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Common Chemotherapy Drug Linked to Memory Problems
Date:4/21/2008

'Chemo brain' a routine side effect of treatment with drug 5-fluorouracil, study says

MONDAY, April 21 (HealthDay News) -- Treatment with a single, commonly used chemotherapy drug causes memory problems and other cognitive difficulties, a common and unpleasant side effect called "chemo brain," a new study found.

Up to 50 percent of women with breast cancer reported having cognitive problems a year after chemotherapy treatment ended, according to one previous study.

Now, researchers from the University of Rochester Medical Center in New York and Harvard Medical School say they've discovered how the chemotherapy drug 5-fluorouracil -- or 5-FU -- affects the central nervous system even long after treatment ends. The hope is this discovery will lead to ways to decrease or eliminate the damage so cognitive functioning is preserved.

"What we found is the damage done short-term is much less than the damage that occurs long-term," said Mark Noble, senior author of the study published in the April 22 issue of the Journal of Biology. "After the drug is stopped, the cellular damage gets worse."

For years, experts questioned whether chemo brain was a result of chemotherapy or having cancer itself, said Noble, director of the University of Rochester Stem Cell and Regenerative Medicine Institute. "Could they be depressed? Was it really organic damage?" he said, listing some of the suggested possible causes.

"What our studies do is demonstrate [that] it is the chemo," he said. And, the damage can occur with treatment with the single drug, not only the "cocktails" of drugs often used to treat cancer.

In a previous study, Nobel and his colleagues demonstrated that three common chemotherapy drugs were more toxic to healthy brain cells than to the cancer cells they were meant to treat. These studies were among the first to establish a biological basis for chemo brain. But the research didn't explain why the cognitive ill effects persist in some patients.

For the new study, Noble and his colleagues exposed cell lines in a laboratory and in mice to doses of 5-FU, and then evaluated the drug's effects. The drug is used to treat malignancies of the breast, ovaries, stomach, colon and other sites.

The researchers found that 5-FU damaged specific kinds of cells in the central nervous system -- immature cells known as progenitor cells, which later differentiate into specialized cells.

Also damaged were cells called oligodendrocytes, which help produce myelin, the fatty substance that coats nerve cells and facilitates communication between cells.

"The damage at eight weeks was considerably greater than one day after treatment," Noble said. "Damage at six months was even greater than at six weeks."

The finding "means that there is a real physiological basis for the symptoms of 'chemobrain,'" said Dr. Christina A. Meyers, chief of the department of neuro-oncology at M.D. Anderson Cancer Center, in Houston, who wrote an accompanying comment. "Until we know enough to develop targeted treatments for it, there is still lots to do about it [and better to have it than the alternative]." Among the remedies are relaxation training to focus attention, exercise, cognitive rehabilitation and medicine such as anti-inflammatory agents, she said.

Another cancer expert praised the study.

"This is a very good animal model," said Dr. Patricia Ganz, director of cancer prevention and control at the University of California, Los Angeles Jonsson Cancer Center.

But she added a caveat: "This does not mean that everybody receiving this drug will have damage to their brain," she said. And, she added, this is the effect of just one chemotherapy drug, 5-FU. Today, 5FU is "rarely used in breast cancer treatment," she said.

Noble hopes to focus next on why the damage continues. Eventually, his research may lead to a treatment that can be given to decrease or eliminate the harm to healthy cells, he said.

More information

To learn more about chemo brain, visit American Cancer Society.



SOURCES: Mark Noble, Ph.D., director, University of Rochester Stem Cell and Regenerative Medicine Institute, Rochester, N.Y.; Patricia Ganz, M.D., director, cancer prevention and control research, University of California, Los Angeles, Jonsson Cancer Center; Christina A. Meyers, Ph.D., professor and chief, department of neuro-oncology, M.D. Anderson Cancer Center, Houston; April 21, 2008, Journal of Biology


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