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Antibody May Improve Survival in Recurrent Glioblastomas

Antibody May Improve Survival in Recurrent Glioblastomas

SAN FRANCISCO—In 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 patients."

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