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Blood pressure drug may help brain tumor patients
Source: (cancerfacts.com)
Friday, February 27, 2009
WINSTON-SALEM, N.C. – Feb. 27, 2009 – A widely used blood pressure medication may be the key to preventing the loss of brain function common after radiation treatment, according to a new study.
Led by Dr. Mike Robbins, a professor in the department of radiation oncology at the Wake Forest University School of Medicine, researchers tested in rats a compound similar to the anti-hypertensive drug losartan (Cozaar®) to see if it might prevent the cognition loss that has been closely-associated with radiation therapy for brain tumors.
The findings, recently published in the International Journal of Radiation Oncology, Biology, Physics, appear to validate the hypothesis, and researchers are optimistic that the same theory could easily be applied in a human clinical trial setting because the drug losartan has long been safely prescribed for patients to treat high blood pressure.
"We need to kill cancer cells but also prevent or reduce treatment-related side effects," said Robbins in a prepared statement. "One very interesting feature of this compound is that it has never shown any pro-tumor effects. If anything, it appears to have anti-tumor properties. We're very close to having a compound that will protect the normal brain from cognitive injury as a result of radiation and, at the same time, we may very well increase the likelihood of curing brain cancer patients of their tumors."
An estimated 170,000 patients undergo radiation therapy annually to treat primary brain cancer or tumors that spread to the brain from other sites. At least 50 percent of adult patients who undergo the treatment and live six months or more afterwards experience some level of cognitive decline. In children, the effect is even greater, Robbins said.
"All (children) will have some form of cognitive impairment if they are long-term survivors and, thankfully, with today's technology, most children will survive long-term," he said.
Researchers have theorized from previous studies that radiation may lead to the overproduction of angiotensin II, a peptide that causes blood vessel constriction, and has been associated with decline of brain function. Losartan and similar drugs, called angiotensin-converting enzyme blockers, or ACE inhibitors block the conversion of angiotensin I into angiotensin II, the active form. By binding the enzyme in patients receiving radiation, researchers hypothesized that the drug could prevent or reduce cognitive decline.
Anti-hypertensive drugs, such as losartan, have been shown effective in preventing or minimizing radiation-induced injury in the lungs and kidneys, Robbins said, so testing them in the brain was an obvious next step.
The study involved three groups of 80 rats. Each group was divided in half to either receive radiation or no treatment. Then, each of those halves was divided into two more groups: one group was given L-158,809, the compound similar to losartan, in the drinking water, and one group was given plain drinking water. The rats that received the drug received it before, during and for different time intervals after-radiation.
In addition, a small group of rats continued to receive the drug for only five weeks after radiation.
Researchers found that administering L-158,809 before, during and for as little as five weeks after radiation either prevents or lessens the severity of radiation-induced cognitive impairment.
"The extent of cognitive impairment experienced by patients who undergo radiation therapy varies in terms of how it is recognized," Robbins said. "Sometimes the patient realizes that their short-term memory is fading or that they've lost the ability to multi-task. Instead of waking up in the morning and having a clear idea of what needs to get done that day, patients finds themselves having to write things down. They just can't keep thoughts in their brain."
Sometimes the loss is only noticed by a friend or partner that, but once it is noticed, it is not going to improve. Cognitive decline resulting from radiation is not stable. It is a chronic, progressive condition."
"This study provides hope that we may be able to take a drug that has been prescribed to millions of individuals with essentially very little morbidity and give it to cancer patients and stop them from experiencing cognitive impairment as a result of brain radiation. These drugs are routinely prescribed for the treatment of hypertension, are well-tolerated and exhibit anti-tumor effects," Robbins said. "They appear to be ideal for future clinical trials because they offer the promise of improving the quality of life for brain tumor patients."
SOURCE: press materials provided by Wake Forest University School of Medicine
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