title: Standard-dose and high-dose peptichemio and cisplatin in children with disseminated poor-risk neuroblastoma: two studies by the Italian Cooperative Group for Neuroblastoma.
abstract: OBJECTIVE
  The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor-risk neuroblastoma.
  
  
  METHODS
  From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT).
  
  
  RESULTS
  Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5).
  
  
  CONCLUSIONS
  Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established.
authors.affiliation: Department of Hematology-Oncology, Giannina Gaslini Children's Hospital, Genova, Italy.
authors.forename: B
authors.initials: B
authors.lastname: De Bernardi
authors.forename: M
authors.initials: M
authors.lastname: Carli
authors.forename: F
authors.initials: F
authors.lastname: Casale
authors.forename: P
authors.initials: P
authors.lastname: Corciulo
authors.forename: L
authors.initials: L
authors.lastname: Cordero di Montezemolo
authors.forename: C
authors.initials: C
authors.lastname: De Laurentis
authors.forename: S
authors.initials: S
authors.lastname: Bagnulo
authors.forename: M
authors.initials: M
authors.lastname: Brisigotti
authors.forename: N
authors.initials: N
authors.lastname: Marchese
authors.forename: A
authors.initials: A
authors.lastname: Garaventa
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000556:secondary; D010440:Peptichemio / Q000008:administration & dosage; D013223:Statistics as Topic; D016896:Treatment Outcome
chemical_list: D010440:Peptichemio; D002945:Cisplatin