Poor survival for infants with MYCN-amplified metastatic neuroblastoma despite intensified treatment: the International Society of Paediatric Oncology European Neuroblastoma Experience

J Clin Oncol. 2009 Mar 1;27(7):1014-9. doi: 10.1200/JCO.2007.14.5839. Epub 2009 Jan 26.

Abstract

Purpose: To report the results of a prospective, nonrandomized European study on infants with neuroblastoma and MYCN gene amplification.

Patients and methods: Infants with neuroblastoma (stage 2, 3, 4, and 4s) and MYCN gene amplification who were diagnosed between 1999 and 2004 were eligible for enrollment onto the study. After diagnosis, staging, and mandatory biologic studies, induction chemotherapy (IC) with conventional drugs was administered, followed by delayed surgery, megatherapy (busulfan-melphalan as a conditioning regimen), and local radiotherapy.

Results: Of the 46 infants enrolled onto the study, 35 infants were eligible; of these 35 infants, 97% had metastatic spread (24 infants had stage 4, and 10 infants had stage 4s). Two-year overall survival (OS) was 30% (SE, 0.08), with median survival time of 12 months, and 23 deaths due to disease. Two-year, event-free survival (EFS) was 29% (SE, 0.07). The treatment was well tolerated with no deaths as a result of toxicity or severe toxicity. Despite protocol adherence, 30% of the patients who were assessable for response to IC experienced disease progression or did not respond. Stage and high lactate dehydrogenase reached significance in the univariate analysis (P = .028 and .039, respectively for OS; and P = .05 and .031 respectively, for EFS). Ten of 16 patients who received megatherapy are still alive.

Conclusion: Although treatment was well tolerated, survival was poor and our IC failed to achieve a satisfactory response in 30% of our patients. New therapeutic approaches and more intense world-wide collaboration are needed to achieve a cure in this population.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Gene Amplification*
  • Genes, myc*
  • Humans
  • Infant
  • Infant, Newborn
  • Leukapheresis
  • Male
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / pathology
  • Neuroblastoma / secondary
  • Neuroblastoma / therapy
  • Peripheral Blood Stem Cell Transplantation
  • Prospective Studies
  • Survival Analysis
  • Transplantation Conditioning
  • Vincristine / administration & dosage

Substances

  • Vincristine
  • Doxorubicin
  • Cyclophosphamide