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. Chemotherapy combined with radiation therapy may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of temozolomide followed by radiation
therapy in treating children who have newly diagnosed malignant central nervous system
- Determine the response rate to treatment with temozolomide in children with newly
diagnosed malignant central nervous system tumors.
- Determine the toxicity of this treatment in these patients.
- Determine the overall survival in these patients for 18 months following the study
after receiving this treatment.
OUTLINE: Patients are stratified according to type of disease (ependymoma vs brain stem
glioma vs malignant glioma vs other).
Patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for a
maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with a partial or complete response may receive an additional 8 courses of
temozolomide following radiotherapy.
PROJECTED ACCRUAL: A maximum of 100 patients (25 per stratum) will be accrued for this study
over 24-36 months.
- Histologically confirmed newly diagnosed malignant central nervous system tumor not
requiring immediate radiotherapy
- Patients with diffuse pontine tumors do not require histological confirmation
- Eligible types include the following:
- Malignant glioma
- Anaplastic astrocytoma
- Glioblastoma multiforme
- Anaplastic oligodendroglioma
- Anaplastic mixed oligoastrocytoma
- Brainstem glioma
- Primitive neuroectodermal tumor
- Nongerminoma germ cell tumor
- At least one bidimensionally measurable lesion
- At least 1.5 cm2 within 72 hours of surgical resection or greater than 14 days
- Diffuse pontine tumors are not required to be measurable
- Neurologically stable
- 4 to 21
- Karnofsky or Lansky 70-100%
- Greater than 12 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 10 g/dL
- Bilirubin less than 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase less than 2 times ULN
- SGOT and SGPT less than 2.5 times ULN
- BUN and creatinine less than 1.5 times ULN
- Must be able to swallow capsules
- No acute infection treated with intravenous antibiotics
- No nonmalignant systemic disease that makes patient a poor medical risk
- No frequent vomiting or medical condition that may interfere with oral medication
intake (e.g., partial bowel obstruction)
- No other prior or concurrent malignancies except surgically cured carcinoma in situ
of the cervix or basal or squamous cell carcinoma of the skin
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No more than one prior biologic therapy regimen
- No concurrent biologic therapy
- No concurrent growth factors or epoetin alfa
- No more than one prior chemotherapy regimen
- No other concurrent chemotherapy
- No increasing doses of steroids within one week of study
- See Disease Characteristics
- No concurrent radiotherapy
- At least 2 weeks, but no greater than 4 weeks, since prior surgical resection and
- No other concurrent investigational drugs