Radiation Oncology Department, Marmara University Hospital, Tophanelioglu Cad. 13/15 Altunizade, 34660 Istanbul, Turkey.
J Neurooncol. 2011 Jul;103(3):585-93. doi: 10.1007/s11060-010-0423-2. Epub 2010 Sep 29.
The current standard therapy for newly diagnosed glioblastoma is multimodal, comprising surgical resection plus radiotherapy and concurrent temozolomide, then adjuvant temozolomide for 6 months. This has been shown to provide survival benefits; however, the prognosis for these patients remains poor, and most relapse. The objective of this prospective Phase II study was to evaluate the efficacy and tolerability of protracted, dose-dense temozolomide therapy (100 mg/m(2) for 21 consecutive days of a 28-day cycle) in patients with recurrent glioblastoma or grade 3 gliomas who had previously received standard therapy. Of the 25 patients included (median age 50 years), 20 were evaluable for radiologic response. Two patients had partial responses and 10 had stable disease (60% overall clinical benefit); 8 patients (40%) progressed after the first treatment cycle. Five patients were not assessed for radiologic response due to early clinical progression but were included in the progression-free survival (PFS) and overall survival (OS) analyses. The median follow-up time was 7 months (range, 1-14 months). The median PFS was 3 months (95% confidence interval, CI, 1.8-4.2) and the median OS was 7 months (95% CI 5.1-8.9). The 6-month PFS rate (primary endpoint) was 17.3% (95% CI 1.7-32.2) and the 1-year OS rate was 12% (95% CI -1-25). This regimen was well tolerated. The most frequent adverse event was lymphopenia (grade 3-4 in 20 patients); no opportunistic infections were reported. Treatment was discontinued due to toxicity in 2 patients (grade 4 hepatic toxicity and thrombocytopenia). These data suggest that protracted, dose-dense temozolomide had modest activity with manageable toxicity in patients with recurrent high-grade glioma previously treated with temozolomide.
目前新诊断的胶质母细胞瘤的标准治疗是多模式的，包括手术切除加放疗和同期替莫唑胺，然后辅助替莫唑胺治疗 6 个月。这已被证明能提供生存获益；然而，这些患者的预后仍然很差，大多数患者复发。本前瞻性 II 期研究的目的是评估在先前接受标准治疗的复发性胶质母细胞瘤或 3 级胶质瘤患者中，延长、剂量密集型替莫唑胺治疗（28 天周期内连续 21 天给予 100mg/m2）的疗效和耐受性。在纳入的 25 例患者中（中位年龄 50 岁），20 例可评估影像学反应。2 例患者有部分缓解，10 例患者疾病稳定（总临床获益率为 60%）；8 例患者（40%）在第一个治疗周期后进展。由于早期临床进展，5 例患者未评估影像学反应，但包括在无进展生存期（PFS）和总生存期（OS）分析中。中位随访时间为 7 个月（范围，1-14 个月）。中位 PFS 为 3 个月（95%置信区间，CI，1.8-4.2），中位 OS 为 7 个月（95%CI，5.1-8.9）。6 个月 PFS 率（主要终点）为 17.3%（95%CI，1.7-32.2），1 年 OS 率为 12%（95%CI，-1-25）。该方案耐受性良好。最常见的不良事件是淋巴细胞减少症（20 例患者中有 3-4 级）；未报告机会性感染。由于毒性，有 2 例患者停止治疗（4 级肝毒性和血小板减少症）。这些数据表明，在先前接受替莫唑胺治疗的复发性高级别胶质瘤患者中，延长、剂量密集型替莫唑胺具有适度的活性，且毒性可管理。
