Oct. 21, 2003 STANFORD, Calif. - An old drug may have found a new role treating an incurable form of brain cancer called glioblastoma, according to preliminary research at Stanford University School of Medicine. The drug, called arsenic trioxide, increases the effectiveness of radiation therapy in mice with the disease. The researchers will present their work Oct. 22 at the American Society for Therapeutic Radiology and Oncology.
"Many brain cancers are incurable," said Susan Knox, MD, PhD, associate professor of radiation oncology, who led the study. "The use of arsenic trioxide with radiation may be one way to make the treatment more effective."
Arsenic trioxide has been approved by the U.S. Food and Drug Administration for use in treating a rare form of leukemia. It works in part by releasing damaging molecules called reactive oxygen species, or ROS, that destroy cancer cells. Shoucheng Ning, MD, PhD, a research associate working with Knox, thought the drug would release even higher levels of ROS when coupled with radiation therapy.
The team tested this idea in both the lab dish and in mice. In both cases, exposing glioblastoma cells to radiation within two hours of receiving a dose of arsenic trioxide amplified the effects of radiation treatment on its own.
The mice in this study had tumors formed by injecting human glioblastoma cells under the skin. In these mice, arsenic trioxide alone did not slow the tumor growth, and radiation alone delayed the tumor's growth for only 45 days. The combined treatment eliminated the tumor in four out of five mice and shrunk the tumor by 90 percent in the fifth mouse. The tumors had not begun growing again when the trial ended three months later.
Ning said that the arsenic trioxide dose the mice received is low enough that it would not be toxic in humans. "The concentration we used is already known to be achievable and is well tolerated in humans," he said.
"Based on these results we think the data are compelling enough to move forward with human trials," Knox said. She hopes to start preliminary human trials in conjunction with Iris Gibbs, MD, assistant professor of radiation oncology, by next year. The initial trials will be in recurrent glioblastoma and pediatric brain stem glioma, though Knox hopes to test the therapy in other cancers in the future.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
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