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.
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.
De Bernardi
Bruno
B
Giannina Gaslini Children's Hospital, Largo Gerolamo Gaslini 5, 16147 Genova, Italy. brunodebernardi@ospedale-gaslini.ge.it
Nicolas
Brigitte
B
Boni
Luca
L
Indolfi
Paolo
P
Carli
Modesto
M
Cordero Di Montezemolo
Luca
L
Donfrancesco
Alberto
A
Pession
Andrea
A
Provenzi
Massimo
M
di Cataldo
Andrea
A
Rizzo
Antonino
A
Tonini
Gian Paolo
GP
Dallorso
Sandro
S
Conte
Massimo
M
Gambini
Claudio
C
Garaventa
Alberto
A
Bonetti
Federico
F
Zanazzo
Andrea
A
D'Angelo
Paolo
P
Bruzzi
Paolo
P
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
D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D010440:Peptichemio; D013713:Teniposide; D002945:Cisplatin