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Chemo damages brain, study says

Dec 1, 2006 | Los Angeles Times

Cancer chemotherapy can damage the brain, killing crucial brain cells and causing key parts of the brain to shrink, according to two studies released this week.

The new findings add to a growing body of evidence suggesting that the phenomenon of "chemobrain" the mental fuzziness, memory loss and cognitive impairment often reported by cancer patients but often dismissed by oncologists is a serious problem.

"Those of us on the front lines have known this for a long time, but now we have some neuropathological evidence that what we are seeing involves an anatomic change," said Dr. Stewart Fleishman, director of cancer supportive services at Beth Israel Medical Center and St. Luke's-Roosevelt Hospital Center in New York.

The new studies should help convince physicians who are skeptical about the phenomenon, said Fleishman, who was not involved in the research.

Because chemotherapy is a such a crucial component of cancer treatment and cannot be abandoned, scientists are calling for increased research on shielding the brain from its toxic effects and developing more selective cancer drugs.

Several studies have suggested that from 40 percent to 80 percent of cancer patients receiving chemotherapy suffer from chemobrain. The problem is particularly severe for breast-cancer patients, Fleishman noted, because the treatment induces hormonal changes typical of menopause, and these changes also can produce memory problems.

Dr. Masatoshi Inagaki of the National Cancer Center Hospital in Shikoku, Japan, led a team that used high-resolution magnetic resonance imaging to compare the brains of 51 women who received chemotherapy for breast cancer with those of 54 breast cancer patients who had only surgery.

Inagaki and his colleagues reported Monday in the journal Cancer that, one year after treatment, key areas of the brain involved in cognitive processes — including the prefrontal, parahippocampus and cingulate gyri were significantly smaller in the women who had chemotherapy.

The greater the volume loss in those areas, the team found, the greater the difficulty shown by the women in tests of concentration and memory.

When they studied the same women three years after therapy, however, the volumes were about the same in both groups of women, suggesting that the brain has unsuspected recuperative powers.

In the second study, biomedical geneticist Mark Noble and his colleagues at the University of Rochester Medical Center exposed human brain cells and brain-tumor cells grown in a laboratory dish to three of the most commonly used cancer drugs carmustine, cisplatin and cytarabine.

They reported Thursday in the Journal of Biology that low doses of the drugs caused a 60 percent to 90 percent reduction in the viability of the brain cells but had little effect on the tumor cells. To kill 40 percent to 80 percent of the tumor cells required drug doses that killed 70 percent to 100 percent of the brain cells.

Even though the cancer drugs are targeted at replicating cancer cells, the researchers found that both replicating and nonreplicating brain cells were killed.

The team then gave the drugs to mice and autopsied their brains. They found the drugs killed cells in several regions of the brain and cells continued dying, in some cases, for several weeks after treatment ended.

"This is the first study that puts chemobrain on a sound scientific footing," Noble said.

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