Radiation Therapy, Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Primitive Neuroectodermal Tumors

Brain and Central Nervous System Tumors, Neuroblastoma

regional neuroblastoma, disseminated neuroblastoma, stage 4S neuroblastoma, untreated childhood supratentorial primitive neuroectodermal tumor, untreated childhood medulloblastoma, newly diagnosed childhood ependymoma

RATIONALE: Radiation therapy uses x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of radiation therapy and chemotherapy and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of radiation therapy, chemotherapy and peripheral stem cell transplantation in treating patients with primitive neuroectodermal tumors.

OBJECTIVES: * Determine the safety of postradiotherapy high-dose consolidation chemotherapy with peripheral blood stem cell (PBSC) support in patients with high-risk primitive neuroectodermal tumors. * Determine the safety of delaying radiotherapy by approximately one month in these patients. * Determine the maximum tolerated dose of thiotepa in these patients. * Determine the toxic effects of intensive chemotherapy with PBSC support in these patients. * Assess the time to hematopoietic recovery after PBSC infusion when intensive chemotherapy is used after craniospinal radiotherapy in these patients. * Determine the overall and event-free survival of patients treated with this regimen. OUTLINE: This is a dose-escalation study of thiotepa during consolidation therapy. * Induction: Within 31 days of initial surgery, patients receive induction therapy comprising vincristine IV on day 0, cyclophosphamide IV over 2 hours on days 0 and 1, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 2 and continuing for at least 7-10 days. Peripheral blood stem cells (PBSC) are then collected. * Chemoradiotherapy: After blood cell counts recover, and within 28 days of starting induction, patients begin chemoradiotherapy. Patients receive vincristine IV once weekly for 8 doses. Radiotherapy is administered 5 days a week, for 6 weeks, beginning within the same week as the start of vincristine. * Consolidation: Therapy begins 4-6 weeks after the last radiation treatment in the absence of disease progression. The first and third course are the same and comprise vincristine IV on day 0, carboplatin IV over 1 hour on days 0 and 1, thiotepa IV over 3 hours on days 2-4, and G-CSF SC daily beginning on day 7. PBSC are reinfused on day 7. The second course comprises vincristine IV on day 0, carboplatin IV over 1 hour on days 0 and 1, cyclophosphamide IV over 2 hours on days 2 and 3, and G-CSF SC daily beginning on day 5. PBSC are reinfused on day 5. Each course lasts 21 days. For consolidation therapy, cohorts of 6-12 patients each receive escalating doses of thiotepa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 12 patients experience dose-limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 24-56 patients will be accrued for this study.

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United States