Temozolomide for High Grade Glioma

Abstract

High grade glioma (HGG) is an aggressive form of brain tumour the treatment of which usually entails biopsy or resection where possible followed by radiotherapy. Temozolomide is a novel oral chemotherapeutic drug that penetrates into the brain and has a low incidence of adverse effects. To assess whether temozolomide holds any advantage over conventional therapy for HGG in either primary or recurrent disease settings. The following databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2007. Medline, EMBASE, Science Citation Index, Physician Data Query and the Meta-Register of Controlled Trials. Reference lists of identified studies were searched. The Journal of Neuro-Oncology was hand searched from 1999 to 2007 including conference abstracts. Neuro-oncologists were contacted regarding ongoing and unpublished trials. Randomised controlled trials (RCTs). Interventions included the use of temozolomide during primary therapy or for recurrent disease. Patients included those of all ages with a proven pathological diagnosis of HGG. Quality assessment and data extraction were undertaken by two review authors. Outcome measures included survival, time to progression, quality of life (QOL) and adverse events. In primary disease two RCTs were identified, enrolling a total of 703 patients, that investigated concomitant and adjuvant temozolomide in Glioblastoma Multiforme (GBM). Temozolomide increased survival (hazard ratio (HR) 0.84, confidence interval (CI) 0.50 to 0.68, p < 0.001) and an increase in time to progression (HR 0.52 CI 0.42 to 0.64 p < 0.0001). This was without having a statistically significant negative effect on QOL and with a low incidence of early adverse events. Grade 3/4 haematological toxicity was found in 5 to14%. The long term effects of temozolomide are still to be assessed. In recurrent GBM a single trial enrolling 225 patients in total found that temozolomide did not increase overall survival but it did increase time to progression (HR 0.68 CI 0.51 to 0.90 p0.008). Severe adverse events were low in this setting. Temozolomide is an effective therapy in GBM for prolonging survival and delaying progression as part of primary therapy without impacting on QoL and with a low incidence of early adverse events. The frequency and severity of late adverse events is unknown. In recurrent GBM it improves time to progression but not overall survival. These findings are from three good quality but non-blinded RCTs of over 900 patients in total.