The challenge: Glioblastoma is an aggressive, fast-growing type of brain tumor. The median survival time after diagnosis is 12 to 18 months, and only 5% of patients live five or more years after diagnosis.
Glioblastoma treatment usually starts with surgery to remove as much of the tumor as possible, followed by chemotherapy or radiation to kill any remaining cancer cells — but this approach is far from ideal.
While radiation therapy destroys cancer cells, it can also damage healthy ones in the area, and because chemotherapy is usually given through pills or intravenously, the drugs have to travel through the body to the brain, causing side effects along the way. of the way.
Once chemotherapy drugs reach their destination, the blood-brain barrier – a natural defense designed to keep microbes in the blood out of the brain – blocks most of them. This prevents chemotherapy from being able to effectively kill cancer cells.
Increasing the dosage to get more drugs into the brain is not an option – the side effects would be too severe for patients to tolerate.
“Tumors inevitably grow back,” said Jeffrey Bruce, co-director of the Brain Tumor Center at Columbia University Irving Medical Center. “And when they do grow back, there’s no proven treatment for them.”
“If you pump the drug very slowly… it penetrates the brain tissue.”
pump: Bruce and his colleagues have developed an implantable chemotherapy pump that delivers drugs directly to the site of a brain tumor. In a small phase 1 trial, it worked as expected, saturating the area around the tumor in five people with recurrent glioblastoma.
“If you pump the drug in very slowly, literally several drops per hour, it penetrates the brain tissue,” says Bruce. “The concentration of the drug that ends up in the brain is 1,000 times greater than anything you would likely get from intravenous or oral administration.”
How it works: For the Columbia study, a chemotherapy pump was implanted in each patient’s abdomen. A thin, flexible catheter was then surgically implanted into the area of the brain where residual cancer cells may be located and connected to the pump under the patient’s skin.
Using a needle, the researchers can fill the chemotherapy pump with whatever drug they want — for this test, they used topotecan, a chemotherapy drug commonly used to treat lung cancer that has shown promise as a glioblastoma treatment in previous research.
Over the course of a month, patients received four topotecan treatments, with the researchers using wireless technology to repeatedly turn the chemotherapy pumps on for two days and then off for five.
“Patients were walking, talking, eating – doing all their normal daily activities,” Bruce said, adding that patients couldn’t tell when the pump was delivering medicine and when it was off.
The results: Remarkably, none of the participants experienced serious neurological complications, while MRI scans revealed that the chemotherapy pump had effectively saturated the area around the cancer with the drug.
Although the study was too small to determine whether the treatment could help patients live longer, biopsies of participants’ brains before and after treatment revealed that it significantly decreased the number of actively dividing tumor cells – without affecting their normal brain cells. .
Looking ahead: For future tests of the chemotherapy pump, the researchers hope to work with people who are experiencing glioblastoma for the first time, rather than experiencing a recurrence.
“A lot has already happened to make the tumor more difficult to treat by the time initial therapies fail, so we believe the pump will work even better with newly diagnosed patients,” Bruce said.
“This approach would give us the ability to change treatment over time and consider using other types of chemotherapy that would not be effective if given systemically but could be much more effective when given directly into the brain,” he continued.
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