CHAPEL HILL - Clinical trials are now underway at the University of North Carolina at Chapel Hill on a promising new drug in the fight against malignant and recurrent brain tumors that have so far proved very difficult to treat.
The tumors studied, glioblastoma multiformae (GBM) and anaplastic astrocytoma, originate in the brain. Of roughly 13,000 malignant brain tumors diagnosed in the United States each year, about 60 percent are GBM and about 20 percent are anaplastics, according to Dr. Matthew Ewend, assistant professor of neurosurgery and section chief of neuro-oncology at the UNC-CH School of Medicine.
"Average survival for patients with glioblastoma multiformae is about one year. It's very malignant and tends to come back at the same site," Ewend explains. "Surgery won't cure it, nor will radiation, although both are of benefit. Chemotherapy to date has had limited success."
Ewend, a member of the UNC Lineberger Comprehensive Cancer Center, says one study is a randomized, phase III clinical trial in which patients with GBM will receive either the new drug SU101 or procarbazine, a standard chemotherapy agent. All participants in this trial will be those whose tumors have returned after previous treatment, including surgery, radiation, and perhaps chemotherapy.
SU101, manufactured by Sugen in Redwood City, Calif., is thought to prevent tumor cell growth by blocking specific molecules on the surface of tumor cells. Laboratory research suggests that these "receptor sites," which attract a hormone-like substance called platelet-derived growth factor (PDGF), appear in increased numbers on tumor cells. Initial clinical studies in 80 patients have shown that nearly half have a positive reaction to the drug.
"It's been suggested that the cells over-express the PDGF receptor and they stimulate themselves to grow. It is as if they're pouring gas on their own fire," Ewend says. "By blocking or inhibiting that receptor, we might inhibit the cell's ability to grow."
The drug is administered intravenously. Initially, patients will get a dose every day for four days and then once a week for up to a year. Patients with a good response can continue on the medicine beyond that, as long as they're doing well, Ewend says. Adverse effects from the drug include headache, confusion and sleepiness. Some test subjects have developed gastrointestinal upset, but Ewend notes that most people tolerate SU101 very well.
The second study is a phase II clinical trial, which like the GBM study, also is sponsored by Sugen. This preliminary trial will test the effectiveness of SU101 against anaplastic astrocytoma, a slightly lower grade malignancy than GBM.
"The dose has been established and this is an open trial. All enrolled will get the drug, so we can look for evidence of a positive effect against the tumor," Ewend says.
According to the neurosurgeon, anaplastic astrocytoma is very similar to GBM. "Patients may be eight to 10 years younger with a median survival of a few years rather than one year. But it's a high-grade tumor, and people with anaplastic astrocytoma can develop glioblastoma. So aggressive therapy is still required."
Over 20 centers nationally are involved in the GBM phase III trial and more than 15 are in the anaplastic astrocytoma phase II trial. UNC-CH is the only center in North Carolina involved in these SU101 brain tumor studies.
Persons interested in enrolling in either trial should contact Dr. Ewend at 919-966-1374.
Note to reporters: Dr. Matthew Ewend can be contacted at 919-966-1374; email: ewend@med.unc.edu