Treatment with temozolomide for malignant gliomas: Is rechallenge with alternative dosing regimens successful?

Abstract

11514 Background: Temozolomide (TMZ) is an alkylating agent with activity against malignant gliomas. A variety of dosing schedules has been used including: 5 days on/21 days off (200 mg/m2/d), bid dosing (initial bolus of 200 mg/m2 followed by bid dosing of 90 mg/m2 × 9 doses), and 7 days on/7 days off (150 mg/m2/d). It is not known which regimens are the most effective. Furthermore, it is not known whether patients failing one schedule will respond to alternative ones. Materials and Methods: We report on a retrospective series of 8 patients (7 M, 1 F), who were treated with TMZ at least twice. Mean age at recurrence was 48 (26–58). Pathology revealed GBM (3), AA (4), and AO (1). 7 patients had received prior XRT. 7 patients had a local (L) recurrence at the time of retreatment with TMZ, and one patient had leptomeningeal (LM) and L recurrence. 7 pts received TMZ alone both at the time of the first recurrence and at the time of rechallenge. One patient had received TMZ concommitant with XRT and TMZ alone at the time of rechallenge. Results: See Table . Toxicity was mild and not different than that seen in patients treated with the first course of TMZ. Conclusions: While the number of patients is limited, some observations can be made: 1) patients can respond to TMZ at rechallenge, particularly if a prior response to TMZ had been observed. 2) Some patients who fail or respond modestly to one regimen may achieve a better response to alternative dosing schedules. Further studies need to address whether one regimen of TMZ given at rechallenge allows an improved survival as compared with other regimens without sacrificing safety. [Table: see text] [Table: see text]