Radiation Therapy, Arsenic Trioxide, and Temozolomide in Treating Patients With Newly Diagnosed High-Grade Glioma

OBJECTIVES:

• Determine the maximum tolerated dose of arsenic trioxide when administered sequentially with temozolomide during radiotherapy in patients with newly diagnosed glioblastoma multiforme.
• 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.

DISEASE CHARACTERISTICS:

• Newly diagnosed grade III or IV glioma including any of the following:

• Glioblastoma
• Anaplastic astrocytoma
• Gliosarcoma
• 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

PATIENT CHARACTERISTICS:

• 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