Etoposide Plus Radiation Therapy Followed by Combination Chemotherapy in Treating Children With Newly Diagnosed Advanced Medulloblastoma

OBJECTIVES:

• Assess the response rate and toxicity of oral etoposide and radiotherapy in children with newly diagnosed high stage medulloblastoma.
• Compare the response rate and toxicity of these patients to historical control patients registered on POG #9031.
• Estimate the 2-year event-free survival and overall survival of these patients.
• Evaluate the toxicity of dose intensive chemotherapy with oral etoposide, cisplatin, cyclophosphamide, and vincristine following craniospinal irradiation in these patients.

OUTLINE: Patients begin treatment within 1 month of surgery. Patients receive 6 weeks of radiotherapy to the head and spine, with boosts to the posterior fossa and to sites of metastasis. Patients also receive 2 courses of oral etoposide once daily for 3 weeks concurrent with and immediately following radiotherapy (weeks 1-3 and 5-7).

Patients then receive adjuvant chemotherapy consisting of cisplatin IV once every 4 weeks for 3 courses beginning on week 11, oral etoposide daily for 21 days every 4 weeks for 3 courses (weeks 11, 15, and 19), cyclophosphamide IV on days 1 and 2 with filgrastim (G-CSF) SQ daily for at least 10 days every 4 weeks for 8 courses (weeks 23-51), and vincristine IV on days 1, 8, and 15 every 4 weeks for 8 courses (weeks 23-51).

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and annually thereafter.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within about 2 years.

DISEASE CHARACTERISTICS:

• Histologically diagnosed advanced (high grade) childhood medulloblastoma
• Residual disease of at least 1.5 cm2 in size on MRI or CT scan OR
• Evidence of CNS or extraneural metastases

PATIENT CHARACTERISTICS:

Age:

• 3 to 21

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• SGPT less than 5 times normal
• Bilirubin less than 1.5 mg/dL

Renal:

• Creatinine less than 1.7 mg/dL OR
• Creatinine clearance greater than 70 mL/min

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior corticosteroids allowed

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified