Efficacy of protracted temozolomide dosing is limited in MGMT unmethylated GBM xenograft models

Efficacy of protracted temozolomide dosing is limited in MGMT unmethylated GBM xenograft models.

BACKGROUND Temozolomide (TMZ) is important chemotherapy for glioblastoma multiforme (GBM), but the optimal dosing schedule is unclear. METHODS The efficacies of different clinically relevant dosing regimens were compared in a panel of 7 primary GBM xenografts in an intracranial therapy evaluation model. RESULTS Protracted TMZ therapy (TMZ daily M-F, 3 wk every 4) provided superior survival ...

Temozolomide and MGMT forever?

Is protracted low-dose temozolomide feasible in glioma patients?

The authors investigated the safety of 75 mg/m2 temozolomide for 21 days every 28 days in glioma patients. This schedule could lead to DNA repair enzyme O6-alkylguanine-DNA alkyltransferase depletion, contributing to overcoming drug resistance. Although Phase III studies are forthcoming, no data are available on the long-term toxicity of temozolomide, which, in this series, incurred prolonged, ...

Phase II study of dose-intense temozolomide in recurrent glioblastoma.

2038 Background: Most GBM patients relapse within 1 year from diagnosis. Among patients who progress on standard temozolomide, the optimal therapy is unknown. Resistance to temozolomide is partially mediated by the DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT). Since MGMT may be depleted by prolonged temozolomide administration, dose-intense schedules may overcome resistance ...

Effect of Bevacizumab Plus Temozolomide-Radiotherapy for Newly Diagnosed Glioblastoma with Different MGMT Methylation Status: A Meta-Analysis of Clinical Trials

BACKGROUND MGMT methylation status can influence the therapeutic effect and prognosis of glioblastoma (GBM). There are conflicting results from studies evaluating the efficacy of bevacizumab (BV) when it is combined with temozolomide (TMZ) and radiotherapy (RT) in patients diagnosed with GBM with different MGMT methylation status. MATERIAL AND METHODS Data were extracted from publications in Pu...