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.

DISEASE CHARACTERISTICS:

• Histologically proven primitive neuroectodermal tumor (PNET) of one of the following types:

• Atypical teratoid/rhabdoid tumor
• Medulloblastoma
• Desmoplastic medulloblastoma
• Ependymoblastoma
• Medullomyoblastoma
• Spongioblastoma
• Spongioblastoma polare
• Primitive polar spongioblastoma
• Medulloepithelioma
• Neuroblastoma
• Pineoblastoma
• Posterior fossa PNET must be M1-3 or M0 with greater than 1.5 cm2 residual disease
• Non posterior fossa PNET and other types must be M0-3

• If M3, must show clear evidence of tumor on MRI
• No marrow involvement or other extraneural metastases
• No M4 disease
• No cord compression requiring emergency radiotherapy

PATIENT CHARACTERISTICS:

Age:

• 3 to 21

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 150,000/mm^3 (no platelet transfusions)
• Hemoglobin at least 10 g/dL (red blood cell transfusions allowed)

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST or ALT less than 2.5 times ULN

Renal:

• Creatinine clearance or glomerular filtration rate at least 70 mL/min

Cardiovascular:

• Shortening fraction greater than 27% by echocardiogram OR
• Ejection fraction greater than 47% by MUGA

Pulmonary:

• FEV_1/FVC greater than 60% except for children who:

• Are uncooperative
• Have no dyspnea at rest
• Have no exercise intolerance
• Have pulse oximetry greater than 94% on room air

Other:

• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Steroids for increased intracranial pressure allowed

Radiotherapy:

• See Disease Characteristics
• No prior urgent radiotherapy

Surgery:

• Not specified

Other:

• No prior therapy for tumor