,
KUNDAVRAMC.Practicalguidetoimmunotherapy
in castration resistant prostate cancer: the use of
sipuleucel-T immunotherapy.
Can J Urol
2014;21
(Suppl 1):48-56.
Introduction:
New treatment options for metastatic
castration resistant prostate cancer (mCRPC) have
become available over the last few years should primary
treatments and androgen deprivation therapies fail.
While historically not considered to be amenable to
immunotherapy, the treatment of advanced prostate
cancer using this approach is an area of intense interest
andnow clinical application.
Materialsandmethods:
Recent literatureoncastration
resistant prostate cancer management with a focus on
immunotherapeuticstrategieswasreviewed. Mechanisms
of action involving the immunologic treatment of cancer
were identified. Agents in clinical trialswithnear term
application in prostate cancerwere also identified.
Results:
Numerous immunotherapeutic agents for
mCRPC are in current clinical trials. The autologous,
active cellular immunotherapy, sipuleucel-T, which
utilizes a patient’s own antigen-presenting cells, is the
only Food and Drug Administration (FDA) approved
agent. Itprovidesa4.1monthsurvivaladvantage. Other
investigationalagents in thisarea includeGVAX, awhole
cell irradiatedvaccine,andavaccinia-PSA-TRICOMpox
virus based approach, all in phase III trials. Immune-
checkpoint inhibitors that enhance T-cell activity and
potentiate antitumor effects are also promising.
Conclusions:
Afirst in classnovel treatmentmodality,
sipuleucel-T, isavailable in theUnitedStates formCRPC.
Other immunotherapies are in development andmay be
available in the near future. Understanding the detailed
patient evaluation, initiation and administration of
sipuleucel-T as described in this paper, will allow this
novel cancer immunotherapy to be better understood
and potentially benefit a larger group of appropriately
selected patients.
Key Words:
castration resistant prostate cancer,
immunotherapy, sipuleucel-T
earlystage localizeddisease. Unfortunately,10%-20%
of prostate cancer patients present with metastatic
disease, andup to one-third of patientswho present
atanearlierstagewillhavediseaserecurrencedespite
surgical or radiotherapeutic treatment.
2
In over 80%
of men with metastatic disease, primary androgen
ablation leads to initial clinical improvement and
reduction of serum PSA levels. However, almost all
advanced metastatic cancers initially treated with
androgenablationwilldevelop intocastrationresistant
prostate cancer (CRPC), themajor causeofmorbidity
andmortalitydeath in thesemen.
A significant number of medications have been
recently approved for the treatment of CRPC.
3
From 2004 until 2010 only docetaxel was approved
for “androgen independent (hormone refractory)
metastatic prostate cancer”, now referred to as
Introduction
Prostate cancer is the most common non-cutaneous
male cancer and comprises approximately 29% of
all newly diagnosed cancer cases inmen. While the
mortality rate has significantly declined since 1994,
arguablydue to the introduction of routine prostate-
specificantigen(PSA)forearlydetectionand improved
therapies of localizeddisease, at least 29480 prostate
cancer related deaths are anticipated in 2014 in the
United States.
1
The greatest opportunity for curing
prostate cancer occurs when a patient presents with
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