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Angiostatin With Radiation
Enhances Anti-Cancer Effects
July 20, 1998 Adding low
doses of angiostatin  a naturally produced substance that inhibits the
formation of new blood vessels  to standard radiation therapy dramatically
improves the response to cancer treatment in animal models without increasing
toxicity, say researchers from the University of Chicago Medical Center,
Harvard Medical School, and Northwestern University in the July 16 issue
of Nature.
 "Our
finding suggests that radiation therapy, already a standard of cancer
care, could be dramatically improved by simultaneous administration of
relatively small doses of angiostatin," said Ralph Weichselbaum,
M.D., chairman of radiation oncology at the University of Chicago and
director of the study.
Human angiostatin alone produced only a modest
decrease in tumor growth when given to mice with large tumors. Radiation
therapy alone produced a slightly greater response. The combination of
angiostatin and radiation, however, significantly inhibited growth, demonstrating
a powerful synergistic effect, even in mice with very large tumors.
Enhanced Local Control in Prostate Cancer
"This combination could make radiation much more effective at providing
local control of cancer, a crucial part of treatment for many tumors,
including prostate, brain, head & neck and other cancers. It could
even expand the use of radiation therapy to some forms of metastatic disease
without requiring high doses."
The researchers also studied the combination of
radiation plus mouse angiostatin against human cancers, prostate among
them, that had been transplanted into mice. Once again, the combination
was far more effective than the combined effects of each therapy used
alone. For example, where angiostatin alone reduced the tumor volume 16%,
and radiation alone reduced volume 18%, combined therapy reduced the average
tumor volume 64%.
Two Agents Boost One Another
Surprisingly, tumors treated with the combined therapy had fewer blood
vessels than those treated with angiostatin alone. Radiation kills tumor
cells but was not expected to alter tumor blood-vessel formation.
Angiostatin inhibits the growth of new blood vessels
but has no effect on tumor cells. When the team performed additional studies,
however, looking at the effects on the cells that line arteries and veins,
they found that angiostatin not only killed some of these endothelial
cells, but it also sensitized the surviving cells to radiation. So the
radiation, in combination with angiostatin, boosted the drug's ability
to block the growth of new tumor-supplying blood vessels.
"We were particularly pleased by the manner
in which these two agents team up to shrink tumors," Weichselbaum
said. The researchers say they were excited by the remarkably low doses
of angiostatin required to have an impact, when combined with radiation
 far less than the effective doses of the drug when used alone.
Angiostatin is currently in extremely short supply.
"Clinical trials of low doses used briefly along with radiation to
eliminate tumors," Weichselbaum says, "are perhaps the logical
next step."
July
20, 1998. Page last modified December
26. 1998
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