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Cancer drugs can cause 'Chemobrain'

MagazineApril 2009 (Vol. 20 Issue 1)Cancer drugs can cause 'Chemobrain'

Most cancer patients notice a loss of mental function, sometimes months after their chemotherapy has ended

Most cancer patients notice a loss of mental function, sometimes months after their chemotherapy has ended. Doctors have belittled their concerns, calling them 'chemobrain' sufferers. Yet, chemobrain is very real for the patients, causing memory loss, confusion, difficulty in concentrating and a general lack of focus.

In fact, it's reckoned that 99 per cent of breast- and ovarian-cancer patients receiving chemo- or radio-therapy will suffer chemobrain, and 61 per cent of these will continue to experience fatigue and memory problems long after the treatment has stopped (ScienceDaily, June 8, 2005).

Researchers at the David Geffen School of Medicine at UCLA were among the first to recognize chemo-brain as a genuine phenomenon that, they believe, can continue for 10 years after stopping treatment.

As lead UCLA researcher Dr Daniel Silverman says: "People with chemo-brain often can't focus, remember things or multitask the way they did before chemotherapy."

In his study, he used a PET (positron emission tomography) scanner to look at the brains of 21 women who had undergone surgery to remove breast tumours five to 10 years earlier, 16 of whom had also received chemotherapy.

The researchers compared the brain scans of these 16 women with those who had surgery only and with 13 healthy controls. The women were asked to perform a series of short-term memory exercises while blood flow to the brain was being monitored. Those who had received chemotherapy had lower metabolic rates in the brain's frontal cortex (ScienceDaily, June 8, 2005).

Since then, others have begun to uncover the mechanism behind chemobrain. Doctors had long held to a firm belief that chemotherapy drugs in cerebral vessels cannot cross into the brain. But new research, led by Mark Noble, professor of genetics, neurobiology and anatomy at the University of Rochester in New York, has revealed that the chemotherapy drugs carmustine, cisplatin and cyto-sine arabinoside are more toxic to brain cells than they are to cancer cells (J Biol, 2006; 5: 22).

Most oncologists dispute these findings, citing studies that have found no cognitive dysfunction even in those receiving high-dose chemo-therapy (Neurology, 2005; 64: 1184-8). Their stand has also been supported by two major studies presented at

the 60th annual meeting of the American Academy of Neurology in Chicago that demonstrated that women given chemotherapy for breast cancer showed no symptoms of chemobrain.

But Noble believes that this is because chemotherapy may have a delayed effect. He has found that the chemotherapy drug 5-fluorouracil (5-FU), for example, causes delayed damage to the myelin sheaths that are essential for normal neuronal functioning (J Biol, 2008; 7: 12).

Christine Meyers, based at the department of neuro-oncology at the M.D. Anderson Cancer Center in Houston, supports Noble's findings, and believes that he has made a major breakthrough in understanding the mechanisms of chemobrain.

"This work is phenomenal because it gives a clear mechanistic basis for chemobrain. A lot of physicians just blew it [chemobrain] off as being impossible because they thought the drugs didn't cross the blood-brain barrier," she says (JAMA, 2008; 299: 2494).

In a mini-review of Noble's work, she states that his findings may help to "guide the development of trans-lational clinical research to protect the nervous system from injury, to better treat injury that has developed as a result of treatment, and to improve the overall quality of life of cancer patients" (J Biol, 2008; 7: 11).

Others are now launching their own research. Bernadine Cimprich, associate professor of nursing at the University of Michigan's School of Nursing, is exploring chemobrain with the aid of functional magnetic reso-nance imaging (fMRI) to see if, after receiving chemotherapy, the brain works differently when presented with problem-solving puzzles.

She is keeping an open mind as to the causes of chemobrain. While it may be a response to drugs, it could also be a reaction to the diagnosis of cancer itself or perhaps a genetic predisposition, as not all cancer patients complain of cognitive effects.

Whatever the cause, the key for Cimprich is that the afflicted women are taken seriously and are helped.

Bryan Hubbard

Reversing chemobrain?

If chemobrain is a reaction to a drug, doctors believe that another drug-Focalin (dexmethylphenidate)-may reverse the worst of the symptoms. This stimulant, usually used to treat attention-deficit/hyperactivity disorder (ADHD), was tested in 154 cancer patients who had been showing the usual symptoms of chemobrain-fatigue and memory loss. Researchers noticed a "significant reduction" in fatigue and an improvement in memory when treated with dosages of 10-50 mg/day (ScienceDaily, June 8, 2005).

Although the research team declared the drug safe, common reactions included insomnia, headache, nervousness, depression, extreme tiredness, confusion and slurred speech-all of which sounds suspiciously like chemobrain.


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