Department Neurology/Neuro-oncology Unit, Erasmus MC University Hospital/Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
J Neurooncol. 2012 May;108(1):195-200. doi: 10.1007/s11060-012-0832-5. Epub 2012 Mar 7.
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.
替代替莫唑胺方案已被提出以克服 O(6)-甲基鸟嘌呤-DNA 甲基转移酶介导的耐药性。我们研究了在 2005 年至 2011 年间接受替莫唑胺化疗-放疗期间或之后发生胶质母细胞瘤进展或在放疗后和至少一线化疗后复发另一种类型的胶质瘤的患者中，使用替莫唑胺 1 周/1 周停药（ddTMZ）方案的疗效和耐受性。患者接受 ddTMZ 治疗，剂量为 100-150mg/m2/d（28 天周期的第 1-7 天和第 15-21 天）。所有患者 MRI 上均有增强病变，使用 RANO 标准评估 MRI 反应；完全和部分缓解被认为是客观缓解。53 例患者纳入研究。ddTMZ 周期的中位数为 4（范围 1-12）。8 例患者因毒性而停止化疗。24 例进展性胶质母细胞瘤患者中有 2 例出现客观缓解；胶质母细胞瘤 6 个月无进展生存率（PFS-6）为 29%。16 例复发性 WHO 2 或 3 级星形细胞瘤或少突胶质细胞瘤或少突星形细胞瘤患者中有 3 例出现客观缓解，这些患者的 PFS-6 为 38%。在 12 例可评估的复发性 WHO 2 或 3 级少突胶质细胞瘤或少突星形细胞瘤合并 1p 和 19q 缺失患者中，有 4 例出现客观缓解；这些患者的 PFS-6 为 62%。本研究表明，ddTMZ 在复发性胶质瘤中是安全有效的，尽管之前接受过替莫唑胺和/或亚硝脲化疗。我们的数据并未表明该方案比标准的 1 天-5 天每 4 周方案更有效。
