OBJECTIVES:
Primary
* Determine the toxicity and feasibility of adding cyclophosphamide and topotecan to induction therapy in patients with newly diagnosed or progressive high-risk neuroblastoma undergoing autologous peripheral blood stem cell (PBSC) transplantation.
* Determine the feasibility of PBSC mobilization and in vivo PBSC tumor purging in these patients after treatment with this regimen.
Secondary
* Determine tumor response rate in patients treated with this regimen.
* Determine the pharmacokinetics of this regimen in these patients.
* Determine whether topotecan affects cyclophosphamide pharmacokinetics in these patients.
* Correlate host DNA with toxicity and cyclophosphamide and topotecan pharmacokinetics in patients treated with this regimen.
* Determine toxicity in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter study. Patients are stratified according to diagnosis (newly diagnosed vs initially stage 1, 2, or 4S that progressed to stage 4 without interval chemotherapy).
* Induction therapy: Patients receive 6 courses of induction therapy.
* Courses 1 and 2: Patients receive cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 6 and continuing until blood counts recover.
* Course 3: Patients receive etoposide IV over 2 hours on days 1-3, cisplatin IV over 1 hour on days 1-4, and G-CSF SC or IV beginning on day 5 and continuing until blood counts recover.
* Course 4: Patients receive cyclophosphamide IV over 6 hours on day 1 and doxorubicin IV and vincristine IV continuously over 24 hours on days 1-3. Patients also receive G-CSF SC or IV beginning on day 4 and continuing until blood counts recover.
* Course 5: Patients receive etoposide, cisplatin, and G-CSF as in course 3.
* Course 6: Patients receive cyclophosphamide, doxorubicin, vincristine, and G-CSF as in course 4.
Treatment repeats every 21 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
* Consolidation therapy: Within 4-6 weeks after completing induction therapy, patients receive melphalan IV on days -7 to -5 and etoposide IV and carboplatin IV continuously over 24 hours on days -7 to -4.
* Stem cell transplantation: Peripheral blood stem cells are collected after course 2 of induction therapy and infused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover.
* Surgery: After course 5 of induction therapy, patients undergo surgery.
* Radiotherapy: Beginning 28-42 days after transplantation, patients receive 12 fractions of local radiotherapy to all areas of residual soft tissue disease and the primary tumor site, even if completely resected.
* Maintenance therapy: Beginning 66 days after transplantation, patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.
Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 10-29 patients will be accrued for this study within 2 years.
