Radiation Therapy, Temozolomide, and Irinotecan in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

OBJECTIVES:

• Compare overall survival of patients with newly diagnosed supratentorial glioblastoma multiforme treated with radiotherapy and temozolomide followed by temozolomide and irinotecan with historical controls from the RTOG database.
• Determine the short- and long-term toxicity of this regimen in these patients.
• Determine progression-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Chemoradiotherapy: Patients undergo radiotherapy once daily, 5 days a week, for 6 weeks. Concurrently with radiotherapy, patients receive oral temozolomide once daily, 7 days a week, for 6 weeks.
• Post-radiotherapy chemotherapy: Beginning 4-6 weeks after the completion of chemoradiotherapy, patients receive irinotecan IV on days 1 and 15 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 157 patients will be accrued for this study within 11 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed supratentorial glioblastoma multiforme by surgical biopsy or excision

• No gliomas graded less than glioblastoma multiforme
• No recurrent malignant gliomas
• No tumor foci below the tentorium or beyond the cranial vault
• Study therapy must begin ≤ 5 weeks after surgery

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• At least 8 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL*
• Hematocrit ≥ 30%* NOTE: *Transfusion allowed

Hepatic

• Bilirubin ≤ 0.5 mg/dL
• ALT or AST ≤ 2 times upper limit of normal

Renal

• Creatinine ≤ 1.5 mg/dL
• BUN ≤ 25 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 2 months after study participation
• No AIDS
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder
• No other major medical illness or psychiatric impairment that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent sargramostim (GM-CSF)

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• Concurrent steroid therapy allowed provided patient is on a stable or decreasing dose for at least 2 weeks before study entry

Radiotherapy

• No prior radiotherapy to the head or neck resulting in overlap of radiotherapy fields

• Prior radiotherapy for stage T1 glottic cancer allowed

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• No enzyme-inducing antiepileptic drugs within 14 days before the initiation of irinotecan

• Concurrent non-enzyme-inducing antiepileptic drugs allowed