Long-term results of the combination of the N7 induction chemotherapy and the busulfan-melphalan high dose chemotherapy

Pediatr Blood Cancer. 2014 Jun;61(6):977-81. doi: 10.1002/pbc.24713. Epub 2013 Aug 23.

Abstract

Background: To evaluate long-term survival of the first cohort of stage-4 neuroblastoma patients treated with the N7 induction chemotherapy, surgery of the primary tumor and high-dose chemotherapy (HDC) containing Busulfan-Melphalan (Bu-Mel) followed by autologous stem cell transplantation (ASCT).

Procedure: From 1998 to 1999, 47 children were included in the NB97 trial and treated with induction chemotherapy according to the N7 protocol, followed by surgery of the primary tumor. HDC (Busulfan, 600 mg/m(2) Melphalan, 140 mg/m(2) ) was administered in patients with partial response of metastases with no more than 3 mIBG spots. Radiotherapy was delivered to the primary tumor site when tumors displayed MYCN amplification.

Results: Thirty-nine patients received Bu-Mel (83%): 23 who had achieved complete response (CR) of metastases, 20 after induction treatment and 3 after second-line chemotherapy, and 16 in partial response (PR). The toxicity of the whole treatment was manageable. The main HDC related-toxicity was hepatic veno-occlusive disease grade > 2 occurring in 15% of the patients. The 8-year EFS of the whole cohort was 34% (95% CI, 22-48%). The 8-year EFS of the 39 patients who received Bu-Mel and ASCT was 41% (95% CI, 27-57%). Patients who achieved a CR of metastases at the end of induction chemotherapy had a significantly better outcome than the others (8-year EFS, 52% vs. 20%; P = 0.02).

Conclusions: The long-term results of this first prospective cohort of patients with metastatic disease treated with the N7 induction chemotherapy and HDC (Bu-Mel) confirm published data with stable survival curves but with a longer follow-up.

Keywords: Busulphan-Melphalan; high-dose chemotherapy; neuroblastoma.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Neoplasms / drug therapy
  • Abdominal Neoplasms / surgery
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / administration & dosage
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Consolidation Chemotherapy
  • Disease-Free Survival
  • Follow-Up Studies
  • Gene Amplification
  • Genes, myc
  • Hematopoietic Stem Cell Transplantation
  • Hepatic Veno-Occlusive Disease / chemically induced
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Melphalan / administration & dosage
  • Myeloablative Agonists / therapeutic use
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / secondary
  • Neuroblastoma / surgery
  • Proportional Hazards Models
  • Remission Induction
  • Thoracic Neoplasms / drug therapy
  • Thoracic Neoplasms / surgery
  • Transplantation Conditioning
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Myeloablative Agonists
  • Busulfan
  • Melphalan