|Combination Hormone/Vaccine Therapy
for Prostate Cancer May Benefit Patients Whose Disease
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 II trial (a trial that usually tests the
effectiveness of a drug) was designed to treat patients
with nonmetastatic prostate cancer who were experiencing
rising levels of prostate-specific antigen (PSA), which
can indicate recurrence of the disease. 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, M.D., 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 six 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
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.”
For more information about cancer, visit the NCI Web
site at http://www.cancer.gov or call NCI's Cancer Information
Service at 1-800-4 CANCER (1-800-422-6237).
The National Institutes of Health (NIH) — The
Nation's Medical Research Agency — is comprised
of 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services.
It is the primary Federal agency for conducting and
supporting basic, clinical, and translational medical
research, and investigates the causes, treatments,
and cures for both common and rare diseases. For more
information about NIH and its programs, visit www.nih.gov.