Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas
Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas
RATIONALE: 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.

 PURPOSE: 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.
OBJECTIVES:

 -  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.

 -  Determine the toxicity of this regimen in these patients.

 -  Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with
 this regimen.

 -  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.

 PROJECTED ACCRUAL: A total of 50-100 patients will be accrued for this study within 1-1.5
 years.
DISEASE CHARACTERISTICS:

 -  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

 PATIENT CHARACTERISTICS:

 Age

 -  3 to 21

 Performance status

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

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

 Life expectancy

 -  At least 8 weeks

 Hematopoietic

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

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

 -  Hemoglobin ≥ 8 g/dL (transfusions allowed)

 Hepatic

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

 -  ALT ≤ 2.5 times ULN

 -  Albumin ≥ 2 g/dL

 Renal

 -  Creatinine ≤ 1.5 times ULN OR

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

 Pulmonary

 -  No evidence of dyspnea at rest

 -  No exercise intolerance

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

 Other

 -  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

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  No prior biologic agents

 Chemotherapy

 -  No prior chemotherapy

 Endocrine therapy

 -  Prior corticosteroids allowed

 -  No concurrent corticosteroids as an antiemetic

 -  Concurrent corticosteroids allowed only for treatment of increased intracranial
 pressure

 Radiotherapy

 -  No concurrent radiotherapy using cobalt-60

 Surgery

 -  See Disease Characteristics

 Other

 -  No other prior treatment

 -  No concurrent phenobarbital or cimetidine

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