Breakthrough neuroblastoma treatment

By Dr. Ananya Mandal, MDSep 29 2010

According to a new study the addition of an experimental immunotherapy drug to the standard regimen of care extended the lives and decreased the risk of a disease recurrence in children with high-risk neuroblastoma. This tumor most frequently originates in one of the adrenal glands, but can also develop in nerve tissues in the neck, chest, abdomen, or pelvis. It forms 12 percent of cancer-related deaths in children under the age of 15 and half of patients with this type of malignancy have the high-risk form.

For this study, researchers included 226 children, 46 percent of who had the conventional treatment were alive after two years, compared to 66 percent of those who also received the immunotherapy, known as ch14.18. After a while the team found significant benefits with ch14.18 and stopped the trial so that all kids could get the beneficial experimental therapy.

The immunotherapy included monoclonal antibodies which are described as molecular “guided missiles” engineered to kill cancer cells by targeting a substance appearing on those cells.

Dr. Malcolm Smith, co-author of the study and associate branch chief for pediatric oncology at the U.S. National Cancer Institute added, “These are young children who have neuroblastoma who receive very intensive treatment with high dose chemotherapy and, despite that, many are not successfully treated.”

Dr. Smith explained that the immunotherapy “is an antibody-based therapy and the antibody recognizes an antigen that's on the surface of the neuroblastoma cells. It binds to the neuroblastoma cells and then recruits immune cells to the neuroblastoma cells to kill the neuroblastoma cells.” He said that the kids who got this immunotherapy did have more side effects, including pain, than those in the conventional-treatment group.

The Children’s Hospital of Philadelphia director and co-author of the study John Maris said, “We expect these findings will change clinical practice, setting a new gold standard of treatment for this often-deadly disease.”

Dr. Amal Abu-Ghosh, a pediatric hematologist/oncologist at Georgetown University's Lombardi Cancer Center, in Washington, D.C. and an independent observer said, “It's a statistically significant improvement, so the kids who received this treatment were less likely to relapse with neuroblastoma.”

Dr. Abu-Ghosh added that the immune therapy is highly unusual in that the National Cancer Institute, not a pharmaceutical company, manufactured the drug. “Now that the trial is over, we will have to find what other resources are available to get the antibody because it's still not commercially available…It still has to do go through the industry.” Towards this end The National Cancer Institute is in talks with United Therapeutics Corp. to seek U.S. Food and Drug Administration approval and to manufacture and market the drug. All this while, clinical trials network is trying to make the drug available to children who need it.

Although there is this breakthrough kids with the disease still have to go through conventional treatment like high-dose chemotherapy followed by stem cell transplantation to replace blood cells lost during chemotherapy, then the drug isotretinoin to kill off any leftover cancer cells.

There was another study in the same issue of the journal that found that children with intermediate-risk neuroblastoma who took a reduced regimen of chemotherapy plus a biologically based treatment were able to live just as long as those receiving conventional duration-and-dose chemotherapy. The dose of chemotherapy used was almost half in the 479 children. At three years, 96 percent of children with this tumor were still alive with the biologic agent and less chemotherapy, which compares well with rates for the traditional treatment. However these children all had special genetic traits that made their tumors susceptible to the biological agent.

Nai-Kong Cheung, head of the neuroblastoma program at New York's Memorial Sloan-Kettering Cancer Center an independent observer said this research is a “landmark” for neuroblastoma. Co-author Katherine Matthay of the University of California at San Francisco School of Medicine said that neuroblastoma is an “orphan disease” because of its relatively small number of patients. This means that promising drugs for these diseases often go undeveloped because drug companies are not willing to risk losing money on them.

The study appeared in the Sept. 30 issue of the New England Journal of Medicine.