title: Excellent outcome with reduced treatment in infants with nonmetastatic and unresectable neuroblastoma without MYCN amplification: results of the prospective INES 99.1.
abstract: OBJECTIVE
  To evaluate the efficacy of low-dose chemotherapy in infants with nonmetastatic and unresectable neuroblastoma (NB) without MYCN amplification.
  
  
  METHODS
  Infants with localized NB and no MYCN amplification were eligible in the SIOPEN Infant Neuroblastoma European Study 99.1 study. Primary tumor was deemed unresectable according to imaging defined risk factors. Diagnostic procedures and staging were carried out according to International Staging System recommendations. Children without threatening symptoms received low-dose cyclophosphamide (5 mg/kg/d × 5 days) and vincristine (0.05 mg/kg at day 1; CyV), repeated once to three times every 2 weeks until surgical excision could be safely performed. Children with either one threatening symptom or insufficient response to CyV were given carboplatin and etoposide (CaE), sometimes followed by vincristine, cyclophosphamide, and doxorubicin. No postoperative treatment was to be administered.
  
  
  RESULTS
  Between December 1999 and April 2004, 120 infants were included in the study. Eighty-eight had no threatening symptoms and 79 received CyV. CaE was given to 49 of them because of insufficient response. Thirty-two children had threatening symptoms, 30 of whom received CaE. Anthracyclines were given to 46 children. Surgery was attempted in 102 patients, leading to gross surgical excision in 93. Relapse occurred in 12 patients (nine local and three metastatic). Five-year overall and event-free survivals were 99% ± 1% and 90% ± 3%, respectively, with a median follow-up of 6.1 years (range, 1.6 to 9.1).
  
  
  CONCLUSIONS
  Low-dose chemotherapy without anthracyclines is effective in 62% of infants with an unresectable NB and no MYCN amplification, allowing excellent survival rates without jeopardizing their long-term outcome.
authors.affiliation: Unité d'Hémato-Oncologie, Hôpital des Enfants, Toulouse, France. rubie.h@chu-toulouse.fr
authors.forename: Hervé
authors.initials: H
authors.lastname: Rubie
authors.forename: Bruno
authors.initials: B
authors.lastname: De Bernardi
authors.forename: Mary
authors.initials: M
authors.lastname: Gerrard
authors.forename: Adela
authors.initials: A
authors.lastname: Canete
authors.forename: Ruth
authors.initials: R
authors.lastname: Ladenstein
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.forename: Peter
authors.initials: P
authors.lastname: Ambros
authors.forename: Caroline
authors.initials: C
authors.lastname: Munzer
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.forename: Alberto
authors.initials: A
authors.lastname: Garaventa
authors.forename: Penelope
authors.initials: P
authors.lastname: Brock
authors.forename: Victoria
authors.initials: V
authors.lastname: Castel
authors.forename: Dominique
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: Keith
authors.initials: K
authors.lastname: Holmes
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Cataldo
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Brichard
authors.forename: Véronique
authors.initials: V
authors.lastname: Mosseri
authors.forename: Catalina
authors.initials: C
authors.lastname: Marquez
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000601:surgery; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins