powdered chemical compound emerged from two University of
Maryland School of Medicine laboratories more than 10 years
ago with a name destined for oblivion, but a future that now
looks promising as a treatment for the most challenging cases
of prostate cancer.
VN/124-1 is a drug candidate with a name ó galeterone ó a
pharmaceutical company founded on its potential and a record
of strong preliminary results in clinical trials with human
and Drug Administration has put galeterone on a fast track for
approval to treat prostate cancer, which kills about 30,000
men a year in the United States. Researchers in hospitals and
clinics across the country and in Canada are finishing the
trialís second round and preparing for the third, expected
to begin early next year.
Kevin J. Cullen, director of the University of Marylandís
Marlene and Stewart Greenebaum Cancer Center, acknowledged
that results are preliminary, but he said itís an auspicious
can think of maybe one other drug in the 30 years Iíve been
doing oncology that showed these kind of results," Cullen
said. He called it an "incredibly promising start for
Mario Eisenberger, heading the clinical trial at the Sidney
Kimmel Comprehensive Cancer Center at Johns Hopkins, said the
drug has had impressive results, but "I donít think
anyone can say at this point in time whether galeterone is
going to be better than the other" drugs already used to
treat prostate cancer.
galeterone was a medicine, it was a compound born of a
collaboration that began in 1996 between two University of
Maryland researchers, Angela M. H. Brodie and Vincent C.O.
approach was built on work for which Brodie has won some of
the most prestigious awards in the field ó research not in
prostate but breast cancer. In the last 10 years, she won the
Charles F. Kettering Prize and the Dorothy P. Landon-AACR
Prize for Translational Cancer Research for her work in the
1970s and 1980s helping to develop compounds that block
production of estrogen, the female hormone, that fuels the
growth of most breast cancers.
recently, sheís turned her attention to prostate cancer,
which feeds on the male hormone. She wondered if the approach
that worked with estrogen would work with the androgens, or
hormones, that fuel prostate cancer: testosterone and the more
now, one main treatment for the most challenging prostate
cancers has been shutting down androgen production from the
testicles. The procedure, referred to as castration, is most
commonly done today by medication not surgery. The testicles
produce about 90 percent of the bodyís androgen. Most of the
rest is produced by the adrenal glands, and a small measure
from the prostate tumor itself.
Brodie were looking for a way to fight prostate cancer that
continutes after castration.
approach is one in a succession of hormone-based treatments
that have been used for years, but itís different in
combining several effects at once. This one works in three
ways to interfere with androgenís effect on prostate cells.
medication decreases androgen production and interferes with
the process by which the substance binds to the prostate cell
molecule that responds to the hormone, known as the receptor.
These effects have been produced before, but galeterone is the
only medication that also appears to damage the receptor
triple threat showed impressive results in tests with mice
about 10 years ago. Brodie and Njar and their research team
published results in the Journal of Medicinal Chemistry in
2005, concluding that the compound "is a potent inhibitor
of human prostate tumor growth and is remarkably more
effective than castration."
that publication, Tokai Pharmaceuticals, a company in
Cambridge, Mass., named and licensed the compound as "galeterone."
Clinical trials with human patients started in November 2009.
its anticipated growth, Tokai applied in August to sell $75
million of stock in an initial public offering. While its
stock sale is pending, company officials are not available for
to information posted on Tokaiís website, researchers have
given the drug to 200 patients in the first two trial phases.
49 patients in the first trial, 24 showed 30-percent reduction
in prostate specific antigen, or PSA, and 11 showed a
50-percent cut. Elevated levels of PSA can be, but are not
necessarily, a marker for prostate cancer.
second phase, 51 patients ó both with and without
metastasis, or cancer spread beyond the prostate ó followed
for 12 weeks also showed significant PSA reductions. Of this
group, 82 percent to 85 percent experienced reductions of
about a third, three-quarters saw a reduction by at least
said he was struck by the results even in the first phase,
conducted less for effects on the cancer than to see how well
patients can tolerate the medication at low doses. With such
low doses in the first phase of a clinical trial, results like
that are "almost unprecedented," he said.
third phase of the trial, galeterone will be compared to
existing treatments, Brodie and Njar said, and could take up
to another year.
"fast track" can in some cases cut years off the
time it takes to bring a drug to market, Eisenberger said.
causes none of the adverse effects associated with
chemotherapy, including nausea and hair loss. So far, Brodie
said, the chief side effect could be deficiency of cortisol,
but that has not been a problem so far. The hormone plays a
role in regulating blood sugar, suppressing immune response
and metabolizing fat, protein and carbohydrates.
said the effects can include fatigue and itching, but nothing
requiring cortisol treatment.
and Njar are making no bold pronouncements at this point, just
eagerly awaiting further results.
are cautiously optimistic," Njar said.
a wonderful thing if we can save lives," Brodie said.