The lives of rats with an incurable, rapidly progressing form of brain
tumor, similar to glioblastoma in humans, is greatly extended through the
use of two experimental anti-cancer techniques, new research shows.
Rats given the glioblastoma-like tumor cells and left untreated died
from the tumor after an average of 24 days. Rats receiving the experimental
treatments, however, lived up to four times longer-an average of more than
95 days-and a number of rats seem to have been cured.
"We're very excited about this," said Rolf Barth, professor
of pathology with Ohio State University's Comprehensive Cancer Center and
lead author for the study. "We really think that several animals were
cured. These results are exciting because in 26 years of previous work
at this institution, no animals with this tumor were ever cured."
The study was published in a recent issue of Cancer Research.
The Ohio State group combined an experimental technique for disrupting
the blood-brain barrier with an experimental form of radiation therapy
known as boron-neutron capture therapy (BNCT)
For this study, researchers temporarily disrupted the blood-brain barrier
by delivering a highly concentrated mannitol solution to the blood vessels
serving the brain. Blood-brain barrier disruption is being tested in humans
in several clinical trials, including one at Ohio State's Arthur G. James
Cancer Hospital and Research institute, as a way to improve the treatment
of brain cancer.
The experimental radiation treatment, BNCT, uses boron-containing drugs
that localize in tumor cells. The drug is administered and given time to
localize in the tumor and be cleared from the rest of the body.
The tumor is then irradiated with a beam of neutrons. Because alpha
particles travel only about the length of one or two cells, the damage
they do is restricted to nearby cells. BNCT is already being used in Japan
to treat superficial cancers, and a clinical trial of its use in cancer
patients is under way at Brookhaven National Laboratory in New York.
The study tested two boron-containing drugs, sodium borocaptate (BSH)
and boronophenylalanine (BPA). The study sought to determine if blood-brain
barrier disruption would improve the delivery of the drugs to the brain
and thereby improve the effectiveness of BNCT.
The study used six groups of animals, with 8 to 10 animals in each group.
The scientists implanted 1,000 tumor cells into the brain of each of these
"This is a tumor in which 10 tumor cells will invariably kill all
of the animals," said Barth.
Three of the treatment groups were given BSH. In one group, the drug
was given intravenously through a vein in the belly; another group received
the drug intra-arterially through the carotid artery in the neck; the third
group received the drug through the carotid artery, plus blood-brain barrier
disruption. BPA was given in the same three ways to the other three groups
of animals. Two control groups were also used, with 18 animals in each
The tumors in the animals were then irradiated with a neutron beam at
Brookhaven National Laboratory. Of the two drugs, BPA achieved the highest
concentration in tumor cells and produced the most prolonged survival.
Barth, who together with Albert Soloway, professor of pharmacy, co-directs
the BNCT program at the Ohio State's Comprehensive Cancer Center, is working
with Joseph Goodman, associate professor of surgery, and other members
of the research team on a clinical study of the uptake of BSH in patients
with malignant brain tumors. They are also planning a study to determine
if intra-arterial administration of BSH, possibly combined with blood-brain
barrier disruption, can increase boron uptake in brain tumor patients.