Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors

OBJECTIVES:

• Determine the maximum tolerated dose of thiotepa in infants with malignant brain or spinal cord tumors receiving intensive chemotherapy.
• Determine the feasibility and toxicity of intensive chemotherapy with peripheral blood stem cell (PBSC) rescue in these patients.
• Assess the feasibility of harvesting PBSCs in these patients.
• Determine the complete response rate and overall event-free survival rate in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Patients undergo surgery for diagnosis and maximal tumor resection.

Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients experiencing dose-limiting toxicity due to thiotepa are removed from the study.

Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 3 years, and then annually for 3 years or until relapse.

PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically proven malignant brain or spinal cord tumor, including the following:

• Primitive neuroectodermal tumor
• Ganglioneuroblastoma
• Medulloblastoma neuroblastoma
• Desmoplastic medulloblastoma
• Medulloepithelioma
• Ependymoma neuroepithelioma
• Anaplastic ependymoma germ cell tumor
• Astrocytoma germinoma
• Anaplastic astrocytoma
• Embryonal carcinoma
• Glioblastoma endodermal sinus tumor
• Gliosarcoma malignant teratoma
• Choroid plexus carcinoma
• Mixed germ cell tumor
• Cerebellar sarcoma
• Pineoblastoma
• Atypical teratoid/rhabdoid tumor
• Choriocarcinoma
• Teratoma (malignant or with malignant transformations)
• Diffusely involved brain stem tumors allowed if there is evidence of brain stem glioma by CT scan or MRI

PATIENT CHARACTERISTICS:

Age:

• 6 months to less than 3 years

Performance Status:

• Not specified

Life Expectancy:

• More than 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL

Renal:

• Glomerular filtration rate or creatinine clearance greater than 70 mL/min

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior corticosteroids allowed

Radiotherapy:

• No prior radiotherapy

Surgery:

• No more than 6 weeks since prior surgery
• Recovered from prior surgery (stable)