May 24, 2005 Attaching a radioactive chemical to a compound that binds to tumor cells, physicians can selectively kill those cells and improve treatment for children with neuroblastoma, a cancer of the peripheral nervous system. Using a compound called MIBG in 167 patients with neuroblastoma, researchers achieved a high number of responses with very few side effects.
John M. Maris, M.D., a pediatric oncologist at The Children's Hospital of Philadelphia, reported on a phase 2 trial of MIBG in a presentation today at the American Society of Clinical Oncology annual meeting in Orlando, Fla. Dr. Maris was the principal investigator of the multicenter study, carried out at Children's Hospital, the University of Michigan, and the University of California, San Francisco.
Neuroblastoma, which accounts for 10 percent of all pediatric cancers, often occurs as a solid tumor in a child's abdomen or chest. The most aggressive forms of the disease often are resistant to conventional treatment with surgery and chemotherapy.
The MIBG treatment makes use of the fact that a compound called meta-iodobenzylguanidine selectively concentrates in neuroblastoma tumor cells. When a radioactive isotope of iodine, iodine-131, is attached to MIBG, the MIBG travels to tumor cells, which are killed by the iodine's radiation. Hospital clinicians deliver MIBG as an intravenous infusion in a special lead-lined hospital room that shields parents and staff members from unnecessary radiation exposure.
In Dr. Maris's study, the patients ranged from four months to 25 years old; all had neuroblastoma that was refractory to first-line treatment, or had relapsed. The overall response rate to MIBG was 35 percent, with a higher response when the cancer was restricted to bone or bone marrow, and when the MIBG dose was higher. The main toxic effect was on blood cells, with 28 percent of the patients requiring infusions of hematopoetic (blood-forming) stem cells to counteract damage to their bone marrow cells. Other toxic effects were rare.
"MIBG is a promising therapy," said Dr. Maris. "It's not a cure, but it brings us a step closer to controlling neuroblastoma as a chronic, nonsymptomatic disease."
Dr. Maris is involved in other studies of MIBG as a member of the New Approaches in Neuroblastoma Therapy program, a consortium of 14 universities and children's hospitals working on novel therapies for high-risk neuroblastoma.
Co-authors of the study Dr. Maris presented at ASCO include Gregory Yanik, M.D., of the University of Michigan; Katherine Matthay, M.D., of the University of California, San Francisco; and Patricia Brophy, CRNP, of The Children's Hospital of Philadelphia.
About the Oncology Program at The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia cares for more children with cancer than any other general pediatric hospital in the United States. Its extensive basic and clinical research programs have been recognized recently by Child Magazine, which ranked Children's Hospital first in the nation in pediatric oncology. In the field of neuroblastoma, Garrett Brodeur, M.D., chief of Oncology, has been a pioneer in developing international standards for risk stratification as a guide to neuroblastoma treatment. John M. Maris, M.D., directs a neuroblastoma research laboratory with seven projects focusing on comprehensive translational research. Stephan Grupp, M.D., Ph.D., has pioneered the use of tandem stem cell transplants for children with high-risk neuroblastoma, and has achieved some of the best results ever published in treating these patients.
The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit www.chop.edu.
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