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
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
DISEASE CHARACTERISTICS: Neuroblastoma diagnosed in accordance with the International
Neuroblastoma Staging system: Histologic confirmation at MSKCC OR Elevated urinary
catecholamines plus tumor cells/clumps in bone marrow Stage IV or Stage II/III with more
than 10 copies of N-myc proto-oncogene per tumor cell
PATIENT CHARACTERISTICS: See General Eligibility Criteria
PRIOR CONCURRENT THERAPY: Prior therapy allowed -Patient Characteristics-- Age: Over 1
year at diagnosis Performance status: Not specified Hematopoietic: Absolute neutrophil
count at least 500/mm3 (except for cases of bone marrow infiltration by tumor) Platelet
count at least 100,000/mm3 (except for cases of bone marrow infiltration by tumor)
Hepatic: Not specified Renal: Not specified Other: No history of allergy to mouse proteins
Human antimouse antibodies (HAMA) less than 1,000 U/ml (with prior exposure to murine