A randomized Phase III trial conducted by researchers of the University of Vienna and St. Anna Children?s Cancer Research Institute Vienna, Austria, showed that children with high-risk neuroblastoma, the most common extracranial solid tumor in infancy, 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, presented today at the 47th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, establish a new standard of care for children with high-risk disease, of whom previously only 30% 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, MD, 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% in high-risk patients, mean that we could potentially improve overall prognosis by up to 35% in the future. Thus, we overcome the 50% threshold in survival rates by choosing the right high-dose myeloablative regimen for these patients.?

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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% of childhood cancer deaths. About 650 cases are diagnosed each year in the United States, with about 40% that are considered high-risk, meaning they are very likely to recur or progress, despite therapy.

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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 busulphan-melphalan (281) or CEM (282). After three years, the event-free survival for busulphan-melphalan was 49% compared to 33% for the CEM group. The overall survival after three years was 60% for those who received busulphan-melphalan compared to 48% in the CEM group without immunotherapy, and the busulphan group had lower rates of relapse and progression (47% vs. 60%). Based on the results, the randomization was stopped early.

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

For more information:
Study Authors: Ladenstein RL, Poetschger U, Luksch R, Brock P, Castel V, et al.
Abstract title: Busulphan-melphalan is the superior myeloablative therapy (MAT) for high risk neuroblastoma: Results from the HR-NBL1/SIOPEN trial.
Sunday, June 5, 2011 1:00 PM, CDT
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