RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in
chemotherapy, such as arsenic trioxide and temozolomide, work in different ways to stop the
growth of tumor cells, either by killing the cells or by stopping them from dividing.
Arsenic trioxide and temozolomide may also make tumor cells more sensitive to radiation
therapy. Giving radiation therapy together with combination chemotherapy may kill more tumor
PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide
when given together with temozolomide and radiation therapy in treating patients with newly
diagnosed high-grade glioma.
- Determine the maximum tolerated dose of arsenic trioxide when administered sequentially
with temozolomide during radiotherapy in patients with newly diagnosed glioblastoma
- Determine the dose-limiting toxicities of this regimen in these patients.
OUTLINE: This is a dose-escalation study of arsenic trioxide.
Patients undergo radiotherapy (may be intensity-modulated) on days 1-5. Patients also
receive arsenic trioxide IV over 1-2 hours on days 1-5, and oral temozolomide on days 1-7.
Treatment with radiotherapy, arsenic trioxide, and temozolomide repeats every week for up to
6 weeks in the absence of disease progression or unacceptable toxicity.
Patients may then receive oral temozolomide on days 1-5. Treatment repeats every 4 weeks for
up to 12 courses in the absence of disease progression.
After completion of study therapy, patients are followed periodically.
- Newly diagnosed grade III or IV glioma including any of the following:
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Anaplastic oligoastrocytoma
- Measurable or nonmeasurable disease
- No more than 5 weeks since prior brain surgery
- Recovered from surgery, post- operative infection, and other complications
- Preoperatively and postoperatively diagnostic contrast-enhanced MRI or CT scan of the
brain performed prior to radiation therapy
- Patients diagnosed by stereotactic biopsy do not require the postoperative scan
- Karnofsky performance status ≥ 60%
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
- Total bilirubin ≤ 2.0 mg/dL
- AST ≤ 4.0 times ULN
- No prolonged QT interval > 460 milliseconds on baseline electrocardiogram in the
presence of normal serum potassium and magnesium
- No uncontrolled electrolyte imbalance (i.e., sodium < 132 mmol/L, potassium < 3.5
mEq/dL, magnesium < 1.7 mg/dL)
- No history of torsades de pointes type of ventricular arrhythmia
- Negative pregnancy test
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No medical or psychiatric illness that, in the investigator's opinion, could
potentially preclude the completion of study therapy
- No HIV positivity
- No active connective tissue disorders (e.g., lupus or scleroderma) that, in the
investigator's opinion, may put the patient at high risk for radiation toxicity
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior brain radiotherapy or chemotherapy for brain tumor
- Concurrent corticosteroids to control cerebral edema allowed provided dose is stable
or decreasing for the past 5 days
- No concurrent or plan to receive drugs that are known to prolong the QT interval
- No prior radiation to the head or neck (except for T1 glottic cancer) resulting in
overlap of radiation fields