Chemotherapy, Radiation Therapy, Immunotherapy, and Bone Marrow Transplantation in Treating Patients With Neuroblastoma

Overview

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy, radiation therapy, immunotherapy, and bone marrow transplantation in treating patients with neuroblastoma.

OBJECTIVES: I. Improve the complete remission rate and progression-free survival and reduce the relapse rate of patients with poor-risk neuroblastoma using intensive multimodality therapy: cyclophosphamide/doxorubicin/vincristine and cisplatin/etoposide, external-beam radiotherapy, and surgery (when feasible), followed by radioimmunotherapy with iodine I 131 labeled monoclonal antibody 3F8 followed by autologous bone marrow transplant and immunotherapy with unlabeled 3F8. II. Identify biologic and clinical prognostic factors that may guide future modifications in treatment approaches for this malignancy. OUTLINE: Patients are stratified by prior therapy (yes vs no). Patients undergo surgery either at diagnosis or after at least 4 courses of chemotherapy, then possibly again after completion of chemotherapy. Patients receive cyclophosphamide IV over 6 hours on days 1-2, and doxorubicin IV and vincristine IV over 72 hours on days 1-3 for courses 1, 2, 4, and 6. Cisplatin IV over 1 hour on days 1-4 and vincristine IV over 2 hours on days 1-3 are administered as courses 3, 5, and 7. Courses are administered every 16-21 days. Autologous bone marrow is collected after 3 courses of chemotherapy providing marrow is negative for tumor cells. Patients undergo radiotherapy after the completion of chemotherapy. Radiotherapy is administered twice a day for 7 days. Patients then receive iodine I 131 labeled monoclonal antibody 3F8 (MOAB 3F8) on day -5 and again on days 1-5. Autologous bone marrow is reinfused on day 5 and filgrastim (G-CSF) is administered IV or subcutaneously beginning day 6. Patients who do not develop HAMA or an allergy to mouse proteins receive unlabeled MOAB 3F8 IV over 1.5 hours, 5 days a week for 2 weeks. Treatment repeats every 1-2 months for up to 4 courses. Patients are followed every month for 2 years, every 3 months for 1 year, then annually thereafter. PROJECTED ACCRUAL: Up to 45 newly diagnosed patients will be accrued for this study within 5 years.