Delivering Chemo Directly Into Brain Tumors Shows Promise
Using a catheter to deliver chemotherapy drugs directly into a deadly type of brain tumor is showing promise in early clinical trials, researchers report.
Malignant gliomas are difficult to treat using standard chemotherapy and radiation treatments. Only about 3 percent of patients diagnosed with a malignant glioma survive five years or more, according to background information in the study.
With the new method, researchers inserted catheters carrying the chemotherapy drug Topotecan (Hycamtin) directly into the tumors of 16 patients with recurrent malignant gliomas.
The patients who received the Topotecan had a median survival of 59 weeks, although a few patients lived much longer. The median time to tumor progression was 20 weeks, and 77 percent of patients survived for at least six months.
"Those numbers are better than any treatment for recurrent gliomas we have now," said study author Dr. Jeffrey Bruce, co-director of the Brain Tumor Center at Columbia University Medical Center in New York City.
Findings from the Phase 1 trial are slated to be presented Monday at the American Association of Neurological Surgeons annual meeting, in San Diego.
Malignant gliomas are typically resistant to treatment for several reasons, explained Dr. Paul Fisher, an associate professor of neurology and pediatrics at Stanford Medical Center and the Beirne Family Director of Neuro-Oncology.
Chemotherapy is typically given orally or intravenously. In brain tumors, chemotherapy is not very effective, because drugs are not able to penetrate the blood-brain barrier, which prevents most drugs in the bloodstream from entering the brain, the researchers wrote.
Malignant gliomas also send out tentacles, making the tumors very difficult to completely remove surgically. Even when there's no tumor visible, microscopic glioma cells usually remain that eventually regrow, Fisher said.
Sen. Edward Kennedy (D-Mass.) is currently battling a malignant glioma.
Topotecan is sold by GlaxoSmithKline and is typically used in lung cancer patients, Bruce said.
In the lab, the drug had been shown to be effective in killing malignant glioma cells, but delivering enough of it through the bloodstream to attack brain tumors would cause too many toxic side effects.
So for four days, using a procedure called convection-enhanced delivery, Topotecan was pumped into tumors in 16 patients through two catheters. The pumping was done very slowly, at a rate of several drops an hour, Bruce said.
Side effects included upper extremity weakness and left parietal syndrome, neurological issues caused by damage to the brain.
The patients had two types of tumors: 10 had a glioblastoma multiforme (GBM), an invasive and fast-growing tumor, while six had anaplastic glioma.
"Topotecan by convection-enhanced delivery has significant anti-tumor effects at doses that are not harmful to normal brain tissue," Bruce said. "These promising preliminary results indicate that this treatment provides a survival advantage that is favorable compared to other treatments that are often used for recurrent malignant gliomas."
The next step will be multi-center Phase 2 clinical trial, which will begin in the next two to three months, Bruce said.
Fisher said the results were encouraging, but the study was limited in that it involved only a small number of patients and two different types of tumors.
"The technology is to be applauded," Fisher said. "We need to be trying new approaches and trying to do things in a different way. Just giving chemotherapy by an IV or radiation is not going to advance the field."
A second study that will also be presented at the conference also explored an alternative method of delivering chemotherapy drugs to malignant gliomas, this time using nanoparticles.
After injecting cancerous glioma cells into immunocompromised mice, researchers injected the mice with controlled-release nanoparticles that were able to carry the chemotherapy drug fluorouracil (Adrucil) to the tumor site.
The University of Virginia researchers then used high-intensity ultrasound to release the agents in the microvessels feeding the tumor.
The chemotherapy drug killed the glioma cells in the mice, the scientists reported.
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