Timing of Chemo Could Cut Inflammation

Side effects from chemotherapy are common, but researchers have found that the time of day that chemotherapy drugs to treat breast cancer are given has an effect on the amount of damaging inflammation the treatment produces.

Reducing inflammation is important because it is believed to contribute to many of the neurological side effects of chemotherapy, such as depression, anxiety and short-term memory loss.

“I think we know enough about circadian rhythms in terms of physiology that we can start translating these findings into medical research and practice in humans,” said researcher Randy Nelson, a professor of neuroscience at Ohio State’s Wexner Medical Center.

The research team studied the drugs cyclophosphamide and doxorubicin, a common treatment for breast cancer, in female mice. The mice did not have tumors because the study was designed just to examine the inflammatory response to the drugs.

The mice were injected with the drugs two hours after daylight (which is their inactive period) or two hours after lights were turned off (their active period).

Researchers collected tissue and checked for signs of inflammation in the spleen, an important immune system organ. They also looked at two sites in the brain: the hypothalamus and the hippocampus.

They found that injecting mice with chemotherapy drugs in their inactive phase (daylight) increased the expression of genes that promoted inflammation within the spleen. The researchers found increased production of two toxic drug metabolites, products of the chemo drugs. These metabolites are related to inflammation and one of them, doxorubicinol, causes heart damage in some patients.

The pattern was reversed in the brain, however. Mice injected at night had increases in pro-inflammatory gene expression, but showed less evidence of inflammation when injected during the day.

“The timing of when patients receive drugs has the potential to reduce serious side effects,” said study co-author Courtney DeVries, professor of neuroscience at The Ohio State University’s Wexner Medical Center.

“There may be a sweet spot that maximizes the efficacy of the drugs and minimizes the side effects,” DeVries said. “We don’t know that yet.”

The study was published in the journal Scientific Reports.

Other studies have found promising answers to side effects from chemotherapy. Chemotherapies for early-stage breast cancer such as Herceptin increase the risk of heart failure by fivefold, but heart drugs may be able to help.

Canadian researchers gave women undergoing treatment for breast cancer one of two types of heart drugs — beta blockers and ACE inhibitors. They showed fewer signs of heart damage than a placebo group.

Exercise may also help. Many cancer patients undergoing chemotherapy suffer neuropathy, a side effect that causes pain and numbness in hands and feet, but researchers at the University of Rochester Wilmot Cancer Institute found that it can be eased with exercise.

One group of cancer patients took part in a specialized six-week walking routine combined with gentle, resistance-band training. Their neuropathic symptoms were then compared to those in a second group who didn’t exercise.

Those who exercised reported significantly fewer symptoms of neuropathy. The effects of exercise seemed to be most beneficial for older patients.