Tuesday, February 10, 1998
Brain cancer drug sparks search for alternatives
RESEARCH New drug approved for study has fewer harmful side
effects
By Matt Grace
Daily Bruin Contributor
Every time brain cancer patients look in the mirror, they are
reminded of their disease. According to Maryanne Thompson-Beatty,
her husband never forget he had cancer.
Personality changes, grotesque gains in weight, osteoporosis and
incessant bruising were a normal part of his abnormal life,
Thompson-Beatty said.
She tried to alleviate the side-effects by reducing the drug
dosages, but his brain would swell from the lack of steroids and he
would lose the ability to speak.
"Steroids create misery for some people, but that’s the only
thing we have," said Dr. Timothy Cloughesy, director of UCLA’s
Neuro-Oncology Program. Quality of life is always top priority –
but eliminating the side-effects of steroid use has been difficult,
Cloughesy added.
"So while we’re trying to come up with new ways to treat these
tumors," Cloughesy said, "we also have to come up with ways which
will help improve their quality of life."
In a response to the need for an alternative to steroids, an
ongoing study at UCLA’s Jonsson Comprehensive Cancer Center, led by
Cloughesy, has created a new drug study that offers hope for brain
tumor patients.
Brain cancer effects one in every 10 thousand individuals each
year, and only five percent of those diagnosed live for more than
five years.
Until now, steroids provided the only effective means of
reducing the brain swelling associated with the growth of brain
tumors. Without steroid medications, the brain balloons in size and
pushes against the skull, resulting in intracranial pressure which
leaves surrounding tissue dysfunctional.
A new drug called hCRF (human cortisol releasing factor),
recently approved to be studied on a clinical basis, may
significantly reduce the need for steroids.
Like steroids, hCRF reduces brain swelling by maintaining the
integrity of blood vessels in the brain.
As tumors burrow through cortical tissue, they quickly build new
vessels to nourish the need for nutrients and blood, and mesh with
existing tissue, making removal difficult.
However, the tumor-made vessels do not have the same physical
integrity as normal vessels. Healthy vessels constitute a
blood-brain barrier which acts as a gateway regulating the traffic
of proteins in and out of the brain.
Defective vessels built by the tumor are leaky; they create
holes in the molecular wall protecting the brain, and consequently
allow an unchecked influx of proteins, Cloughesy said.
Water follows the proteins across the blood-brain barrier and
the brain begins to swell.
According to Cloughesy, hCRF can be given in amounts larger than
those found naturally in the body.
Normally, hCRF is released in the brain by a small gland – the
hypothalamus – as a precursor for the production of a naturally
occurring steroid, known as cortisol.
Cortisol produces the same effect as synthetic steroids,
presumably without the numerous side-effects.
The catabolic steroids used to reduce swelling in brain cancer
patients break down tissue like muscle, skin, and stomach lining,
unlike anabolic steroids, which build tissue.
Steroids are nonspecific; meaning that when they are introduced
into the bloodstream they affect all parts of the body. They help
maintain the integrity of small vessels in the brain, yet they
destroy tissue elsewhere; resulting in radical redistribution of
fat, thinning of vessels elsewhere in the body, personality changes
and weakening of the vertebrae and muscles.
As a result, patients have had to deal with the negative
side-effects of radiation treatments, complications with the tumor
itself and the problems connected with steroids. This makes the few
remaining months or years of life for cancer patients almost
unbearable, according to Cloughesy.
"If they have a relatively shortened life-span," he said, "we
want to make that as good as quality of life as possible."
The evaluation of hCRF offers hope for brain cancer patients in
the near future.
The side-effects of hCRF are flushing of the face and chest and
minor headaches. Yet, Cloughesy is optimistic.
"Usually it’s well-tolerated," he said, "and we’re also going to
learn more about it."
In the meantime, Cloughesy is reassured by his patients’
participating in the evaluation.
"Patients are so willing to try new drugs that they know will
not benefit them," he concluded, "but will benefit somebody in the
future."