Stupp Roger, Dietrich Pierre-Yves, Ostermann Kraljevic Sandrine, Pica Alessia, Maillard Ivan, Maeder Phillipe, Meuli Reto, Janzer Robert, Pizzolato Gianpaolo, Miralbell Raymond, Porchet François, Regli Luca, de Tribolet Nicolas, Mirimanoff René O, Leyvraz Serge
Department of Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
J Clin Oncol. 2002 Mar 1;20(5):1375-82. doi: 10.1200/JCO.2002.20.5.1375.
Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM.
Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m(2)/d x 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy x 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m(2)/d x 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival.
Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome.
Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.
替莫唑胺是一种新型口服烷化剂，已证实对复发性间变性星形细胞瘤和多形性胶质母细胞瘤（GBM）患者作为二线治疗有效。进行这项II期研究以确定同步放疗加替莫唑胺治疗后辅助替莫唑胺治疗对新诊断GBM患者的安全性、耐受性和疗效。
64例患者入组这项开放标签的II期试验。替莫唑胺（75mg/m²/d×7天/周，共6周）口服，与分割放疗（总剂量60Gy：2Gy×5天/周，共6周）同步进行，随后进行替莫唑胺单药治疗（200mg/m²/d×5天，每28天为一个周期，共六个周期）。主要终点是安全性和耐受性，次要终点是总生存期。
同步放疗加替莫唑胺治疗安全且耐受性良好。非血液学毒性罕见，严重程度为轻至中度。在同步治疗阶段，6%的患者出现3级或4级中性粒细胞减少、血小板减少或两者兼有，包括两例卡氏肺孢子虫严重感染。在辅助替莫唑胺治疗期间，分别有2%和6%的周期与3级和4级中性粒细胞减少或血小板减少相关。中位生存期为16个月，1年和2年生存率分别为58%和31%。年龄小于50岁的患者和接受肿瘤切除手术患者的生存结果最佳。
持续每日使用替莫唑胺并同步放疗是安全的。这种同步放化疗后辅助化疗的方案可能延长胶质母细胞瘤患者的生存期。有必要进一步研究，一项随机试验正在进行中。
