Researchers at Columbia University and New York Presbyterian have developed an implantable pump that can continuously deliver chemotherapy drugs directly into the brain to fight hard-to-treat cancer. In a phase 1b trial, patients were able to undergo the therapy while going about their day-to-day activities.
The blood vessels that feed the brain are very selective about what molecules get through. While this blood-brain barrier is important for keeping microbes and foreign material out of the brain, unfortunately most medicines are also kept out. That includes chemotherapy drugs for brain cancer given either orally or intravenously, which only penetrate into the brain in low concentrations.
Bypassing this barrier is a key area of research, with scientists finding promise prying it open temporarily using magnetic nanoparticles or ultrasound pulses, or new drug carriers that can slip past the defenses.
For the new study, the team tested an implantable pump system that can deliver chemotherapy drugs straight into the brain. First a small pump is surgically implanted into the patient’s abdomen, then a thin, flexible catheter is fed under the skin up into the part of the brain where the tumor is located.
The idea is that this pump can continue delivering drugs more or less indefinitely. It can be switched on or off wirelessly, and refilled with a needle as needed. The nature of the treatment also means patients can receive it while going about their day as normal, not even being aware of when the pump was on or off.
“If you pump in the drug very slowly, literally at several drops an hour, it penetrates into the brain tissue,” said Jeffrey Bruce, senior author of the study. “The drug concentration that ends up in the brain is 1,000-fold greater than anything you are likely to get with intravenous or oral delivery. The pump can stay in place for a long period of time, so we can give higher doses of chemotherapy directly to the brain without causing the side effects that we get with oral or intravenous chemotherapy.”
In the trial, five patients with recurrent glioblastoma received the pump implants, which delivered the chemotherapy drug topotecan as well as a tracing agent called gadolinium, so the scientists could measure the concentration and distribution of the drug. Patients were given four weeklong treatments in a row, with the pumps turned on for two days and off for five days.
MRI scans taken in the days following treatment showed that the chemotherapy drug was successfully saturating the tumor and the surrounding area. Post-treatment biopsies revealed that the number of active tumor cells decreased significantly, without affecting healthy brain tissue. And importantly, no patients experienced serious neurological complications.
As promising as this trial has been, the team says that the number of patients tested so far is too small to demonstrate a survival benefit, but future trials will investigate further, including testing on patients at earlier stages of the disease.
The research was published in the journal Lancet Oncology. The team describes the work in the video below.
Source: Columbia University
