OBJECTIVES:
* Determine the safety of adjuvant irinotecan when administered concurrently with radiotherapy in patients with newly diagnosed glioblastoma multiforme.
* Determine survival of patients treated with this regimen followed by irinotecan and carmustine.
* Assess the toxic effects of this regimen in these patients.
* Determine whether the dose of irinotecan chosen produces radiosensitizing plasma concentrations of SN-38 in these patients.
* Assess individual variation in responses (toxicity and/or activity), pharmacokinetic parameters, and/or biological correlates due to genetic differences in enzymes involved in transport, metabolism, and/or mechanism of action of irinotecan in these patients treated with this regimen.
OUTLINE: This is a pilot, dose-escalation study of irinotecan. Patients are stratified according to receipt of concurrent enzyme-inducing anticonvulsants (EIACs) (yes vs no).
* Phase I (closed to accrual as of 3/5/2005): Patients receive carmustine IV over 2 hours on day 1 of courses 2-5 and irinotecan IV over 90 minutes (beginning immediately after carmustine infusion) on days 1, 8, 22, and 29 of courses 1-5. Patients also undergo radiotherapy 5 days a week for 6 weeks concurrently with course 1 only. Treatment repeats every 6 weeks for 5 courses in the absence of unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of irinotecan until the recommended dose for phase II is determined. The recommended dose for phase II is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity.
