One of the main obstacles to treating brain tumors is finding a drug that can actually reach the cancer cells it’s meant to fight. A new clinical trial will help City of Hope researchers measure just how well chemotherapy makes its way into the brain.
The blood-brain barrier acts like a strainer to keep large, potentially toxic molecules out of the brain, explained Jana Portnow, M.D., assistant professor in the Department of Medical Oncology & Therapeutics Research and section chief of medical neuro-oncology.
|Jana Portnow (Photo by Kaminsky Productions)|
Unfortunately, that barrier also can keep critical drugs from reaching tumors.
Now, Portnow is studying a technique called intracerebral microdialysis as a way to measure levels of anticancer drugs in the brain.
With intracerebral microdialysis, physicians implant a very thin catheter in the brain at the same time as they remove a patient’s tumor. The catheter has a semi-permeable membrane, 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.
Portnow recently got regulatory approval to use a new version of the catheter designed to measure levels of even larger molecules.
Her new phase I clinical trial will use the microdialysis technique to measure levels of certain proteins in the brain to see how they change in response to treatment with temsirolimus.
Temsirolimus appears to interfere with tumor cells’ growth and ability to nourish themselves. The Food and Drug Administration approved it in 2007 to treat kidney cancer. Researchers also have studied it as a treatment for brain tumors, but it has demonstrated only a modest effect so far.
|Microdialysis catheters similar to this one will help researchers understand how well chemotherapy crosses the blood-brain barrier. (Photo by Alicia Di Rado)|
The clinical trial will test whether enough temsirolimus actually makes it through the blood-brain barrier to interfere with tumor cell growth.
“We don’t know if it’s just not making it to tumor in the brain in high enough concentrations, or it does make it there and is just not as effective as it is against kidney cancer tumors,” said Portnow.
“As a neuro-oncologist, I think it is important to understand not only whether a chemotherapy agent can cross the blood-brain barrier, but also whether it gets into the brain in sufficient amounts to do what it is supposed to do,” she added.
“With this knowledge we can better select appropriate new agents for testing in brain tumor clinical trials.”