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Prostate Cancer: More
Accurate Test, Longer Life Treatment Revealed in Two Studies
Feb. 18, 2005 A simple
urine test may improve the diagnosis of prostate cancer and a new
treatment appears to prolong life for those stricken with this disease,
according to two new studies. This is the most common cancer for older
men, and 75 percent of all prostate cancer is found in men over 65.
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Did you know?
A man is 33% more likely to get prostate cancer than a woman is
to get breast cancer. |
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Men middle-aged and
senior citizens routinely get blood tests for prostate-specific antigen, or PSA,
to screen for prostate cancer. However, PSA testing has shortcomings:
many men with elevated PSAs don't have prostate cancer and undergo
unnecessary biopsies, which can cause infertility, incontinence, and
impotence. Other men do have prostate cancer, but have normal PSAs,
allowing the cancer to spread undetected.
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A preliminary study from
Children's Hospital Boston, led by Dr. Bruce Zetter, shows that a simple
urine test may improve upon PSA screening. Results appear in the Jan. 21
online edition of the journal Prostate.
The study on prolonging life
was led by researchers at the University of California at San Francisco
and found that the cancer "vaccine" increased survival, on average, by
4.5 months among men with advanced prostate cancer who no longer
responded to other treatments. The results were made public yesterday at
a prostate cancer symposium in Orlando, Fla. (Click here for more on
this study at bottom of page.)
Zetter, a researcher in
the Vascular Biology Program at Children's, is interested in the role of
cell motility -- cells' ability to move and travel -- in helping cancers
to metastasize. He became especially interested in thymosin ί15, a
protein that stimulates cell migration and promotes metastasis in
prostate cancer. Unlike PSA, it is produced almost exclusively by cancer
cells, and is detectable in urine.
In this study, Zetter
and colleagues compared thymosin ί15 levels in urine samples from 121
men with prostate cancer, 15 men with other genitourinary cancers
(kidney or bladder cancer), 81 men with non-malignant prostate disease
(such as prostatitis), 73 men with other non-malignant urologic diseases
(such as urinary tract infection), and 52 healthy men who served as
controls. Thymosin ί15 levels were elevated in men with aggressive or
untreated prostate cancer, but normal or near-normal in healthy men and
men with other genitourinary diseases. Men with aggressive prostate
cancer were 12 times more likely than the healthy controls to have
elevated thymosin ί15.
Notably, nearly half of
cancer patients whose PSA levels were considered normal tested positive
for thymosin ί15. Conversely, many men with other genitourinary diseases
had elevated PSAs, but normal thymosin ί15 values. When PSA and thymosin
ί15 were combined, the combination detected prostate cancer more often
than PSA testing alone, with far fewer false-positives.
Zetter, who is also
Children's Chief Scientific Officer, is now following the long-term
outcomes of men with prostate cancer to determine thymosin ί15's
usefulness as a prognostic predictor in combination with PSA testing.
The Vascular Biology
Program at Children's is also actively studying urinary markers for
other cancers. In a small pilot study, Dr. Marsha Moses and postdoctoral
fellow Dr. Roopali Roy recently found that a compound called ADAM 12,
when detected in urine, is an early marker of breast cancer. Another
group of markers will soon enter formal clinical trials in adults with
prostate, breast, bladder, lung, and colon cancer.
For more information
about Childrens Hospital Boston visit:
http://www.childrenshospital.org/research/.
Prolonging Life
An innovative treatment for
prostate cancer that uses a person's own immune system has been found
for the first time to prolong the lives of patients with the disease,
the most common form of cancer among men.
Although the benefit of prolonging
live by a few months seems moderate, doctors said it is a significant
improvement for patients with few options and little hope. They also
said it represents an important validation for cancer vaccines, a new
approach that doesn't prevent cancer -- the classic approach of a
vaccine -- but instead rallies the immune system to fight the disease.
Cancer vaccines are emerging as a
promising fourth way to combat cancer that could complement the existing
treatments of chemotherapy, radiation and surgery. Vaccines are
particularly appealing to patients because they don't have the
debilitating side effects associated with chemotherapy and radiation.
"This is really the very first
study that has shown a survival advantage for any (cancer) vaccine,"
said Dr. Eric J. Small, a UCSF oncologist who was the principal
investigator of the study.
"What that does for the field is
very exciting. It tells us that we're on the verge of a new era of
therapeutics that will be targeting the immune system."
Small will present the results of
the Phase III clinical study Saturday at the Multidisciplinary Prostate
Cancer Symposium in Orlando.
Prostate cancer is the most common
type of cancer among men, with an estimated 232,090 cases diagnosed each
year. More than 30,300 men die annually of the disease, making it the
second-leading cause of cancer deaths among men after lung cancer.
The study involved 127 men with
prostate cancer that had spread to their bones and who no longer
responded to hormone therapy, the conventional treatment, but who had
not yet experienced pain from the disease. Patients were given either a
placebo or the vaccine -- three doses over a six-week period -- and were
followed for three years.
Patients who received the vaccine
survived, on average, for 25.9 months, compared with 21.4 months for men
who received a placebo, a nearly 20 percent survival improvement. After
three years, three times as many vaccine patients (34 percent) were
still alive, compared with the placebo group (11 percent).
Side effects from the vaccine --
some fever and shaking -- were relatively minor and disappeared within a
couple of days.
Dr. Nicholas Vogelzang, an
independent oncologist who also heads the Nevada Cancer Institute in Las
Vegas, said that while the size of the trial was relatively modest, the
results were "consistent with what we think would be the effect were the
immune system to attack prostate cancer. It would slow it down. It
wouldn't cure it, but people would live longer."
Small cautioned that the vaccine
may not be for all patients, including those with early-stage prostate
cancer and people with "explosive terminal cancer." But he said it
represents an important new option for men with advanced prostate cancer
that has spread but who have yet to experience pain from the cancer.
"It gives our patients an
additional treatment option," Small said. "It offers them hope that
there's something that can control the disease where there aren't a lot
of other options."
The only other option for such
patients, he noted, is a new chemotherapy drug, taxotere, approved by
the FDA last year, which can prolong survival but has serious side
effects.
The vaccine, which is called
Provenge, is being developed by Dendreon, a Seattle-based biotechnology
company. The latest study is a critical step in winning marketing
approval from the Food and Drug Administration, which has already
granted the vaccine "fast track" status.
More importantly, the UCSF study
represents an important proof of concept for cancer vaccines and using
the immune system to fight cancer. Cancer vaccines are under development
to treat melanoma, lymphoma, leukemia and cancers of the colon, breast,
kidney and pancreas as well as the prostate.
Although the human immune system is
programmed to defend the body against invaders such as a cold virus, its
ability to fight cancer is limited because it doesn't easily recognize
tumor cells as foreign. Moreover, one of the effects of cancer's
malignant growth is to suppress the body's immune system.
Cancer vaccines are designed to rev
up the immune system and teach the body's disease-fighting cells --
antibodies and so-called killer T-cells -- to recognize subtle
differences in the cancerous cells so they can attack the cancerous
cells as "foreign" invaders, while leaving healthy cells alone.
Provenge, the prostate cancer
vaccine, takes advantage of a specialized immune system cell, called a
dendritic cell, that chews up foreign invaders and then "presents"
pieces of the invaders on the cell surface so other immune system cells,
namely killer T-cells, can recognize and destroy the invaders.
Patients' blood is collected and
enriched to increase the population of dendritic cells. These cells are
then cultured with a specific protein common to 95 percent of all
prostate cancer cells.
The dendritic cells digest this
protein. When the dendritic cells are put back into patients, they
signal killer T-cells to destroy any other cells with the telltale
protein.
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