Primary Outcome Measures:
- Efficacy, as measured by 6-month progression-free survival, of the dose-intense temozolomide treatment schedule [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Toxicity associated with the dose-intense temozolomide treatment schedule as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
- Overall survival [ Designated as safety issue: No ]
OBJECTIVES:
Primary
- Determine the efficacy, as measured by 6-month progression-free survival, of a dose-intense temozolomide treatment schedule in patients with recurrent high-grade glioma.
Secondary
- Assess the toxicities of this dose-intense temozolomide.
- Determine the overall survival of patients treated with this dose-intense schedule.
- Determine whether methylation status of the MGMT gene within patients' tumors predicts greater efficacy (progression-free survival), in patients treated on this protocol.
- Determine whether patients' tumors have functional alterations of the mismatch repair (MMR) system by PCR analysis for microsatellite instability (MSI) and whether such alterations may influence outcome in patients treated on this protocol.
- Determine how initial success with temozolomide may influence outcome in recurrent patients treated on this protocol by evaluating patients progressing after two first-line adjuvant courses of temozolomide, patients progressing within 6 months after the 6th adjuvant course of temozolomide, and patients progressing 6 months after temozolomide is voluntarily discontinued.
OUTLINE: Patients receive oral temozolomide once daily on days 1-7 and days 15-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Formalin-fixed paraffin-embedded tissue blocks or unstained paraffin slides from available surgical samples are evaluated for molecular abnormalities in the tumor, including (but not limited to) MGMT status and microsatellite instability.
After completion of study therapy, patients are followed every 3 months for survival.
PROJECTED ACCRUAL: A total of 40 patients with WHO II grade 4 tumors (glioblastoma multiforme [GBM]) and 20 patients with WHO II grade 3 tumors (non-GBM) will be accrued for this study.