title: Stage III neuroblastoma over 1 year of age at diagnosis: improved survival with intensive multimodality therapy including multiple alkylating agents.
abstract: OBJECTIVE
  A nonrandomized, single-arm trial was conducted to assess the efficacy of multimodality therapy including intensive chemotherapy with multiple alkylating agents in the treatment of children with Evans stage III neuroblastoma older than 1 year at diagnosis.
  
  
  METHODS
  Twenty-five patients with a median age of 18 months at diagnosis were treated with multimodality therapy including surgery and chemotherapy using either nitrogen mustard (mechlorethamine), doxorubicin, cisplatin, dacarbazine (DTIC), vincristine, and cyclophosphamide (MADDOC) or cisplatin and cyclophosphamide induction followed by maintenance MADDOC (induction MADDOC) protocols. Sixteen of 25 patients also received radiotherapy to the tumor bed and primary lymph nodes. Event-free survival (EFS) was compared with that reported previously in the literature. N-myc amplification was evaluated prospectively and the Shimada classification was evaluated retrospectively as potential prognostic factors.
  
  
  RESULTS
  We report a 72% EFS (95% confidence interval +/- 18%) with a median follow-up of 85 months. EFS was significantly worse for patients with tumors demonstrating N-myc amplification (P = .018). Patients classified as favorable according to the Shimada system experienced a significantly better EFS (P = .04), but unfavorable patients still maintained a 60% EFS.
  
  
  CONCLUSIONS
  Intensive multimodality treatment including MADDOC and induction MADDOC chemotherapy provides a very good EFS for children older than 1 year who have stage III neuroblastoma. Children classified as favorable according to the Shimada system have a better prognosis. Patients whose tumors demonstrate N-myc amplification have a poor prognosis despite therapy.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
authors.forename: D C
authors.initials: DC
authors.lastname: West
authors.forename: R C
authors.initials: RC
authors.lastname: Shamberger
authors.forename: R M
authors.initials: RM
authors.lastname: Macklis
authors.forename: H P
authors.initials: HP
authors.lastname: Kozakewich
authors.forename: A S
authors.initials: AS
authors.lastname: Wayne
authors.forename: S G
authors.initials: SG
authors.lastname: Kreissman
authors.forename: B R
authors.initials: BR
authors.lastname: Korf
authors.forename: B
authors.initials: B
authors.lastname: Lavally
authors.forename: H E
authors.initials: HE
authors.lastname: Grier
mesh_terms: D000477:Alkylating Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000477:Alkylating Agents