©TheCanadian Journal ofUrology™: International Supplement, April 2014
The product should be infused over 60 minutes.
Interruptorslow infusion foracute infusionreactions,
depending on the severity of the reaction. Themost
common adverse reactions are noted in Table 1. In
controlled clinical trials, symptoms of acute infusion
reactions were treated with acetaminophen, IV
histamine (H1 and/or H2 blockers), and low dose
IVmeperidine. Do not resume the infusion if the
sipuleucel-T has been held at room temperature for
greater than3hours. Thepatient shouldbeobserved
for30minutesafter infusion foranyadversereactions.
This entire procedure is repeated for three cycles.
If, for any reason, the patient is unable to receive a
scheduled infusion, the patientwill need toundergo
anadditional leukapheresis if the courseof treatment
is tobe continued. Patients shouldbe advisedof this
possibilityprior to initiating treatment.
Sipuleucel-T treatment followup
Routine mCRPC follow up care is indicated after
sipuleucel-T therapy. Patientsandcliniciansshouldbe
made aware that PSAmaynot beusedas adefinitive
marker for response following immunotherapy. As
notedpreviously, PSAprovides guidance concerning
the men who might be optimum candidates for
immunotherapywithsipuleucel-Tbut isnotareliable
markerof response. There isnoconsensusas towhen
patient should be reimaged, and that the median
time to second treatment on the IMPACT studywas6
monthsdrivenprimarilyby imaging studies.
Immunotherapy generally has the most benefit
with early and lower tumor burden. The dynamics
of immunotherapy are distinct from cytotoxic
chemotherapy whereby the tumor growth rate may
besignificantlyslowed resulting inextendedsurvival
but this can be difficult todetermine in the course of
routine clinical care.
38,39
There is a pressing need to identify predictive
biomarkers in thesettingof immunotherapy. Recently,
Sheikh et al analyzed immunological responses and
overall survival through the assessment of antigen-
specific cellular andhumoral responses ina subset of
men enrolled in the IMPACT study.
40
APCactivation
basedonCD54occurred in thefirstdosewas increased
with the second and third dose preparations; this
increase correlatedwith overall survival. Interferon
gamma (IFN
γ
) enzyme-linked immunosorbent spots
(ELISPOT) alsocorrelatedwithoverall survival. This
preliminary data provides insight onwhich patients
may benefit from improved overall survival through
induction of antigen-specific immune activation and
alsoprovidesdirection for futurebiomarker research.
Conclusions
Improved understanding of the interactions between
the immune systemandprostatecancerhasgenerated
renewed interest in treating prostate cancer with
immunotherapy. While there are several promising
immunotherapeutic agents under study, sipuleucel-T
is clinically available as the first in class antigen-
specific autologous immunotherapy approved for
cancer treatment. Combining sipuleucel-Twithother
agentsandfurtherstudyof theoptimumsequencingof
immunotherapywill continue for thenext fewyears.
41
Understanding the basic principles behind prostate
cancer immunotherapy and the optimum clinical
applicationofsipuleucel-Twillpotentiallybenefitmany
men with minimally symptomatic or asymptomatic
metastatic castration-resistantprostate cancer.
Disclosure
Dr. Leonard G. Gomella serves as a consultant to
Astellas, Bayer,Dendreon and Janssen.
Drs. Gelpi-Hammerschmidt and Kundavram have
nodisclosures.
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