Trial Information

Comparison of High Dose Rapid Schedule With Conventional Schedule Chemotherapy for Stage 4 Neuroblastoma Over the Age of One Year

OBJECTIVES:

- Compare the response rates (bone marrow and primary tumor) in young patients with
disseminated neuroblastoma treated with two different combination chemotherapy
schedules comprising vincristine, cyclophosphamide, cisplatin, etoposide, and
carboplatin followed by surgery and autologous stem cell transplantation.

- Compare the event-free survival of patients treated with these regimens.

- Compare the prognostic factors of patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2
treatment arms.

- Arm I (OPEC/OJEC): Patients receive OPEC combination chemotherapy comprising
vincristine IV, cyclophosphamide IV, cisplatin IV continuously over 24 hours, and
etoposide IV over 4 hours on day 1 of course 1. Patients then receive OJEC combination
chemotherapy comprising vincristine IV, cyclophosphamide IV, etoposide IV over 4 hours,
and carboplatin IV over 1 hour on day 1 of course 2. OPEC and OJEC regimens alternate
so that patients receive 4 courses of OPEC and 3 courses of OJEC over 18 weeks in the
absence of disease progression or unacceptable toxicity.

- Arm II (Rapid COJEC): Patients receive vincristine IV and carboplatin IV over 1 hour on
day 1 and etoposide IV over 4 hours on days 1 and 2 (regimen 1). Ten days later,
patients receive vincristine IV followed by cisplatin IV continuously over 24 hours on
day 1 (regimen 2). Ten days later, patients receive vincristine IV on day 1 and
etoposide IV over 4 hours and cyclophosphamide IV on days 1 and 2 (regimen 3).
Treatment continues for 10 weeks (with a 10-day interval between regimens in this
order: regimen 2, regimen 1, regimen 2, regimen 3, and regimen 2) in the absence of
disease progression or unacceptable toxicity.

Patients who achieve bone marrow complete remission then undergo surgery. Patients achieving
bone marrow partial remission or less are removed from study.

After surgery, patients receive cyclophosphamide IV on day -7 and undergo bone marrow
harvest on day 1. Patients then receive high-dose melphalan IV on day 1. Autologous bone
marrow cells are reinfused on day 3.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 190 patients will be accrued for this study.