A new regimen of oral busulfan (Myleran) and melphalan (Alkeran) extended event-free survival over a regimen of carboplatin (Paraplatin), etoposide (Eposin), and melphalan (CEM) in a phase 3 clinical trial of patients with high-risk pediatric neuroblastoma.
The trial was terminated early once the superiority of the busulfan-melphalan myeloablative regimen became evident, said lead investigator Ruth Ladenstein, MD, Associate Professor of Pediatrics, University of Vienna, and St Anna Children’s Cancer Research Institute, Vienna.
The standard practice should now be the busulfan-melphalan combination for children with high-risk disease in whom the long-term survival rate was <40% before this regimen. “The study’s results are important for patients with this extremely difficult-to-treat disease,” said Dr Ladenstein. “These results...mean that we could potentially improve overall prognosis by up to 35%. We overcome the 50% threshold in survival rates by choosing the right high-dose myeloablative regimen for these patients.” Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of all childhood cancer deaths. The study included 563 patients (median age, 3 years) with stage IV, high-risk disease with distant metastases or local disease with MYCN oncogene amplification. All patients received a rapid induction regimen.
They were then randomized to busulfan and melphalan or the CEM regimen. After a median follow-up of 3.5 years, the event-free survival rate was 49% in the busulfan-melphalan group versus 33% in the CEM group. Randomization was stopped early at an interim analysis. The busulfan-melphalan advantage was consistent across all disease stages and appeared to be most effective in patients with residual disease.
The 3-year overall survival was 60% with busulfan-melphalan versus 48% with CEM without immunotherapy. The busulfan-melphalan group had a lower relapse rate and progression (47%) than the CEM group (60%). The overall toxicity profile was significantly lower with busulfan-melphalan, despite some exceptions.