Combination Hormone/Vaccine Therapy for Prostate Cancer May Benefit
Patients Whose Disease Returns

BETHESDA, MD -- July 25, 2005 -- A new study finds that a cancer vaccine
combined with hormone-deprivation therapy can help patients with
recurrence of prostate cancer.

The results of this clinical trial, led by scientists at the National
Cancer Institute (NCI), part of the National Institutes of Health,
appear in the August 2005 issue of the Journal of Urology.

This phase 2 trial was designed to treat patients with nonmetastatic
prostate cancer who were experiencing rising levels of prostate-specific
antigen (PSA). Prostate cancer often progresses several years after
treatment with hormone-deprivation therapy.

This is the first study to combine antiandrogen therapy (reducing the
amount of androgens, which are male sex hormones) and a cancer vaccine
for treating prostate cancer, and also the first randomized clinical
trial in this population of prostate cancer patients.

Cancer vaccines are designed either to treat existing cancers or to
prevent the development of cancer. The experimental vaccine used in this
study was designed to strengthen the body's natural defenses against
prostate cancer.

"The question is, what do you do for someone who has already failed
standard therapy with hormones?" said Philip M. Arlen, MD, of NCI's
Laboratory of Tumor Immunology and Biology. "This study was designed to
answer that question and examined a population of patients whose cancers
were resistant to hormone therapy, had no metastatic disease that was
observable by computed tomography (CT or CAT) scan, but had a rising PSA
score, an indicator of recurrence."
NCI scientists randomly assigned 42 prostate cancer patients to receive
either vaccine or second-line antiandrogen treatment, which consisted of
the hormone nilutamide. Nilutamide works by blocking the effects of
excess testosterone, a hormone produced by the body that can promote the
growth of cancer cells.

After the first 6 months of treatment, participants in both arms of the
study -- who had rising PSA levels but no evidence of metastatic disease
-- could choose to receive the other treatment in combination with their
first study treatment.

There were no serious side effects from the vaccine, but some of the
participants receiving nilutamide experienced severe adverse reactions
involving lung toxicities, an uncommon side effect sometimes associated
with the drug.

Median time before the treatment started to fail was 9.9 months for
individuals who received vaccine alone compared to 7.6 months for
patients on nilutamide alone, a difference not considered statistically
significant. However, 12 of the 21 vaccine recipients had nilutamide
added to their treatment regimens after six months. The patients in that
group experienced an additional median time of 13.9 months until
treatment failure, for a total of 25.9 months from the beginning of
their treatments.

The positive effects of combining antiandrogen therapy to vaccine "may
be because the vaccine acts to 'prime' the immune system, and when you
add the hormone treatment, it allowed the vaccine to work even better,"
explained Arlen. "Our study indicates there may well be a synergy
between immunotherapy with vaccines and hormone deprivation."
The rationale for testing a vaccine/hormone therapy combination came
from clinical observations showing that hormone therapy increases the
number of immune cells reaching the prostate gland, thereby allowing
vaccines to work more effectively.

Arlen and his NCI colleagues are planning a follow-up study using the
vaccine and antiandrogen at the same time, instead of sequentially, in
similar patients. They will be testing a more potent, newer prostate
cancer vaccine in the next study. The NCI scientists will also use a
different hormone treatment called flutamide, which has fewer and less
serious side effects than nilutamide.

"Our goal moving forward is to introduce the vaccines into earlier
treatment stages," Arlen said. "We have shown that this therapy is safe
and well-tolerated. Next we want to keep this population of patients
either stable or improving, and also prevent metastatic disease.
Achieving that would be a tremendous benefit in terms of their quality
of life."

REFERENCE:
Arlen PM, Gulley, JL, Todd N, Lieberman R, Steinberg SM, Morin S,
Bastian A, Marte J, Tsang K, Beetham P, Grosenbach DW, Schlom J, Dahut
W. Antiandrogen, vaccine and combination therapy in patients with
nonmetastatic hormone refractory prostate cancer. J Urol, August 2005.

knowledge is power - growing old is mandatory - growing wise is optional    
"Many more men die with prostate cancer than of it. Growing old is
invariably fatal. Prostate cancer is only sometimes so."
http://community.webtv.net/PALMER_ENT/doc