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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

Bruno De Bernardi, Brigitte Nicolas, Luca Boni, Paolo Indolfi, Modesto Carli, Luca Cordero di Montezemolo, Alberto Donfrancesco, Andrea Pession, Massimo Provenzi, Andrea di Cataldo, Antonino Rizzo, Gian Paolo Tonini, Sandro Dallorso, Massimo Conte, Claudio Gambini, Alberto Garaventa, Federico Bonetti, Andrea Zanazzo, Paolo D’Angelo, Paolo Bruzzi

From the Departments of Hematology-Oncology and Surgery, and Service of Pathology, Giannina Gaslini Children’s Hospital; Laboratory for Population Genetics, and Clinical Epidemiology Unit, National Cancer Research Institute, Genova; the Division of Oncology, Bambino Gesù Children’s Hospital, Roma; the Civic Hospital, Bergamo; and the Department of Pediatrics, Universities of Bologna, Brescia, Catania, Napoli, Padova, Palermo, Pavia, Torino, and Trieste, Italy.

Address reprint requests to Bruno De Bernardi, MD, Giannina Gaslini Children’s Hospital, Largo Gerolamo Gaslini 5, 16147 Genova, Italy; email: brunodebernardi{at}ospedale-gaslini.ge.it.

Purpose: To compare the outcomes associated with modifications in three consecutive protocols employed by the Italian Co-Operative Group for Neuroblastoma (ICGNB) in disseminated neuroblastoma.

Patients and 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.

Conclusion: 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.

Supported in part by research grants from the Giannina Gaslini Children’s Hospital and the Italian Neuroblastoma Association, Genova, Italy.

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