Irinotecan in Treating Patients With Recurrent Glioma

OBJECTIVES: I. Determine the efficacy of irinotecan in the treatment of patients with
recurrent glioma. II. Assess the toxicities of irinotecan in these patients. III. Correlate
the pharmacological parameters with toxicity and response to therapy.

OUTLINE: This is a two arm study. Patients are stratified according to prior nitrosourea
administration. Patients are assigned to 1 of 2 arms, with only 1 arm being open at any
time. Patients assigned to arm I receive irinotecan IV over 90 minutes on days 1, 8, 15, and
22. This is followed by a 2 week rest and continues for a maximum of 6 courses. Patients
assigned to arm II receive irinotecan on day 1 every 3 weeks for up to 12 courses. Patients
in both arms who received prior nitrosoureas receive reduced starting doses of irinotecan.
The dosages may be increased once per patient after the first course if toxic effects are
acceptable. Arm I closed as of 10/98, Arm II open as of 10/98. Patients are followed every 3
months for the first year, every 6 months for the next 4 years, then annually until death.

DISEASE CHARACTERISTICS: Histologically proven primary brain glioma Astrocytoma
Gliosarcoma Oligodendroglioma Oligoastrocytoma Tumor progression by CT scan or MRI
following radiotherapy Measurable or evaluable disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy:
Not specified Hematopoietic: Absolute neutrophil count at least 1500/mm3 Platelet count at
least 100,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL
AST no greater than 3 times upper limit of normal No prior Gilbert's syndrome Renal:
Creatinine no greater than 2.0 mg/dL Cardiovascular: No history of myocardial infarction
within 6 months No congestive heart failure requiring therapy Other: No concurrent active
second malignancy No uncontrolled infection No other severe concurrent disease Not
pregnant or lactating Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No more than 1
prior adjuvant chemotherapy regimen and 1 for recurrence (Gliadel is considered 1 regimen)
At least 4 weeks since prior chemotherapy At least 6 weeks since prior nitrosoureas No
prior irinotecan, topotecan, or aminocamptothecin Endocrine therapy: At least 2 weeks on
fixed dose of corticosteroids (or no corticosteroids) prior to baseline scan Radiotherapy:
At least 8 weeks since prior radiotherapy Surgery: No surgical resection between last
radiotherapy or chemotherapy and study therapy, unless unequivocal tumor growth since
surgery