Physicians initially diagnosed 28-year-old Phil Marfuta with tension headaches, which seemed reasonable him since he is a busy graduate student studying physics at Princeton University. However, as the days went on, his headaches did not subside. When a CT scan and an MRI revealed two tumors, he underwent emergency surgery at HUP.
Marfuta's biopsy revealed that one of his tumors was a grade IV glioblastoma multiforme (GBM), which is the most aggressive form of primary brain tumor. Typically once diagnosed, the median survival time for a patient with a GBM is 12 months.
“That kind of news is the kind you don't want to have to call your family and tell them about,” he said.
As is standard with an initial GBM diagnosis, Marfuta received a course of chemotherapy and radiation following his surgery, but his tumors did not respond to these treatments nor to a clinical trial that added an immune modulator to his therapy.
That's when he learned of Cotara® … and became the first patient in the U.S. to be enrolled in this clinical trial.
Targeting Cancer Cells
HUP is one of four sites participating in the clinical trial of Cotara, a biological “guided missile” for the treatment of GBM, a deadly form of brain cancer that is newly diagnosed in more than 10,000 Americans each year. “Brain tumors are fairly rare, but glioblastomas in adults are the most common among them,” said Neurosurgeon Kevin Judy, MD. “And their recurrence rate is 90 percent.”
Cotara is a monoclonal antibody that targets the DNA of cancer cells and carries a radioactive isotope to them, literally destroying the cancer cells from the inside out. GBMs are complicated to treat because filaments of malignant cells spread out like fingers from the tumor and take root deep in the surrounding tissue, making it difficult to remove them without damaging healthy brain cells. This approach targets the cancer cells, while sparing healthy tissue in the brain.
Another challenge in treating brain tumors is the difficulty of delivering therapeutic agents to the brain through the blood-brain barrier (BBB) — the physical shield that serves to protect the brain and central nervous system from potentially dangerous or infectious agents. Cotara is delivered through a method called convection enhanced delivery (CED), which uses a catheter to bypass the BBB and target the specific tumor site in the brain. This type of delivery has been shown to achieve up to a 10,000-fold greater concentration in local drug exposure than using conventional, intravenous drug administration, while minimizing unwanted exposure to the rest of the body. As a result, it may have fewer serious side effects than some other cancer drugs.
“Based on the scientific rationale for Cotara, coupled with some positive but preliminary indications from previous trials, we believe it is important to study this approach as a new option for this deadly disease,” Judy said. “It's a promising agent.”
Precision Accuracy With 3-D Imaging
Cotara's delivery method begins with an exact catheter placement. To ensure this precision, Marfuta first underwent a stereotactic MRI. “This is a fine cut MRI that has undergone a 3-dimensional reconstruction that is then registered directly on the patient's head,” Judy explained. “In this way, the brain tumor can be accurately localized from outside the skull.”
Using these images, Judy made two burr holes into Marfuta's skull and placed the catheters into position inside of the tumor. He then confirmed their placement with a CAT scan.
“It involved just catheters, so compared to a craniotomy, that sounded quite nice,” Marfuta recalled. “When I came to, I had almost no pain. I was shocked at how easily the surgery went.”
The next morning, Marfuta started receiving an infusion of Cotara through the catheter. “The drug is pumped in very slowly over the course of 25 hours,” Judy said. After the infusion was completed, Judy quickly removed the catheters, at the bedside.
Marfuta has made regular follow up visits with Judy since receiving the drug four months ago. Judy said that a recent MRI showed the tumor getting “diffuse.”
“The drug causes the tumor to 'explode' from the inside,” Judy explained. “The diffusion shows that it's working.”
Marfuta feels very strongly about the importance of participating in clinical trials and has even posted an account of his experience on the Young Adults Surviving Glioblastoma’s Web site www.yasg.com.
“I'm very passionate about science, and I really enjoy finding things out and experimenting,” he said. “By participating in this trial, somehow I feel like I've actually done something tangible to help other people who are basically going through the same thing that I am going through.”
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