title: Improved survival for patients with advanced neuroblastoma after high-dose combined chemotherapy based in part on N-myc amplification.
abstract: OBJECTIVE
  In spite of many different kinds of chemotherapy for neuroblastoma, the prognosis for advanced neuroblastoma remains unsatisfactory. In particular, the outcome of advanced neuroblastoma with high copies of the N-myc gene tend to be poor. Therefore, the new high-dosage combined chemotherapy regimens for advanced neuroblastoma based in part on the N-myc amplification status has been utilized in the Kyushu area of Japan since 1991. This study aims to investigate whether these new regimens based in part on N-myc amplification have improved the survival rate of stage III and stage IV patients in comparison with the old regimens.
  
  
  METHODS
  Between 1983 and 1995, 77 patients over 1 year of age and with stage III or IV neuroblastoma were registered in the Kyushu Area. Between 1983 and 1990, 49 patients received 1 of 2 combined chemotherapy regimens consisting of cyclophosphamide, cisplatin plus VM-26, and Adriamycin plus DTIC. Since 1991, two new regimens (New A1 and A3) have been administered based on the N-myc amplification status in a total of 28 patients. The New A1 regimen, which consists of cyclophosphamide, cisplatin, Adriamycin, and VP-16 has been administered in cases of less than 10 copies of N-myc, whereas the A3 regimen, consisting of a higher dose of cyclophosphamide, cisplatin, Adriamycin, and VP-16, has been administered in cases of more than 10 copies of N-myc. The survival rate was then compared between the old regimens and the new regimens.
  
  
  RESULTS
  The 3-year survival rate (61.5%) for patients treated by the new regimens was significantly higher than that (32.7%) for patients treated by the old regimens (P <.01). Regarding the 24 cases of more than 10 copies of N-myc, the 3-year survival rate (35.9%) of the 13 patients treated by the A3 regimen was higher than that (0%) of the 11 patients treated by the old regimens (P <.05). However, in the 19 stage IV patients treated by the new regimens, the 3-year survival rate (11.1%) of the 9 cases of more than 10 copies was significantly lower than that (77.8%) of the 10 cases of less than 10 copies of N-myc (P <.01).
  
  
  CONCLUSIONS
  These results suggest that high-dose combined chemotherapy based in part on the N-myc amplification status significantly improved the prognosis of patients with advanced neuroblastoma. However, stage IV patients with N-myc amplification still require a more effective treatment modality.
authors: Departments of Pediatric Surgery and Pediatrics and Pathology, Kyushu University, Fukuoka, Japan.
authors: S
authors: S
authors: Suita
authors: T
authors: T
authors: Tajiri
authors: Y
authors: Y
authors: Sera
authors: H
authors: H
authors: Takamatsu
authors: H
authors: H
authors: Mizote
authors: A
authors: A
authors: Nagasaki
authors: N
authors: N
authors: Kurosaki
authors: T
authors: T
authors: Hara
authors: J
authors: J
authors: Okamura
authors: S
authors: S
authors: Miyazaki
authors: T
authors: T
authors: Sugimoto
authors: K
authors: K
authors: Kawakami
authors: H
authors: H
authors: Eguchi
authors: M
authors: M
authors: Tsuneyoshi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis