An experimental treatment that combines intense chemotherapy with a radioactive isotope linked to synthesized neurotransmitter is being tested in newly diagnosed cases of high-risk neuroblastoma ? a deadly, hard-to-cure childhood cancer.
The experimental radiopharmaceutical, 131I-MIBG, has already been tested in children with relapsed and resistant neuroblastoma, with encouraging results in reducing tumor size. This has prompted doctors in a new multi-center pilot clinical trial to see if their innovative combination therapy can help improve cure rates for newly diagnosed children and young adults, according to Brian Weiss, MD, trial chair and an oncologist at the Cincinnati Children’s Hospital Medical Center.
In the United Kingdom, fewer than 100 children are diagnosed each year with neuroblastoma, the second most common solid tumour in childhood. In both the United Kindom and the United States, the disease accounts for 7-10% of childhood cancers and accounts for 50% of all malignancies encountered in infants. Most children who get this cancer are diagnosed by 2 years of age.
Tumors originate from neural crest cells or neuroblasts in the sympathetic nervous system. These cells are involved in the development of the nervous system and other tissues. While tumors can appear anywhere in the body, they are most commonly found in the chest and near the adrenal glands, which are located on top of the kidneys. In some children, neuroblastoma occurs in nerve tissue alongside the spinal cord in the neck, chest, abdomen or pelvis.
The cancer is usually first diagnosed by showing up as a lump or mass in the abdomen, or near the spinal cord in the chest or neck. The disease can spread to bone, the liver, lymph nodes and bone marrow. In high-risk neuroblastoma, the tumor has often spread from its primary site and is harder to treat.
Cure rates for neuroblastoma have plateaued at about 40% and new solutions are needed to improve outcomes, said Weiss, a member of the medical center’s Cancer and Blood Diseases Institute.
No detectable biological sign
“Unlike some diseases, there is no single detectable biological sign of neuroblastoma, so it’s hard to catch early,” he explained. “Children with relapsed disease usually don’t survive more than a few years. We want to see if giving this more intensive treatment right after diagnosis will safely decrease the chances of the cancer coming back.”
Experimental trial with 131I-MIBGMIBG stands for Meta-Iodo-Benzyl-Guanidine, a synthesized form of the adrenal gland hormone and neurotransmitter adrenalin. MIBG concentrates selectively in the body’s sympathetic nervous system, which helps control glands and muscles. When attached to the radioactive isotope iodine-131, it’s known as 131I-MIBG. After being injected, 131I-MIBG targets and is taken up by nerve tumors like neuroblastoma. This exposes the cancer cells to very high doses of radiation from the iodine-131, with minimal toxicity to neighboring normal cells.
Standard treatment for neuroblastoma normally includes several rounds of chemotherapy combined with surgery and external radiation. In the current trial, a round of chemotherapy will be replaced by injection of 131I-MIBG combined with the chemotherapy drugs vincristine and irinotecan. The chemotherapy drugs will kill some of the cancer cells and, according to research, may help 131I-MIBG do a better job of eradicating tumor cells, said Weiss.
As part of the treatment, patients receiving treatment were also given a transfusion of previously collected blood stem cells to boost their blood counts after being injected with the radioactive isotope.
The trial is coordinated through and sponsored by the Children’s Oncology Group (COG), an international research consortium of the National Cancer Institute (National Institutes of Health). Thirteen hospitals in the United States and Canada are currently participating in the trial, which is expected to last two years and include up to 44 newly diagnosed patients who have not received previous treatment for their neuroblastoma.
Data from the trial, considered a small pilot study, will be used to help inform larger subsequent clinical trials testing 131I-MIBG-vincristine-irinotecan therapy for neuroblastoma, according to Weiss. The pilot trial’s initial goal is determining the feasibility of newly diagnosed patients traveling from a participating home/regional medical center to participating specialized centers that will administer the 131I-MIBG part of therapy, and then back to their home center for the remainder of treatment.
For more information:
– NCT01175356 – Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin.
– Video interviewwith Brian Weiss, MD
– Comprehensive, Coordinated Care in the Treatment of Neuroblastoma at the Cincinnati Children’s Cancer and Blood Diseases Institute.
Copyright ? 2012 InPress Media Group/Sunvalley Communication. All rights reserved. Republication or redistribution of InPress Media Group/Sunvalley Communication content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group/Sunvalley Communication. InPress Media Group/Sunvalley Communication shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Onco’Zine and Oncozine are registered trademarks and trademarks of Sunvalley Communication around the world.