More than 12,000 U.S. infants and children are diagnosed with some type of pediatric cancer every year.
About 650 new cases of Neuroblastoma, the most common cancer in infancy, are diagnosed every year in the United States. Neuroblastoma is the most common non-brain solid tumor in children responsible for 12% of all cancer deaths in children under 15 years of age. It is a cancer of the peripheral nervous system (outside of the brain and spinal cord). Despite very intensive treatment, nearly 50% of children with neuroblastoma have a high-risk form of the disease with poor long-term survival expectancy.
Currently, standard treatment for neuroblastoma uses high doses of chemotherapy (myeoablatve therapy) to destroy as many cancer cells as possible, however it also destroys a portion of normal blood-forming cells, thereby requiring previously collected blood-forming cells to be ‘given back’ in an attempt to restore immune system function and blood cell formation. The drug Isotretinoin, a derivative of vitamin A is administered to these patients to treat any remaining cancer cells; it has been found to prevent the proliferation of neuroblastoma cells. Prognosis for these patients is bleak, as more than 50% die from the disease.
Attempting to find a more effective approach to treatment for neuroblastoma patients, researchers have administered a new form of immunotherapy which has increased the percentage of those who were alive and free of disease progression after two years. In a randomized phase III clinical trial, coordinated by the Children’s Oncology Group (COG), a national consortium of researchers supported by the National Cancer Institute (NCI), part of the NIH, the percentage of patients living and free of disease progression rose from 46% for children receiving the standard treatment to 66% for children receiving immunotherapy plus standard therapy as reported today in the New England Journal of Medicine.
The particular immunotherapy uses an antibody called ch14.18 targeting a substance on the surface of tumor cells called GD2 which is expressed by neuroblastoma, but also present on some normal nerve cells. Early-phase studies demonstrated the safety and activity of ch14.18 when administered with other drugs which stimulate white blood cell growth and a hormone that increases the nuber and activity of certain types of immune cells, boosting the immune system
In this study, “226 children with high-risk neuroblastoma who had responded to myeloablative therapy were randomly assigned to receive standard therapy (isotretinoin), or isotretinoin, ch14.18, and the immune system boosting drugs. The median time these patients were followed in the study was approximately two years. Although the original plan had been to compare outcomes after three years, the study stopped early because of the strongly positive results, allowing those on standard therapy to switch to ch14.18 immunotherapy if they wished.”
“The phase III trial results establish ch14.18 immunotherapy as a new standard treatment for children with high-risk neuroblastoma,” said Alice Yu, M.D., Ph.D., University of California, San Diego and study chair of the clinical trial.
“Toxicities, including pain, low blood pressure, capillary leak (leakage of blood from capillaries in the circulatory system to the surrounding tissue), and hypersensitivity reactions, were encountered with the immunotherapy treatment at a significantly greater rate than compared to those who just received the standard therapy. However, side effects in the immunotherapy group were temporary and primarily resolved when treatment was stopped,” noted authors.
NCI manufactured the agent, providing it to COG for the clinical trial as there was no pharmaceutical company to make ch14.18 when the phase III trial started. NCI continues to manufacture and make available ch14.18 to children with high-risk neuroblastoma through ongoing COG clinical trials.
“These manufacturing activities illustrate the institute’s commitment to developing new treatments for patients with rare cancers for whom treatments are not likely to be developed by industry,” said James H. Doroshow, M.D., director of NCI’s Division of Cancer Treatment and Diagnosis.
United Therapeutics Corp., Silver Spring, MD will eventually take over responsibility for manufacturing and obtaining US Food and Drug Administration approval of ch14.18 for the treatment of high-risk neuroblastoma. Further development of ch14.18 is being done under a cooperative research and development agreement between NCI and United Therapeutics.
“Despite the remarkable success of the ch14.18 phase III trial, there is still much work that needs to be done. We need to identify more effective and less toxic ways to use ch14.18 as well as to develop novel treatments to help children not cured with currently available therapies,” said Malcolm Smith, M.D., Ph.D., associate branch chief, Pediatrics, Clinical Investigations Branch, NCI.
Early Symptoms of neuroblastoma are often vague making diagnosis difficult. By the time symptoms are apparent, 50-60% of neuroblastomas present with metastases. Symptoms which should be discussed with a health care professional are:
* Lump in the abdomen, neck, or chest.
* Bulging eyes.
* Dark circles around the eyes (“black eyes”).
* Bone pain.
* Swollen stomach and trouble breathing in infants.
* Painless, bluish lumps under the skin in infants.
* Weakness or paralysis (loss of ability to move a body part).
Perhaps one of the most important factors in prognosis and treatment of this terrible cancer is the vast amount of information that is unknown regarding neuroblastoma, one of many pediatric cancers which continue to claim lives of children, which is why the results of this new research is so exciting.
September was Pediatric Cancer Awareness Month, with high hopes of bringing attention to childhood cancer and survivorship issues nationally. Sadly very little was heard about it although groups of parents, grandparents and siblings rallied in effort to shed light on devastating childhood cancers that robbed them of their children.
Words from one Ohio Mom, “I just think these children…my child and his memory deserves more. We should have been seeing the color Gold for pediatric cancer awareness month all month long…instead very few people know about it. So many people are asking what they can still do for our family. My answer would be to help spread awareness. Wear your Sam bracelets, wear your cancer stinks t-shirts, buy gold ribbon decals for the back of your car. Please help get the word out in honor of my precious son who lost his life way to soon….and in honor of all of the wonderful children that we have come to know and love along the way. “
Continued research and treatment discoveries, such as this new immunotherapy treatment to fight neuroblastoma and the belief that it may be effective in the treatment of other cancers like melanoma, a type of skin cancer, helps restore hope for those affected by cancer.
For more information regarding pediatric cancer, and how to become involved, the following two organizations focus exclusively on childhood cancer research: www.stbaldricks.org and www.curesearch.org
