A high-tech device to effectively deliver drugs to tumors in the brain

Brain and other nervous system cancer is the 10th leading cause of death for men and women. Around 18,280 adults died from primary brain and central nervous system tumors in the United States in 2020. Glioblastoma is the most common malignant brain and other CNS tumors and median survival is only 12-15 months.

Why is brain tumor hard to treat? It is due to the blood brain barrier (BBB), a specialized network of blood vessels and cells that shields and protects the central nervous system against circulating toxins or pathogens that could cause brain infections. However, the impenetrability of the BBB also makes it difficult to treat tumors in the brain compared  to those in other organs. Patients with brain tumors have to receive higher doses of chemotherapy to penetrate the BBB and ensure an adequate amount of medication reaches into the brain and kills the tumor cells. The higher dose of chemotherapy will lead to the toxicity to the normal cells, which can result in serious side effects and even death of the patient. To overcome the BBB, scientists have tried to develop many different methods to deliver drugs effectively to the brain so that lower doses of chemotherapy can be used.

Over the last decade, Drs. Bruce and Canoll’s laboratory at the Columbia University Medical Center has been developing a new method to directly administer drugs to the site of the brain tumor, which they call convection enhanced delivery (CED). In CED, a small pump is implanted into the abdomen and connected to a thin catheter under the skin. Wireless technology is used to turn the pump on and off and control the flow rate of medicine that seeps in the tumor tissue.

In a recent study with the CED device, Dr. Bruce used topotecan, a drug that is toxic to glioblastoma cells, to treat five patients who were at least 18 years old with recurrent brain tumors. The patients were infused with topotecan for 48 hours, followed by a 5–7 day washout period before the next infusion, with four total infusions. Patients went about their normal routines at home while treatment continued without any severe side effects. After the fourth infusion, the pump was removed and the tumor was resected. This method is in the early phase of clinical trials (phase 1b) and will be expanded to a larger scale of patients due to test the safety and efficacy of the therapy for recurrent glioblastoma. This novel chemotherapy delivery strategy overcomes the limitation of drug delivery in patients with glioma. The results from this study have recently been published in Lancet Oncology 

There are two limitations in this study. First, there is no comparison group for determination of definitive survival benefit. Second, there is no way to assess the disease progression and treatment response due to effects of local drug infusion and surgical resection. However, in the locally delivered therapy (CED method), the authors used patients as their own control by performing pre-therapy and post-therapy MRIs and PET scans. The CED device effectively gets through the BBB to kill the brain tumor so new classes of drugs and targeted compounds could potentially be used such as high-molecular-weight compounds or viruses.

Reviewed by: Pei-Yin Shih, Maaike Schilperoort

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