The use of a "smart" drug that targets cancer cells in the brain following removal of a tumor may provide treatment that can extend the survival of people with the most common form of primary malignant brain tumor, glioblastoma multiforme (GBM).
A phase III research study being conducted at Rush University Medical Center by neurosurgeon Dr. Richard Byrne involves the use of convection-enhanced delivery, a novel drug delivery approach, to facilitate infusion of the study drug, IL13-PE38QQR, into the brain. IL13-PE38QQR is designed to attach to specific receptors on tumor cells that are not present on normal brain cells.
The problem with current treatments for brain tumors is that while neurosurgeons can remove as much as 95 percent or more of a tumor, some cancer cells will remain undetectable and scattered throughout the brain tissue adjacent to the tumor site. Current methods to kill the remaining cancer cells with radiation or chemotherapy have resulted in a median survival rate after initial diagnosis of about nine to twelve months, and normal brain cells can be injured in the process.
Patients in the study first will undergo neurosurgery to remove as much of the GBM tumor as possible. Within a week, magnetic resonance imaging (MRI) will be used to scan the brain tissue around the cavity where the tumor has been removed to identify suspicious areas where cancer cells may remain.
With the target areas identified, Byrne and his team will then perform a second surgical procedure using an image guidance technique to pass catheters through the skull into the brain to reach two to four areas of tissue suspected of harboring residual, infiltrating tumor cells. Following catheter placement, the drug is continually infused or delivered through the catheters into the brain. A pump is used to slowly push the drug solution through the catheters. This method of treatment is referred to as convection-enhanced delivery, or CED. The patient is able to walk around during this time.
IL13-PE38QQR is a hybrid protein that contains the cytokine IL13, which allows the drug to specifically attach or bind to tumor cells that have the IL13 receptor. "Like a key to a lock," the cytokine binds to the receptor and allows the study drug to enter and potentially kill the tumor cells. Normal brain cells remain unaffected because they do not appear to have the IL13 receptor and therefore the study drug does not bind to them.
The positive-pressure, convection-enhanced delivery method is used to diffuse the drug throughout the targeted brain tissue. Convection enhanced delivery to brain tissue allows the drug to bypass the blood-brain barrier, which protects the brain by preventing "foreign substances" such as drugs in the blood from reaching brain tissue, which can occur when drugs are administered systemically. "There are countless success stories of treating tumors that work in cell lines that fail when we try them in the brain, in part because of the blood brain barrier," said Byrne, who is a member of the Chicago Institute of Neurosurgery and Neuroresearch medical group (CINN). He is the principal investigator for the study at Rush.
"Previous studies with this drug have shown that it was safe and that there were some very dramatic responses in terms of eliminating residual tumor in the brain and prolonging patient life. We believe this drug can positively improve life span for some GBM brain tumor patients by destroying the cancerous cells we cannot remove through neurosurgery," said Byrne.