Drug & Device Development

Radiolabeled tumor necrosis therapy shows strong binding in liver procedures

Last Updated: 2004-02-10 16:24:33 -0400 (Reuters Health)

By William Langbein

NEW YORK (Reuters Health) - Intravenous injections doses of Cotara, a radiolabeled tumor necrosis therapy (TNT) targeting monoclonal antibody, achieved between 12% and 29% concentrations in the liver following radiofrequency ablation (RFA) of tumor nodules in a phase I study of six cancer patients, according to a Mayo Clinic study published in the January issue of Cancer Therapy.

Because the delivery of antibody to diseased sites has been so inadequate in the past, many oncologists have shied away from using radiation doses incapable of eliminating common carcinomas.

The findings of the study, however, led the authors to conclude the TNT antibody construct has "excellent potential to become useful after RFA. Zones of necrosis that facilitate [TNT-1/B] antibody binding were probably created after RFA." Dr. Peter Anderson of the Mayo Clinic was the lead author of the study.

In the study, the six patients with different forms of cancer all had metastatic legions in the liver. Surgeons conducted either precutaneous or intra-operative RFA. After the patients' conditions were stable for two consecutive days, they received either a 0.35 mCi/Kg or 0.71 mCi/Kg dose of Cotara. The total doses in the patients ranged between 22 and 55 mCi; infusions were given over 30 minutes.

The authors said no infusion toxicity was observed. The mean concentration of the injected doses in the liver was 28.1%.

Cotara, in development by Peregrine Pharmaceutical Inc., is marketed as a lung cancer treatment in China. It also has received approval from the U.S. Food and Drug Administration for a registration clinical trial for brain cancer.

The Mayo study in liver cancer will be followed by another at Stanford in colorectal cancer, said Peregrine director of clinical affairs Joe Shan.

The studies aim to demonstrate Cotara can "attack a tumor from the inside out," said Shan. Because Cotara (TNT-1/B) is a murine-human monoclonal antibody that recognizes an epitope concentrated in necrotic tissue, it naturally is attracted to the dead tissue. With more oncologists using RFA to ablate tumors, the RFA procedure is creating more potential binding sites for Cotara. The antibody then potentially can irradiate nearby cancer cells, enhancing the RFA treatment.

The authors said after further studies, it may also be possible to use the immunoconjugate as a direct antibody injection at the end of the RFA procedure into the zone of necrosis using temperature monitoring.

Cancer Therapy 2004;1:297-306.