SAN FRANCISCOIn a phase II trial of the chimeric monoclonal
antibody 131I-chTNT-1/B (Cotara), survival in 22 patients with
recurrent glioblastoma multiforme was significantly increased, compared with
that of historical controls.
Expected progression-free survival in patients with this
disease in first relapse is usually no more than 8 to 12 weeks. Despite
inclusion of heavily pretreated patients with multiple relapses, the Cotara
trial showed a median time to progression of 14 weeks and median survival of 27
weeks in patients with recurrent glioblastoma multiforme.
Sunil J. Patel, MD, associate professor of neurosurgery,
Medical University of South Carolina, Charleston, reported the results at the
37th Annual Meeting of the American Society of Clinical Oncology (ASCO), held
in San Francisco.
"The drug has good binding to the tumor, and it can be
given with minimal toxicity," Dr. Patel said. "We’re seeing very
large distribution of the drug into the tumor, and our preliminary phase II
data indicate that there is some efficacy. We haven’t cured anyone, but we’ve
certainly improved survival."
The agent targets a complex of double-stranded DNA and histones
found in necrotic tissue associated with cancer. Radioactive iodine attached to
the antibody kills the tumor.
"By targeting the radiation to regions of the tumor, we
avoid systemic toxicity," Dr. Patel said, "and also significantly
minimize brain toxicity, which can occur with external beam radiation."
The drug, being developed by Peregrine Pharmaceuticals, Inc. (Tustin,
Calif), which sponsored the study, is delivered directly into the brain via two
catheters placed stereotactically into different parts of the tumor. The drug
is infused over 24 to 48 hours in the hospital.
"Like an IV infusion, the tube stays in the head. Patient
can walk around the hospital with the IV pump; then the catheter is taken out
and they go home," Dr. Patel explained.
Dr. Patel and his colleagues at Temple University, the
University of Utah, Carolina Neurosurgery & Spine, and the Barrow
Neurological Institute are getting ready to launch a phase III trial of Cotara
in brain tumor patients.
"It is certainly a promising drug," he said,
"but we still have to show a large number of patients improving. We still
need to treat a few more patients who have been newly diagnosed with the tumor
who have not had previous therapy. That would be an ideal group of