City of Hope clinical researchers have demonstrated an efficient method of measuring chemotherapy levels in the brain to help make brain tumor treatments more effective.
Jana Portnow, M.D., assistant professor in the Department of Medical Oncology & Therapeutics Research and assistant director of the Brain Tumor Program, recently published results from her study evaluating intracerebral microdialysis in Clinical Cancer Research.
|Thin catheters may be used to measure drug levels in the brain. (Photo by Alicia Di Rado)|
The blood-brain barrier protects the brain and acts as a sieve to keep large, potentially toxic molecules out of the sensitive tissue. Unfortunately, that barrier also can keep critical drugs such as chemotherapy from reaching tumor cells in the brain.
Researchers and physicians must understand how much of a chemotherapy drug can get through the blood-brain barrier so that they can prescribe the best doses to fight tumors in the brain. Portnow found that intracerebral microdialysis can safely measure these chemotherapy levels.
“The method could also serve as an effective tool to measure whether new drugs in development can reach the brain,” said Portnow, the paper’s lead author.
Through intracerebral microdialysis, physicians implant a very thin catheter in the brain at the same time as they resect a patient’s tumor. The catheter has a semipermeable membrane at its tip, which allows physicians to regularly sample brain fluid after a patient receives a dose of chemotherapy. Physicians test the fluid to identify how much of a chemotherapy drug is circulating in the brain.
“We studied the use of temozolomide, which in addition to being a chemotherapeutic agent, also makes cancer cells more sensitive and vulnerable to radiation therapy,” Portnow said.
Portnow found that temozolimide took longer to build up in the brain than previous laboratory studies suggested.
Current guidelines for chemoradiation treatment of gliomas call for administering temozolomide one hour before radiation treatment, but the study hints that treatment might be more effective if the physicians give the drug even earlier.
“We found that that concentration levels in the brain after one hour were as much as seven times lower compared to two to three hours after administration, when levels seemed to peak,” Portnow said.
Portnow notes that additional studies are needed to evaluate whether a change in dosing time would provide more effective chemoradiation treatment.
The team also included Behnam Badie, M.D., Suzette Blanchard, Ph.D., Michael Chen, M.D., Ph.D., An Liu, Ph.D., and Timothy Synold, Pharm.D. The paper was published in November 2009, and funding from the National Institutes of Health, including General Clinical Research Center and K12 grant support, made the research possible.