National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
May 19, 2009 • Volume 6 / Number 10

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Featured Article

An Experimental Treatment Improves Survival for Patients with Neuroblastoma

A microscopic view of a typical neuroblastoma with rosette formation A microscopic view of a typical neuroblastoma with rosette formation

An experimental treatment significantly improved progression-free survival in patients with neuroblastoma at high risk for recurrence, including many young children, researchers from the Children’s Oncology Group (COG) reported last week. Speaking at a press briefing sponsored by the American Society of Clinical Oncology (ASCO), the trial’s lead investigator, Dr. Alice Yu from the University of California, San Diego, said the finding makes the treatment—an antibody-based immunotherapy—“the new standard of care” for patients with high-risk neuroblastoma.

Because of the significant early benefit seen in patients given the experimental treatment, randomization in the NCI-sponsored trial was stopped and the trial was altered so that all enrolled patients can receive the immunotherapy. “We are expending an enormous amount of effort to ensure that this treatment can be available to those children with neuroblastoma for whom the immunotherapy has been shown to be effective,” said Dr. John Maris from the Children’s Hospital of Philadelphia and chair of COG’s Neuroblastoma Committee.

Neuroblastoma is the most common cancer diagnosis in the first year of life. The disease arises in children in the developing cells of the sympathetic nervous system, and it often appears as a tumor in the chest or abdomen. Overall, more than 90 percent of those under 1 year of age survive for 5 years, but rates are much lower for patients who have distant disease.

The trial, which will also be presented in 2 weeks at the ASCO annual meeting in Orlando, involved more than 220 patients with certain clinical and biological factors that put them at high risk for recurrence. The trial’s main objective was to determine the role in the treatment of high-risk neuroblastoma of the ch14.18 monoclonal antibody. The antibody stimulates an immune response to the tumor by binding to a glycolipid (a fat molecule attached to a carbohydrate) known as GD2 that sits on the surface of neuroblastoma cells.

All patients in the trial had responded to standard therapy, which includes intensive chemotherapy, surgery, and a stem cell transplant, followed by radiation therapy. Half were then randomized to receive standard treatment with 13-cis-retinoic acid (RA) alone, while the others received RA plus the experimental treatment, consisting of the ch14.18 monoclonal antibody plus an alternating regimen of two immune-stimulating cytokines, GM-CSF and IL-2.

Progression-free survival at 2 years was 66 percent in the immunotherapy arm and 46 percent in the standard treatment arm, and overall survival at 2 years was 86 percent and 75 percent, respectively. Some significant side effects were associated with the immunotherapy, including pain and an accumulation of fluid in the body caused by vascular leakage, but they were “quite manageable and reversible,” Dr. Yu said.

The trial marks several firsts, Dr. Yu noted, including being the first study to definitively demonstrate that a monoclonal antibody-based immunotherapy with cytokines is an effective cancer treatment. NCI’s Cancer Therapy Evaluation Program (CTEP) is sponsoring clinical trials of the ch14.18 monoclonal antibody, and NCI’s Biopharmaceutical Development Program (BDP) at NCI-Frederick is manufacturing the agent. NCI has on hand a supply of ch14.18 that is being used to treat patients in the trial, said Dr. Stephen Creekmore, chief of NCI’s Biological Resources Branch. BDP is continuing to produce the agent, he added, and more will be available in 2010.

NCI is seeking private-sector collaborators for the continued development of ch14.18 through a Cooperative Research and Development Agreement. Based on the trial results, said Dr. Malcolm Smith, CTEP’s associate branch chief for pediatric oncology, several biotechnology companies have expressed interest in further developing the antibody for commercialization.

The COG study will continue as an “open-label” trial so that children with neuroblastoma can receive the effective immunotherapy. NCI will also sponsor a new ch14.18 clinical trial through COG that will allow collection of additional toxicity and safety data to help support an application to the FDA for marketing approval of ch14.18.

The COG study results, Dr. Smith stressed, “are a critical step in a more than 20-year line of research on antibody-based immunotherapy by NCI and NCI-supported researchers to bring a new life-saving treatment to children with aggressive neuroblastoma.”

—Carmen Phillps