Alternative temozolomide regimens have been proposed to overcome O 6-methylguanine-DNA methyltransferase mediated resistance. We investigated the efficacy and tolerability of 1 week on/1 week off temozolomide (ddTMZ) regimen in a cohort of patients treated with ddTMZ between 2005 and 2011 for the progression of a glioblastoma during or after chemo-radiation with temozolomide or a recurrence of another type of glioma after radiotherapy and at least one line of chemotherapy. Patients received ddTMZ at 100-150 mg/m 2/d (days 1-7 and 15-21 in cycles of 28-days). All patients had a contrast enhancing lesion on MRI and the response was assessed by MRI using the RANO criteria; complete and partial responses were considered objective responses. Fifty-three patients were included. The median number of cycles of ddTMZ was 4 (range 1-12). Eight patients discontinued chemotherapy because of toxicity. Two of 24 patients with a progressive glioblastoma had an objective response; progression free survival at 6 months (PFS-6) in glioblastoma was 29%. Three of the 16 patients with a recurrent WHO grade 2 or 3 astrocytoma or oligodendroglioma or oligo-astrocytoma without combined 1p and 19q loss had an objective response and PFS-6 in these patients was 38%. Four out of the 12 evaluable patients with a recurrent WHO grade 2 or 3 oligodendroglioma or oligo-astrocytoma with combined 1p and 19q loss had an objective response; PFS-6 in these patients was 62%. This study indicates that ddTMZ is safe and effective in recurrent glioma, despite previous temozolomide and/or nitrosourea chemotherapy. Our data do not suggest superior efficacy of this schedule as compared to the standard day 1-5 every 4 weeks schedule.

19q, 1p, Astrocytoma, Brain tumors, Chemotherapy, Dose dense temozolomide, Glioblastoma, Glioma, Oligodendroglioma
dx.doi.org/10.1007/s11060-012-0832-5, hdl.handle.net/1765/62900
Journal of Neuro-Oncology
Department of Pathology

Taal, W, Segers-Van Rijn, J.M.W, Kros, J.M, van Heuvel, I, van der Rijt, C.C.D, Bromberg, J.E.C, … van den Bent, M.J. (2012). Dose dense 1 week on/1 week off temozolomide in recurrent glioma: A retrospective study. Journal of Neuro-Oncology, 108(1), 195–200. doi:10.1007/s11060-012-0832-5