Possible Treatment for “Chemo Brain”

Reported December 22, 2009

(Ivanhoe Newswire) – Help may be on the way for the legions of cancer survivors who suffer a frustrating decline in cognitive function caused by chemotherapy. It's often referred to as “chemo brain.”

Researchers at the University of Rochester Medical Center (URMC) are working on an insulin-like growth factor, IGF-1, that may be beneficial to those who suffer from chemo brain. “It is not yet clear how our results can be generally applied to humans but we have taken a very significant step toward reproducing a debilitating condition and finding ways to treat it,” principal investigator Robert Gross, M.D., Ph.D., professor of Neurology and of Pharmacology and Physiology at URMC was quoted as saying.

More than 11 million Americans are living today after receiving a cancer diagnosis. Many have endured chemotherapy. Although the side effects during treatment are well known, the lingering neurological effects are more puzzling. Patients often report memory lapses, trouble concentrating, confusion, difficulty multi-tasking and slow thinking for weeks, months, even years after treatment ends.

The URMC team hypothesized that cognitive problems might stem from chemo drugs destroying the ability of brain cells to regenerate in the hippocampus, which is primarily involved in memory formation and mood. They sought a way to find the mechanisms at work and to manage the adverse effects on the brain before, during and after chemotherapy treatment.

Researchers also hypothesized that chemotherapy drugs known to cross the blood-brain barrier would be a bigger threat to brain cells than drugs that do not. They investigated the effects of routinely used doses of cyclophosphamide and fluorouracil, which do cross into the brain, against paclitaxel and doxorubicin, which do not.

All four drugs caused a significant breakdown in brain cell proliferation in the animal model. A statistical analysis of cell regeneration showed a 15.4 percent reduction in new brain cells following fluorouracil, a 30.5 percent reduction following cyclophosphamide, a 22.4 percent reduction following doxorubicin, and a 36 percent reduction following paclitaxel.

Using animal models, researchers administered cyclophosphamide, a mainstay of chemotherapy for breast cancer, because chemo brain is a frequent complaint of people receiving this drug. They then administered IGF-1 prior to and following a conventional cyclophosphamide multiple-dose regimen, and a single, high-dose of cyclophosphamide. The IGF-1 seemed to increase the number of new brain cells in both models, but was more effective in the high-dose model.

“It could be that all of the chemo drugs cross into the brain after all, or that they act via peripheral mechanisms, such as inflammation, that could open up the blood-brain barrier,” said Gross.

“Neurogenesis can also be altered by stress, sleep deprivation and depression, all of which are common among cancer patients,” lead author, Michelle Janelsins, Ph.D., assistant professor of Radiation Oncology at the James P. Wilmot Cancer Center, was quoted as saying. “More thorough studies are needed to understand the interplay of these factors and the long-term effects of chemotherapy on the brain.”

SOURCE: Cancer Investigation, December 17, 2009