Tuesday April 22 2008
5-fluorouracil can be delivered through a drip
“A commonly used chemotherapy drug could be inflicting serious brain damage on cancer patients”, the Daily Mail reported today. It said that research on 5-fluorouracil (5-FU) found that “its damaging effects on the brain can be felt for years after treatment has ended”.
The Daily Telegraph also covered the story and said that the chemotherapy drug is commonly used to treat tumours of the breast, ovary, colon, stomach, skin, pancreas and bladder. The side effects include memory loss, poor concentration and, in extreme cases, seizures, impaired vision and dementia. The Daily Mail says these side effects are known collectively as “chemo brain”, and were often dismissed as fatigue and anxiety caused by cancer.
The newspapers report that this study in mice showed that 5-FU damages the cells that make myelin, the material that insulates the nerve cells and allows them to send signals to each other effectively. This damage was present months after exposure to 5-FU, and the cells were described as being “extensively damaged”.
It’s already known that chemotherapy can be associated with some cognitive side effects in humans, including memory loss and poor concentration. This study specifically investigated what happens at the cellular level when brain cells are exposed to 5-FU in the laboratory or in mice. Its findings suggest that 5-FU’s effects on brain cells could explain some of the cognitive effects of chemotherapy. Further understanding of the potential effects of 5-FU and other chemotherapeutic drugs will help researchers to find ways to potentially minimise and treat these effects.
All medical treatments involve a balance of benefits and harms, and although chemotherapy does have side effects, including the potential for cognitive changes, because of the severity of illness being treated, these risks are probably acceptable to most people.
Where did the story come from?
Dr Ruolan Han and colleagues from the University of Rochester Medical Center and Harvard Medical School carried out the research. The study was funded by the National Institutes of Health, the Susan G. Komen for the Cure foundation, and from the Wilmot Cancer Center. The study was published in the peer-reviewed and open access Journal of Biology.
What kind of scientific study was this?
In this experimental study, the researchers looked at the effects of the chemotherapy drug 5-fluorouracil (5-FU) on rat nervous system cells grown in the laboratory, and on the brains of mice.
The researchers estimated the concentration of 5-FU that would be found in the brain of a person receiving chemotherapy, and exposed different types of brain cells and other cells to this concentration for different lengths of time. The brain cells that were tested included the progenitor cells (immature cells that develop into different types of brain cells, including nerves) and also oligodendrocytes, which are the cells that produce the membrane envelope that insulates the nerve cells and helps them to conduct impulses. They then looked at how many of these cells died when exposed to 5-FU.
Some mice were then given a dose of 5-FU that was estimated to be equivalent to the human treatment dose, and the researchers checked their hearing at up to 56 days after being exposed to 5-FU, as a measure of whether there had been any damage to how the ear sends signal to the brain. They also looked at the mice’s brains using various techniques to see what had happened to the cells.
What were the results of the study?
The researchers found that applying 5-FU to progenitor cells and oligodendrocytes in the laboratory caused a proportion of them to die, even if the cells were not dividing. This proportion grew with increasing concentrations and lengths of exposure. It was found that lower doses could stop cells from dividing.
When the mice were given a dose of 5-FU, it caused some of these types of brain cells to die and stopped some of the cells from dividing. The researchers also showed that there was a delay in the impulses going to the brain from the ears after 5-FU treatment, and this worsened over time. The researchers said this indicated there might be some damage to nerve cell insulation (myelin). When another region of the brain was examined, damage to the nerve cell insulation could be seen as well as a loss of some of the myelin-producing cells (oligodendrocytes). This damage worsened over time. Most of the mice treated with 5-FU did not have damage to the blood vessels or signs of inflammation that would be seen with exposure to radiation.
What interpretations did the researchers draw from these results?
The researchers concluded that this is the first animal model of the delayed damage seen with chemotherapy in humans. They also said that the damage seen with chemotherapy is different to that seen with radiotherapy.
What does the NHS Knowledge Service make of this study?
This study looked at what happens at the level of the cells when the brain is exposed to a chemotherapeutic drug, 5-FU. It should be remembered that there are a wide range of chemotherapy drugs, and it’s not known whether other drugs produce the same effects as those seen with 5-FU.
Although the researchers found differences in how information was relayed between the ears and the brain, this study did not look at the effects on cognition (higher-level mental processes such as thinking, remembering, problem solving). Some other studies have found effects on cognition in other animal models, and in some cases these were only temporary. It will be relevant to humans to investigate, how quickly, if at all, cognitive function recovers, and if there are any factors in humans (such as chemotherapy dose) that determine long-term toxicity.
A judgement of the benefits and harms needs to be made for all medical treatments. Although chemotherapy does have side effects, including the potential for cognitive changes, because of the severity of the illness being treated, these risks are probably acceptable to most people.