Effect of alternative temozolomide schedules on glioblastoma O(6)-methylguanine-DNA methyltransferase activity and survival.

British Journal of Cancer
C G RobinsonM A Vogelbaum

Abstract

O(6)-methylguanine-DNA methyltransferase (MGMT) expression in glioblastoma correlates with temozolomide resistance. Dose-intense temozolomide schedules deplete MGMT activity in peripheral blood mononuclear cells; however, no published data exist evaluating the effect of temozolomide schedules on intracranial tumour MGMT activity. Human glioblastoma cells (GBM43) with an unmethylated MGMT promoter were implanted intracranially in immunodeficient rodents. Three weeks later, animals received temozolomide 200 mg m(-2) for 5 days (schedule A, standard dose) or 100 mg m(-2) for 21 days (schedule B, dose intense). Tumour MGMT activity was depleted by day 6 in both treatment groups compared with baseline. O(6)-methylguanine-DNA methyltransferase activity returned to baseline by day 22 in the schedule A group, but remained suppressed in the schedule B group. By day 29, MGMT activity had returned to baseline in both groups. Mean tumour volume was significantly decreased compared with untreated controls with either schedule (P<0.01), although neither schedule was superior (P=0.60). Median survival was 64, 42, and 28 days for schedule A, schedule B, and no drug, respectively (P<0.001 A or B vs control, P=NS A vs B). Dose-intense temozolomi...Continue Reading

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Citations

Apr 5, 2013·Neuro-oncology·Andrew D NordenPatrick Y Wen
Jul 22, 2015·Scientific Reports·Katharina FriedleinIlker Y Eyüpoglu
Apr 20, 2018·Pharmacological Reviews·Andrea ShergalisNouri Neamati
Jun 11, 2014·Nano Letters·Tomas OrlandoAlessandro Lascialfari

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