title: Disseminated neuroblastoma in children older than one year at diagnosis: comparable results with three consecutive high-dose protocols adopted by the Italian Co-Operative Group for Neuroblastoma.
abstract: OBJECTIVE
  To compare the outcomes associated with modifications in three consecutive protocols employed by the Italian Co-Operative Group for Neuroblastoma (ICGNB) in disseminated neuroblastoma.
  
  
  METHODS
  Between January 1985 and November 1997, a total of 359 children aged 1 to 15 years with newly diagnosed stage 4 neuroblastoma were enrolled in three consecutive protocols. Compared with ICGNB-85, the ICGNB-89 protocol contained two more chemotherapy cycles, and some drugs were given at greater doses, whereas in the ICGNB-92 protocol, the induction phase included a chelating agent, and individual cycles contained four drugs instead of two.
  
  
  RESULTS
  A total of 330 of 359 evaluable children were included in this analysis; 106 children were treated with ICGNB-85, 65 children were treated with ICGNB-89, and 159 children were treated with ICGNB-92 protocols. Radical resection of primary tumor was carried out in 59.4%, 50.8%, and 57.9% of the patients, respectively. Major tumor response after induction therapy was achieved in 66.7%, 69.2%, and 68.6% of the patients, respectively. A total of 218 of 232 patients received consolidation therapy consisting of conventional chemotherapy in 65 patients and of high-dose chemotherapy in 153 patients. Disease recurrence or progression occurred in 82.1%, 69.2%, and 74.8% of the patients, respectively. Therapy-related deaths occurred in 1.9%, 12.3%, and 6.9% of the patients, respectively. Five-year overall survival (OS) for the three studies was 26%, 23%, and 28%, and event-free survival (EFS) was 19%, 17%, and 17%, respectively.
  
  
  CONCLUSIONS
  The therapeutic modifications adopted in the ICGNB-89 and ICGNB-92 protocols were not associated with a significant improvement in response rate or in the 5-year OS and EFS as compared with the ICGNB-85 protocol. Attempts at intensifying chemotherapy were associated with greater toxicity.
authors.affiliation: Giannina Gaslini Children's Hospital, Largo Gerolamo Gaslini 5, 16147 Genova, Italy. brunodebernardi@ospedale-gaslini.ge.it
authors.forename: Bruno
authors.initials: B
authors.lastname: De Bernardi
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nicolas
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.forename: Paolo
authors.initials: P
authors.lastname: Indolfi
authors.forename: Modesto
authors.initials: M
authors.lastname: Carli
authors.forename: Luca
authors.initials: L
authors.lastname: Cordero Di Montezemolo
authors.forename: Alberto
authors.initials: A
authors.lastname: Donfrancesco
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Massimo
authors.initials: M
authors.lastname: Provenzi
authors.forename: Andrea
authors.initials: A
authors.lastname: di Cataldo
authors.forename: Antonino
authors.initials: A
authors.lastname: Rizzo
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Tonini
authors.forename: Sandro
authors.initials: S
authors.lastname: Dallorso
authors.forename: Massimo
authors.initials: M
authors.lastname: Conte
authors.forename: Claudio
authors.initials: C
authors.lastname: Gambini
authors.forename: Alberto
authors.initials: A
authors.lastname: Garaventa
authors.forename: Federico
authors.initials: F
authors.lastname: Bonetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanazzo
authors.forename: Paolo
authors.initials: P
authors.lastname: D'Angelo
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D009447:Neuroblastoma / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D010440:Peptichemio / Q000008:administration & dosage; D012189:Retrospective Studies; D016019:Survival Analysis; D013713:Teniposide / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D010440:Peptichemio; D013713:Teniposide; D002945:Cisplatin