©TheCanadian Journal ofUrology™: International Supplement, April 2014
The sipuleucel-T FDA label states the formal
indication as the “treatment of asymptomatic or
minimally symptomatic metastatic castrate resistant
(hormone refractory) prostate cancer”. These men
have progressed on traditional androgen deprivation
therapy (ADT), suchas orchiectomyor gonadotropin-
releasinghormone (GnRH) therapieswithaconfirmed
serum testosterone of < 50ng/dL. Theprogression is
typicallydefinedasarisingPSAwith the identification
ofneworan increasednumberofmetastasis. Imaging
men with CRPC should be performed periodically
to identify earliest signs if metastasis. The optimum
sequenceof bone scanandbody imaging (CTorMRI)
absentsymptoms,hasnotbeendetermined. NaF
18
PET
scanningtodetectoccultbonemetastases isunderstudy
andpotentiallymayallowevenearlier identificationof
metastaticdisease in thisandother settings.
Once metastatic lesions are noted on imaging,
menwith a castrate level of testosterone and usually
a rising are classified as having mCRPC. Over 30%
of men thought to have non-metastatic CRPCwere
found tohavemetastaseswhen screenedvia imaging
ona recent clinical trial.
36
However, thepatient should
be asymptomatic or minimally symptomatic and
not require narcotic medications for cancer-related
pain. According to the NCCNGuidelines (Prostate
Cancer Version 1.2014, accessed December 16, 2013)
sipuleucel-T is appropriate for patients with ECOG
performancestatus0-1andshouldnotbeusedinpatient
with hepatic metastasis or with a life expectancy of
< 6months. It is also listed as second line therapy for
mCRPC. Therearenoformallynotedcontraindications
for the sipuleucel-T therapyon theFDA label.
A CBC should be obtained 1 month before the
first treatment cycle to ensure adequate hematologic
parameters to undergo leukapheresis. In order to
insure adequate access for leukapheresis, a “venous
assessment” at least 1 week before the first cycle is
required todeterminewhetherplacement of a formal
apheresis catheter is needed. Peripheral IV’s are the
preferredmethod of leukapheresis collection; verify
access inbotharms since leukapheresis is adual-arm
procedure. However, somepatientswith inadequate
peripheral access may require an apheresis catheter.
Twenty three percent of patients in sipuleucel-T
clinical trials required an apheresis catheter.
37
Apheresiscatheters thatprovidecentralvenousaccess
are commonly placed by interventional radiology.
Peripherally inserted central catheter (PICC) linesare
usuallynot considered appropriate.
Patients should be informed about the nature of
the leukapheresisprocedure. It can last3-4hoursand
patient should be well hydrated, avoid caffeinated
beveragesonthedayoftheprocedureandeatacalcium
rich breakfast. Loose fitting clothing is encouraged.
Sideeffectsof the leukapheresisprocedurecan include
perioralanddigital tingling, sensationofchills,nausea
and fainting. Photo ID is essential so that proper
sample identification is insured at all steps in the
treatment cycle. The patient shouldbe accompanied
by an adult as theprocedure can cause some fatigue.
The leukapheresis product is then shipped to the
Dendreonprocessingfacilitywhere it is treatedex-vivo
with a recombinant fusion protein, PA2024 (human
PAP fused GM-CSF). The activated autologous
product, now officially called sipuleucel-T is usually
returned within 48-72 hours to the infusion site. It
contains aminimumof 50millionautologousCD54+
cellsactivatedwithPAPGM-CSF,suspended in250mL
of lactatedringers inasealed,patient-specific infusion
bag. It should be stored refrigerated at 2°C-8°C and
not frozen.
In order to minimize infusion reactions, it is
recommended thatpatientsbepremedicatedwith650
mg of acetaminophen and an antihistamine such as
50mg diphenhydramine 30minutes before. Patient
identity must be verified by photo ID. After fax or
e-mail confirmation from the manufacturer that the
product is“approved for infusion”, (post-manufacture
product quality assurance and expiration date and
time) it is infused throughaperipheral IV (18-20gauge
needlepreferred)orappropriatelypreparedapheresis
catheter (if present). It is critical that no in-line filter
or blood component infusion tubing be used in the
infusion set up. Normal saline is the IV solution of
choice. The product should remain in the insulated
shippingcontainerwiththe lid inplaceuntil thepatient
isready toreceive the infusion. Universalprecautions
should be usedwhen handling sipuleucel-T because
asanautologousproduct, it isnot routinely tested for
transmissible infectious diseases and may carry the
risk of transmitting infectious diseases to health care
professionalshandling theproduct.
Post-manufacture product quality assurance
verifies that theminimum requirements of activated
CD54+ cell are present by measuring the increased
expression of the CD54 (also known as ICAM-1), on
the surface of APCs after culture with the PAPGM-
CSF. Theproduct isalsoapproved for infusionbased
on the microbial and sterility results from several
tests:contaminationbyGramstain,endotoxincontent,
and in-process sterility with a 2-day incubation to
determine absence ofmicrobial growth. Thefinal (7-
day incubation) sterility test results are not available
at the time of infusion and will be reported to the
physicianwith any followup asneeded.
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Practical guide to immunotherapy incastration resistantprostatecancer: theuseof sipuleucel-T immunotherapy
