This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells.

PRIMARY OBJECTIVES:

I. Compare event-free survival of pediatric patients with newly diagnosed high-grade gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.

II. Determine the toxicity of this regimen in these patients. III. Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen.

IV. Correlate polymorphisms in GSTP1, GSTM1 and GSTT1 genes and GSTP1 protein expression in tumors with survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

CHEMORADIOTHERAPY: Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47.

MAINTENANCE CHEMOTHERAPY: Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

Inclusion Criteria:

• Histologically confirmed, newly diagnosed high-grade glioma of 1 of the following histologies:

  • Anaplastic astrocytoma
  • Glioblastoma multiforme
  • Gliosarcoma

• Primary spinal cord malignant gliomas allowed

• No primary brainstem tumors

• Has undergone surgical resection or biopsy of the tumor within the past 31 days

  • Pre-operative and post-operative brain MRI with and without gadolinium-contrast OR pre-operative and post-operative spine MRI for spinal cord primaries

    • Post-operative MRI not required for patients who undergo biopsy only

• No evidence of neuraxis dissemination

  • Spine MRI and cerebrospinal fluid cytology required only if clinically indicated

• Performance status - Karnofsky 50-100% (for patients > 16 years of age)

• Performance status - Lansky 50-100% (for patients ≤ 16 years of age)

• At least 8 weeks

• Absolute neutrophil count ≥ 1,000/mm^3

• Platelet count ≥ 100,000/mm^3 (transfusion independent)

• Hemoglobin ≥ 8 g/dL (transfusions allowed)

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT ≤ 2.5 times ULN

• Albumin ≥ 2 g/dL

• Creatinine ≤ 1.5 times ULN

• Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal

• No evidence of dyspnea at rest

• No exercise intolerance

• Pulse oximetry ≥ 94% (if determination is clinically indicated)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 2 months after study participation

• Able to swallow oral medication

• Seizures allowed provided they are well controlled with anticonvulsants

• No hypersensitivity to temozolomide

• No prior biologic agents

• No prior chemotherapy

• Prior corticosteroids allowed

• No concurrent corticosteroids as an antiemetic

• Concurrent corticosteroids allowed only for treatment of increased intracranial pressure

• No concurrent radiotherapy using cobalt-60

• See Disease Characteristics

• No other prior treatment

• No concurrent phenobarbital or cimetidine

• No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy