A randomized Phase III trial showed that children with high-risk neuroblastoma had better event-free and overall survival with a combination of the myeloablative chemotherapy drugs busulphan and melphalan (BuMel) compared to a different myeloablative regimen of three chemotherapy drugs, carboplatin, etoposide and melphalan (CEM). These results establish a new standard of care for children with high-risk disease, of whom previously only 30 percent survive long-term. Myeloablative chemotherapy is high-dose chemotherapy that kills cells in the bone marrow, including cancer cells.

"The study's results are important for patients with this extremely difficult to treat disease," said lead author Ruth Ladenstein, M.D., MBA, associate professor of pediatrics at the University of Vienna and St. Anna Children's Cancer Research Institute in Vienna. "These results, combined with the recent report that an anti-GD2 ch14.18 antibody-based immune therapy can increase event-free and overall survival by 20 percent in high-risk patients, mean that we could potentially improve overall prognosis by up to 35 percent in the future. Thus, we overcome the 50 percent threshold in survival rates by choosing the right high-dose myeloablative regimen for these patients."

Neuroblastoma is a rare cancer of specialized nerve cells, but it is the most common cancer in the first year of life and accounts for approximately 15 percent of childhood cancer deaths. About 650 cases are diagnosed each year in the United States, with about 40 percent that are considered high-risk, meaning they are very likely to recur or progress, despite therapy. The typical therapy for these patients includes intense upfront chemotherapy to induce remission, surgery, radiotherapy, myeloablative therapy to kill the cancer cells remaining in the bone marrow combined with stem cell transplantation, and followed by minimal residual disease treatment with 13 cis retinoid acid, as well as immunotherapy if available.

The HR-NLB1 trial of the European SIOP Neuroblastoma Group compared the effectiveness of two high-dose myeloablative chemotherapy regimens. In the trial, 563 children (median age three) with stage IV, high-risk disease with distant metastases or local disease with MYCN oncogene amplification were randomized to receive either BuMel (281) or CEM (282). After three years, the event-free survival for BuMel was 49 percent compared to 33 percent for the CEM group. The overall survival after three years was 60 percent for those who received BuMel compared to 48 percent in the CEM group without immunotherapy, and the busulphan group had lower rates of relapse and progression (47 percent versus 60 percent). Based on the results, the randomization was stopped early.

Treatment for neuroblastoma is not without risk. The treatment-related death rate was 3 percent for the busulphan regimen and 5 percent for CEM.