CHAPEL HILL, NC -- A drug-impregnated wafer that releases chemotherapy directly to tumors that have spread to the brain from other cancers is now undergoing safety tests in patients.
Results of this multi-center phase-I clinical trial may have implications for treatment aimed at prolonging the survival of an estimated 50,000 patients in the U.S. with brain cancer metastases, according to principal investigator Dr. Matthew Ewend, assistant professor of neurosurgery at the University of North Carolina at Chapel Hill School of Medicine.
The Food and Drug Administration has already approved the biodegradable polymer wafer for treatment of recurrent malignant primary brain tumors, those originating within the brain itself. Surgically placed into the brain alongside the malignancy, the dime-sized wafers have been shown to improve survival at six months by more than 50 percent. "Average survival with these brain tumors is less than one year. This treatment helps prolong that," the UNC-CH neurosurgeon says.
Ewend likens the wafer to a bar of soap slowly eroding in the shower. "The drug within the wafer reaches the surface and is released into the brain. But the drug that's inside the 'bar of soap' is protected; the water can't get in and deactivate it."
The polymer package for the chemotherapy wafer was initially developed in the 1980s at M.I.T. by Dr. Robert Longer. Animal and human studies led by Johns Hopkins University neurosurgeon Dr. Henry Brem pioneered the wafer's development and led to its approval by the FDA. The wafer contains the drug 1,3,bis(2-chlorethyl)-1-nitrosourea, or BCNU, the only FDA-approved drug for the treatment of primary brain tumors.
According to Ewend, about 20,000 cases of primary brain tumor occur each year in the U.S. compared to about 50,000 metastatic brain malignancies, of which 90 percent arise from lung, breast, and melanoma skin cancers.
As with primary brain tumors, survival is poor for patients with metastatic brain disease. Studies show survival times measured in months, even for patients who receive aggressive treatment, including surgery, radiation, and systemic chemotherapy. "On average, people with just one brain metastasis survive only about a year," Ewend says. "Many drugs cross the blood into the brain poorly, increasing the likelihood of brain tumor relapse," he explains. "In order to get chemotherapy into the brain, you have to choose drugs that have some ability to cross the blood-brain barrier and then you have to give very high doses, which come with a lot of side effects."
The neurosurgeon also points out that even with advances in treatment such as stereotactic radiosurgery, which focuses a single dose of radiation to the tumor site without having to open the skull, these brain tumors recur in 31 percent to 48 percent of patients.
The UNC-CH researcher is optimistic about the clinical trial, which will involve patients whose brain tumors have arisen from a variety of cancers. Evidence from animal studies suggest that the treatment is safe and effective. The researcher's own experience with a handful of individual cases has been positive. Says Ewend: "It allows for high local doses of chemotherapy with no systemic toxicity."
Candidates for the trial are those in need of surgery for metastatic brain tumors. All will receive radiation along with the new treatment. A total of 25 patients will be studied.
The following are centers involved in the phase-I trial: University of North Carolina, Chapel Hill; Brigham and Women's Hospital, Boston, MA; University of Vermont, Burlington, VT; H. Lee Moffitt Cancer Center, Tampa, FL; Veterans Affairs Medical Center, Seattle, WA; and Emory University Medical Center, Atlanta, GA.