On
April 29, 2010, the Food and Drug Administration (FDA) approved
a new immunotherapy, sipuleucel-T, for the treatment of
patients with asymptomatic or minimally symptomatic
castration-resistant prostate cancer.
Other immunization strategies are being
tested in patients with prostate cancer. A vaccine called GVAX
that is composed of two allogeneic prostate-cancer cell lines
infected with adenoviruses that allow the cells to secrete
GM-CSF was unsuccessful in phase 3 testing.7
However, another product, called PROSTVAC-VF, composed of two
recombinant vaccinia-based viral vectors containing PSA and
three immune costimulatory molecules, prolonged median survival
by 8.5 months in a randomized phase 2 study.Like sipuleucel-T,
PROSTVAC-VF improved survival without improving progression-free
survival. It is now being tested in phase 3 studies.
Other prospects for vaccine development
include peptide vaccines, DNA-based vaccines, and novel
strategies such as targeting antigens to major
histocompatibility complex class I pathways with chemokine–antigen
chimeric molecules.
Another concern with sipuleucel-T
treatment is the cost. The current cost of care for men with
prostate cancer has been estimated to be about $1,800 per
month.The manufacturer has set the cost of a
1-month course of
sipuleucel-T at $93,000, or $23,000 per month of survival
advantage. The high cost may affect use. It is also uncertain
what role sipuleucel-T will ultimately play in the treatment of
prostate cancer, given the other promising treatments in
development.
Castration-resistant prostate cancer was formerly known as
hormone-refractory prostate cancer. However, even after
tumors progress through combined androgen blockade, they retain
dependence on the androgen receptor. Many novel agents are in
development, some of which have shown dramatic antitumor effects
in the earliest phases of clinical testing.
Abiraterone
blocks the synthesis of androgens; 51% of men who were treated
with 1 g of the drug per day had a reduction in PSA levels of at
least 50%, and 27% of patients had a partial tumor response.
Experimental drug MDV3100 blocks nuclear translocation of the
androgen receptor. In a phase 1 and 2 study, antitumor effects
were noted at every dose of the agent, including a reduction in
PSA levels of at least 50% in 56% of patients, responses in
soft-tissue lesions in 22% and in stabilized bone lesions in
56%, and a reduction in circulating tumor-cell counts in 49%.
The prospects for improved therapy for
prostate cancer have never been so encouraging. The poor
prognosis for men with prostate cancer will probably be
substantially improved by the findings that emerge from ongoing
clinical research.