New Drug Delivery Method May Help Fight Aggressive Brain Tumor

Children who suffer from a highly aggressive and deadly type of brain tumor may have new hope when it comes to treatment options.

Researchers from Memorial Sloan Kettering Cancer Center (MSK) and Weill Cornell Medicine, both in New York City, tested an approach that appears to be safe and effective at distributing a drug throughout diffuse intrinsic pontine gliomas (DIPG), a tumor that starts in the brain stem, according to study findings published in The Lancet Oncology.

“It has profound meaning from the standpoint of opening up a door of opportunity to achieve very effective chemotherapeutic administration to a very problematic area,” lead study author Mark Souweidane, M.D., a pediatric neurosurgeon at MSK and Weill Cornell, said in an interview with CURE. “It really revolutionizes the way we think about what therapeutic agents we can now use for kids with DIPG.”

The phase 1 clinical trial included 28 children who had received prior radiation therapy to their tumor. They were enrolled from April 2012 to October 2016. Researchers delivered 124I-8H9, an antibody drug that binds to a protein on the surface of brain tumor cells and emits radiation to kill cancerous cells, using convection enhanced delivery (CED).

Traditional chemotherapy, intravenous or oral tablets, affects every blood vessel in the body and only a tiny fraction gets into the brain tissue, explained Souweidane. “The basic foundation of CED is to do away with all of the systemic problems with inefficiency and exposure, and just go directly to the cause and put a tiny hair-like fiber in the tumor itself under a lot of navigational support in the operating room and hook that up to an externalized pump and administered the chemotherapy directly into the tumor,” he said. The process can last up to 12 hours, noted researchers.

The study showed that CED was safe in children with DIPG at seven different dose levels. The researchers also learned that the drug was well distributed through the tumors based on tracking of the radioactive substance through PET and CT scans, as well as MRI.

Grade 3 side effects were seen in two patients. One patient experienced partial weakness on one side of the body and another suffered from a skin infection. No treatment-related grade 4 side effects or deaths occurred.

DIPGs are more common in children between 5 and 10 years old, according to St. Jude Children’s Research Hospital. Since they begin in the brain stem, it can affect critical body functions, such as breathing, heart rate and swallowing. This type of brain tumor is so challenging to treat because it can’t be removed and cancer drugs aren’t getting where they need to go, and worse, research funding is limited, explained Souweidane. “Credibility has been laid to some of the nonprofit organizations and families’ efforts that have started at the ground roots level to change the landscape of this,” he said.

Because of these efforts, he feels a cure is not far out of reach. “This has been the most encouraging thing I have seen in my career with this disease,” said Souweidane. “I have now demonstrated and proven to myself that this can be done in the brain stem safely with a very high rate of efficiency. And now the world is our oyster. Now, how do we optimize it?”