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Doctors See How Cancer Drug Can Damage Kidneys

But the finding shouldn't keep physicians from using Avastin, researchers say

By Ed Edelson
HealthDay Reporter

WEDNESDAY, March 12 (HealthDay News) -- The sometimes controversial cancer drug Avastin can cause kidney damage by doing what it's supposed to -- but in the wrong place, a study shows.

Avastin, whose generic name is bevacizumab, is the first member of a family of drugs designed to attack cancers by cutting off their blood supply. It does this by inhibiting the action of vascular endothelial growth factor (VEGF), a protein that promotes the growth of blood vessels.

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One side effect of Avastin is proteinuria -- excess protein in the urine, an indicator of kidney damage. The new study found that the damage is caused by inhibition of the growth of tiny blood vessels in the kidney, said study leader Dr. Susan E. Quaggin, an associate professor of medicine at the University of Toronto.

The study finding shouldn't stop use of the medication, Quaggin said. "It helps to advise physicians to look out for this complication in treatment and also gives us a better handle on how to use the drug rationally in all cases," she said.

Avastin was first approved by the U.S. Food and Drug Administration for treatment of lung and colon cancer. It became controversial when the FDA approved it for use against advanced breast cancer, despite a 5-4 vote by an advisory committee against that approval. Committee members said the drug's ability to slow tumor progression did not outweigh the damage done by side effects such as blood clots and cardiovascular problems.

Various studies have found proteinuria in anywhere from 21 percent to 64 percent of people given Avastin, the new study noted, but serious damage occurs in only 1 percent to 2 percent of users.

"We don't actually know the true incidence of kidney damage," Quaggin said. "It is true that proteinuria is a very common finding, but it doesn't necessarily mean that a patient shouldn't get this drug. We need more studies to carefully follow the drug and see which patients get proteinuria and how common it is, because currently we don't know."

The new study findings are published in the March 13 issue of the New England Journal of Medicine.

Physicians who use Avastin and any other VEGF inhibitor should be aware of the possibility of side effects elsewhere in the body, said Patricia D'Amore, a senior scientist at the Schepens Eye Institute in Boston, and leader of a study with mice that showed the drug can cause brain damage.

That study showed that Avastin can damage the cell lining that prevents leakage into the brain of fluid from the ventricle, the structure that holds cerebral spinal fluid. That study also showed the kind of blood vessel damage found in the new report, D'Amore said.

"But, in addition, we saw that cells in the ventricle also expressed VEGF and therefore were damaged," she said.

The wider implication of that finding is that VEGF is involved in more than blood vessel growth, D'Amore said. "It has become evident that it has trophic [growth] effects on many nonvascular cells," she said. "This is something that none of us expected to see."

The potential side effects should be taken into account as use widens of Avastin and other VEGF inhibitors now in development, D'Amore said. Some doctors are using the drug against macular degeneration, a condition that causes loss of vision in the elderly.

"In our case, brain pathology, it has been seen in only a few patients treated with Avastin," D'Amore said. "Is it a complication that is going to come up with more chronic use, some kind of maintenance therapy? This is something people need to pay attention to. We have no evidence at all about it, but it is something people should be aware of. All normal tissue is a potential target for Avastin."

More information

To learn more about Avastin, visit the U.S. Food and Drug Administration.

SOURCES: Susan E. Quaggin, M.D., associate professor of medicine, University of Toronto, Ontario, Canada; Patricia D'Amore, Ph.D., senior scientist, Schepens Eye Institute, Boston; March 13, 2008, New England Journal of Medicine

Copyright © 2008 ScoutNews, LLC. All rights reserved.
Last updated 3/12/2008



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Sep 5, 2008
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