Temozolomide for the treatment of recurrent glioma: Results of a compassionate use program in Belgium

Abstract

1541 Background: Temozolomide (TMZ) is an oral alkylating agent that has demonstrated objective activity and an acceptable toxicity profile for the treatment of recurrent high-grade gliomas in phase II trials. Only limited information is available on the activity and toxicity of TMZ when prescribed outside a clinical trial. Methods: We conducted a retrospective study to evaluate the activity and safety of TMZ that was prescribed for the treatment of recurrent glioma in the context of a compassionate use program in Belgium. Data were obtained on 117 adult patients (from 5 hospitals) who received TMZ as first or second line chemotherapy. The recommended starting dose of TMZ was 200 mg/m2 x5d q28d for chemonaïve patients and 150 mg/m2 x5d q28d for pretreated patients. Results: Toxicity was generally mild although grade 3/4 toxicity was observed in 22 % of patients. Thrombocytopenia was the most frequent encountered toxicity (grade 3/4 in 17% of patients) and its occurrence was correlated with a starting dose of 200 mg/m2/d. The overall RR (CR + PR) was 29% and 34 % of patients achieved a SD. The median PFS was 104 days (95% CI 85–123) and the median OS was 215 days (95% CI 161–269). In multivariate analysis a “deep localization” of the glioma (as opposed to a cortico-subcortical localization) and the preceding history of a low-grade glioma were identified as independent prognostic variables with regard to TTP & OS. Administration of TMZ as first line chemotherapy was an independent prognostic variable for TTP only. Absence of disease progression at the end of TMZ cycle 3 was significantly correlated with a superior overall survival (landmark analysis, P<0.0001). Conclusions: This retrospective study indicates that the reported activity and toxicity profile of TMZ for the treatment of patients with recurrent glioma is reproducible outside the setting of a prospective clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough (Benelux)