OBJECTIVES:

• Determine the antitumor effects of monoclonal antibody 3F8, etoposide, and isotretinoin using standard imaging methods and tumor marker studies in patients with high-risk neuroblastoma.
• Assess progression-free survival in these patients after this treatment.
• Assess the effects of oral etoposide on human anti-mouse antibody and anti-idiotype response in these patients.

OUTLINE: Patients are stratified according to disease status (evaluable but not measurable vs second or subsequent remission with no measurable or evaluable disease).

Patients receive monoclonal antibody 3F8 (MOAB 3F8) IV over 1.5 hours once daily on days 1-10 and oral etoposide once daily on days 29-49. Treatment repeats every 8 weeks for 4 courses in the absence of disease progression, human anti-mouse antibody (HAMA) response, or unacceptable toxicity.

If HAMA fails to develop after completion of 4 courses of MOAB 3F8, patients continue treatment with MOAB 3F8 on days 1-5 every 8 weeks until HAMA reaches greater than 1,000 U/mL or until month 24, whichever occurs first.

Beginning after completion of 4 courses of etoposide and MOAB 3F8 or if HAMA develops, patients receive oral isotretinoin twice daily for 14 days followed by at least a 14-day rest. Treatment repeats for a total of 6 courses.

PROJECTED ACCRUAL: A total of 50 patients (25 per stratum) will be accrued for this study within 5 years.

DISEASE CHARACTERISTICS:

• High-risk neuroblastoma by:

  • Histopathology OR
  • Bone marrow involvement plus elevated urinary catecholamines

• Prior tumor progression on standard chemotherapy and poor long-term prognosis as indicated by 1 or more of the following:

  • N-myc amplification in tumor cells
  • Diploid chromosomal content plus lp loss of heterozygosity in tumor cells
  • Distant skeletal metastases
  • Unresectable primary tumor infiltrating across the midline
  • More than 10% tumor cells in bone marrow
  • Less than 30% chance of long-term progression-free survival
• Evaluable (microscopic marrow metastasis, elevated tumor markers, abnormal bone scan or MIBG or PET scan) but not measurable (CT scan, MRI) disease documented at least 4 weeks after completion of prior systemic therapy

• No rapidly progressive disease as defined by 1 or more of the following:

  • Serum lactic dehydrogenase greater than 1.5 times upper limit of normal due to tumor
  • An opiate requirement for pain from tumor
  • Greater than 25% increase in tumor by successive imaging studies
  • Life expectancy less than 8 weeks
• Second or subsequent remission after chemotherapy and/or radiotherapy allowed provided there is less than 30% chance of survival
• No prior myelodysplastic syndromes or leukemia

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Not specified

Life expectancy:

• See Disease Characteristics
• At least 8 weeks

Hematopoietic:

• Not specified

Hepatic:

• No grade 3 or worse liver toxicity

Renal:

• No grade 3 or worse renal toxicity
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No grade 3 or worse cardiac toxicity

Pulmonary:

• No grade 3 or worse pulmonary toxicity

Other:

• Not pregnant
• No grade 3 or worse gastrointestinal toxicity
• No grade 3 or worse neurologic system toxicity
• No grade 4 hearing deficit
• No active life-threatening infection
• No prior exposure to mouse antibodies and human anti-mouse antibody greater than 1,000 ELISA units/mL
• No allergy to mouse proteins

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics