title: Poor survival for infants with MYCN-amplified metastatic neuroblastoma despite intensified treatment: the International Society of Paediatric Oncology European Neuroblastoma Experience.
abstract: OBJECTIVE
  To report the results of a prospective, nonrandomized European study on infants with neuroblastoma and MYCN gene amplification.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unidad de Oncología Pediátrica, Hospital Infantil La Fe, Avda de Campanar 21, 46009 Valencia, Spain. canyete_ade@gva.es
authors.forename: Adela
authors.initials: A
authors.lastname: Canete
authors.forename: Mary
authors.initials: M
authors.lastname: Gerrard
authors.forename: Hervé
authors.initials: H
authors.lastname: Rubie
authors.forename: Victoria
authors.initials: V
authors.lastname: Castel
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Cataldo
authors.forename: Caroline
authors.initials: C
authors.lastname: Munzer
authors.forename: Ruth
authors.initials: R
authors.lastname: Ladenstein
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Brichard
authors.forename: José D
authors.initials: JD
authors.lastname: Bermúdez
authors.forename: Jerôme
authors.initials: J
authors.lastname: Couturier
authors.forename: Bruno
authors.initials: B
authors.lastname: de Bernardi
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pearson
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007937:Leukapheresis; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide