Rechallenge with temozolomide in recurrent glioma

Abstract

Despite a confirmed survival benefit associated with adjuvant radio- and chemotherapy, the majority of patients with malignant glioma relapse after initial therapy. Recurrent malignant glioma treatment has not been standardised and usually the response rate to standard chemotherapy protocols for recurrent malignant glioma is less than 30%. The growing body of evidence demonstrating the clinical importance of O6-methylguanine methyltransferase (MGMT) has generated a considerable interest in the exploration of strategies to overcome MGMT-mediated resistance to alkylating agents; for example protracted administration of Temozolomide (TMZ) may result in more extensive and sustained depletion of MGMT; for this reason a variety of dosing schedules that increase the duration of exposure and the cumulative dose of TMZ are being investigated for the treatment of patient with recurrent malignant glioma after standard treatment. The most widely studied regimens in this setting include (1) 21 of 28-day schedule at a dose of 75–100 mg/m²/day; (2) 7 of 14-day schedule at a dose of 150 mg/m²/day, also referred to as the ‘‘one week on/one week off’’ schedule; (3) Continuous daily schedule at a dose of 50 mg/m²/day. An alternative dosing schedule of TMZ may be a reasonable option in patients having high-grade gliomas with recurrence after standard therapy.