Combination Chemotherapy Plus Radiation Therapy in Treating Adult Patients With Brain Cancer

A Phase II Trial of Preradiation Multiagent Chemotherapy for Adults With "Poor Risk" Medulloblastoma, PNET, and Disseminated Ependymoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one drug and combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by radiation therapy in treating adult patients with brain cancer.

OBJECTIVES:

• Determine the complete and partial response rate of patients with adult medulloblastoma, primitive neuroectodermal tumor, or disseminated ependymoma treated with preradiation combination chemotherapy.
• Determine the progression free survival and overall survival of these adult patients treated with combination chemotherapy followed by craniospinal radiation.
• Determine the toxic effects associated with this treatment in these patients.

OUTLINE: Patients receive cisplatin IV over 6 hours, etoposide IV, and vincristine IV over 1-2 minutes on day 1; etoposide IV and cyclophosphamide IV over 1-2 hours on days 2-3; filgrastim (G-CSF) subcutaneously (SC) on days 4-13; and vincristine IV over 1-2 minutes on day 15. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Within 4-6 weeks after the last chemotherapy course, patients undergo radiotherapy 5 days a week for 6 to 7 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5-10 years.

PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed central nervous system cancer including:

  • Medulloblastoma with either local residual disease of greater than 1 cm^2 on MRI following resection or evidence of metastases (M1-4)
  • Other primitive neuroectodermal tumors
  • Ependymoma with evidence of subarachnoid metastases

• Must have less than 1 cm of midline shift or no acute elevated intercranial pressure

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 4,000/mm^3
• Platelet count greater than 125,000/mm^3
• Hemoglobin greater than 10 g/dL
• No preexisting hematologic condition that would increase toxicity or limit ability to comply with evaluations and follow-up

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)
• SGOT less than 2 times ULN
• Alkaline phosphatase less than 2 times ULN
• No preexisting hepatic condition that would increase toxicity or limit ability to comply with evaluations and follow-up

Renal:

• Creatinine greater than 70 mL/min
• No preexisting renal condition that would increase toxicity or limit ability to comply with evaluations and follow-up

Pulmonary:

• No history of significant pulmonary disease or, if there is preexisting pulmonary disease, then DLCO greater than 60% of predicted
• No preexisting pulmonary condition that would increase toxicity or limit ability to comply with evaluations and follow-up

Other:

• No preexisting psychiatric condition that would increase toxicity or limit ability to comply with evaluations and follow-up
• No prior or concurrent malignancies within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• No increasing doses of steroids for intracranial disease within 3 days of registration

Radiotherapy:

• No prior radiotherapy

Surgery:

• 10-28 days since prior surgical resection OR
• At least 5 days since prior biopsy