Monday, November 3, 1997
Researchers find better way
to treat tumors
DRUG UCLA scientists uncover a new method
to deliver chemotherapy
By Kathryn Combs
Daily Bruin Contributor
Brain cancer affects approximately 100,000 persons in the United
States each year. And science has not yet found a cure.
However, an advance in the war against cancer has recently been
made by UCLA researchers. After three years of research trials,
scientists have found a more effective way to deliver chemotherapy
to cancerous brain tumors.
Chemotherapy is a very common treatment that uses
cancer-fighting drugs to stop the division of cancerous cells, in
turn temporarily halting overall tumor growth in the brain.
Before this discovery, doctors could either administer
cancer-fighting drugs to an afflicted patient intravenously or
through a prescription.
Unfortunately both methods cause side effects to the rest of the
body, especially the immune system, although treatment is actually
aimed at the brain.
So doctors began to look at supplying the drug directly to the
brain through the arteries, in order to limit side-effects felt by
the body.
The new method, uses a micro-catheter, a hollow tube
approximately 1 millimeter across, to deliver the drug directly to
arteries within the brain – directly to the area of the brain where
the tumor resides.
However, previous attempts at using this therapy had negative
results. Doctors found that if they delivered the tube into the
artery in the wrong way, there were severe consequences.
"People tried it before and ran into problems such as blindness,
deafness and focal neurological problems such as stroke and
aneurysms," said Dr. Tim Cloughsey, an assistant professor in the
department of neurology.
"We thought that there were unnecessary limitations placed upon
arterial delivery and with the new technology available we should
be able to improve," he said.
"Our main goal was to try to get the highest amount of
chemotherapy in to the brain in the safest way," Cloughsey said,
"And also to determine a way that we can look at patients in the
future."
Dr. Pierre Gobin, a doctor in the department of radiology,
worked with Cloughsey and performed many of the surgical
procedures.
"This is a common procedure for treating ‘vascular
malformations’ such as aneurysms,"Gobin said.
"First we run a guiding catheter – which is about the diameter
of a ballpoint pen cartridge – from the groin to the neck," Gobin
explained.
"Then we run a microcatheter about the diameter of a toothpick
through the larger tube."
According to Gobin, the catheter is then run to an artery just
above the eye where the drug is delivered directly to the part of
the brain where the tumor resides.
"When the micro-catheter is in place we infuse the drug that Dr.
Cloughsey is giving us," said Gobin, explaining that they used a
drug called carboplatin in their trials.
Carboplatin attaches to the DNA of cancerous cells and inhibits
them from replicating effectively. The growth of the tumor then
stops temporarily.
"(As a result) we found that we had a longer time before the
tumor came back, compared to previous studies that used the same
drug either inter-arterially or intravenously," Cloughsey said.
If doctors are able to deliver large amounts of the drug to the
brain without bodily side effects, logically they can fight the
tumor more effectively.
"One of the problems that was limiting us from giving larger
doses was the toxicity," said Cloughsey.
"You can only give so much chemotherapy into the brain," he
said. "(But) we never reached that maximum because we started
having problems with the rest of the body … such as lowering the
white blood cell count temporarily and lowering the platelet count
temporarily."
Cloughsey says that now, however, these side effects can be
avoided, and a higher concentration of the drug can be delivered to
the tumor.
"If you can have a two-fold increase in the amount of drug, you
might get a four-fold increase in rates of survival and efficacy of
the drug. So it’s important to get a higher dose of the drug,"
Cloughsey said.
According to Cloughsey, the approximate time it takes for a
cancerous brain tumor to grow is between eight and 15 weeks if no
treatment is offered to slow down the growth.
In the past, those treated with Carboplatin took ten to 14
weeks, while those treated with Carboplatin delivered with the
microcatheters took 22 weeks for the tumor to fully develop.
In another difference with traditional chemotherapy, the drug is
injected into the the brain with short pulse-like movements instead
of one long and slow injection.
According to Dr. Gobin, this method is more effective because
the drug diffuses throughout the brain more evenly.
"The way we see to mix the drug immediately with the blood flow
is a very strong injection, a forceful amount. So that when it goes
into the blood flow it will diffuse," Gobin said.
Most are optimistic at the prospects of this new therapy.
"It is very promising,"said Dr. Donald Becker, chief of the
division of Neurosurgery at UCLA.
"It is important to be able to deliver higher levels of
chemotherapy directly to the tumor and not other surrrounding
areas.
"It has great promise for future applications … with better
drugs and improved mechanisms of delivering those drugs."