N8: Dose-Intensive Chemotherapy Plus Biologics in the Treatment of Neuroblastoma

OBJECTIVES:

• Determine whether treatment with multimodality therapy comprising dose-intensive induction chemotherapy, monoclonal antibody 3F8, surgery, myeloablative chemotherapy, autologous or syngeneic bone marrow or peripheral blood stem cell transplantation, radiotherapy, and isotretinoin improves the cure rate in patients with advanced neuroblastoma.
• Determine whether the 2-year progression-free survival (PFS) rate improves to 70% in patients with newly diagnosed advanced neuroblastoma treated with this regimen.
• Determine whether the 2-year PFS rate improves to 40% in patients with previously treated advanced neuroblastoma treated with this regimen.
• Determine the biologic and clinical prognostic factors of neuroblastoma that may guide future research of treatment approaches for this malignancy.

OUTLINE: Patients are stratified according to the following:

• Stratum 1: Patients with previously untreated stage IV disease who are over age 1 at diagnosis, with or without N-myc amplification
• Stratum 2: Patients with previously treated stage IV disease who are over age 1 at diagnosis; or patients with previously treated high-risk disease (e.g., N-myc amplified stage III or IV disease, under age 1 at diagnosis, and with or without prior treatment)
• Intensive induction therapy (courses 1-5): During courses 1, 2, and 4, patients receive cyclophosphamide IV over 6 hours on days 1 and 2 and doxorubicin and vincristine IV continuously on days 1-3. Courses repeat every 21 days. During courses 3 and 5, patients receive etoposide (VP-16) IV over 2 hours on days 1-3 and cisplatin IV over 1 hour on days 1-4. Courses repeat every 35 days. Before proceeding to myeloablative therapy/transplantation, patients in stratum 2 must have received a minimum of 2 courses of chemotherapy if they achieved a complete response (CR) or very good partial response (VGPR) or patients must have received a minimum of 3 courses of chemotherapy if they achieved less than a CR or VGPR.

Patients undergo tumor resection either at diagnosis or after completion of a minimum of 3 courses of chemotherapy (approximately day 63).