5月10日，The Lancet Oncology发表的一项研究表明，在老年恶性星形细胞瘤患者的治疗中，替莫唑胺单药不劣于单纯放疗；O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化似乎是一种可预测治疗转归的生物标志物，有助于治疗决策。
该研究从2005年5月15日至2009年11月2日纳入了年龄＞65岁且卡诺夫斯基体能状态评分（KPS）≥60分的间变性星形细胞瘤或胶质母细胞瘤患者。
患者被随机分配到替莫唑胺（100mg/m2，第1～7日给药，用药1周，停药1周）或放疗（60.0Gy，30次分割，每次1.8～2.0Gy，6～7周照射完毕）组。
主要终点是总生存期（OS），非劣效性界值为25%。
结果显示，在584例被筛查的患者中，共有412例入组。373例患者（替莫唑胺组195例，放疗组178例）符合研究条件者被分析疗效。
替莫唑胺和放疗组中位OS分别为8.6和9.6个月[危险比（HR）=1.09，P=0.033]，中位无事件生存期（EFS）无显著差异（3.3个月 对 4.7个月，HR=1.15，P=0.043）。
209例被检查的患者中有73例（35%）被发现存在肿瘤MGMT启动子甲基化。
MGMT启动子甲基化较未甲基化与较长的OS有关（11.9个月 对 8.2个月，HR=0.62，P=0.014）。
在MGMT启动子甲基化的患者中，接受替莫唑胺治疗者EFS长于接受放疗者（8.4个月 对4.6个月）；相反，在MGMT启动子未甲基化的患者中，接受替莫唑胺治疗者EFS短于接受放疗者（3.3个月 对4.6个月）。
最常见的3～4级治疗相关不良事件为中性粒细胞减少（替莫唑胺组16例 对放疗组2例）、淋巴细胞减少（46例 对 1例）、血小板减少（14例 对 4例）、肝酶浓度升高（30例 对 16例）、感染（35例 对 23例）和血栓栓塞事件（24例 对 8例）。（生物谷Bioon.com）
doi:10.1016/S1470-2045(12)70164-X
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Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial
Original TextProf Wolfgang Wick MD a c e , Prof Michael Platten MD a c e, Christoph Meisner PhD d, J?rg Felsberg MD k, Ghazaleh Tabatabai MD e o, Matthias Simon MD f, Prof Guido Nikkhah MD g, Kirsten Papsdorf MD h, Prof Joachim P Steinbach MD e j, Michael Sabel MD k, Stephanie E Combs MD b, Jan Vesper MD g k, Christian Braun MD e, Prof Jürgen Meixensberger MD i, Ralf Ketter MD m, Regine Mayer-Steinacker MD n, Prof Guido Reifenberger MD l, Prof Michael Weller MD e o, for the NOA-08 Study Group of the Neuro-oncology Working Group (NOA) of the German Cancer Society?
Background
Radiotherapy is the standard care in elderly patients with malignant astrocytoma and the role of primary chemotherapy is poorly defined. We did a randomised trial to compare the efficacy and safety of dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma.
Methods
Between May 15, 2005, and Nov 2, 2009, we enrolled patients with confirmed anaplastic astrocytoma or glioblastoma, age older than 65 years, and a Karnofsky performance score of 60 or higher. Patients were randomly assigned 100 mg/m2 temozolomide, given on days 1—7 of 1 week on, 1 week off cycles, or radiotherapy of 60·0 Gy, administered over 6—7 weeks in 30 fractions of 1·8—2·0 Gy. The primary endpoint was overall survival. We assessed non-inferiority with a 25% margin, analysed for all patients who received at least one dose of assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01502241.
Findings
Of 584 patients screened, we enrolled 412. 373 patients (195 randomly allocated to the temozolomide group and 178 to the radiotherapy group) received at least one dose of treatment and were included in efficacy analyses. Median overall survival was 8·6 months (95% CI 7·3—10·2) in the temozolomide group versus 9·6 months (8·2—10·8) in the radiotherapy group (hazard ratio [HR] 1·09, 95% CI 0·84—1·42, pnon-inferiority=0·033). Median event-free survival (EFS) did not differ significantly between the temozolomide and radiotherapy groups (3·3 months [95% CI 3·2—4·1] vs 4·7 [4·2—5·2]; HR 1·15, 95% CI 0·92—1·43, pnon-inferiority=0·043). Tumour MGMT promoter methylation was seen in 73 (35%) of 209 patients tested. MGMT promoter methylation was associated with longer overall survival than was unmethylated status (11·9 months [95% CI 9·0 to not reached] vs 8·2 months [7·0—10·0]; HR 0·62, 95% CI 0·42—0·91, p=0·014). EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy (8·4 months [95e% CI 5·5—11·7] vs 4·6 [4·2—5·0]), whereas the opposite was true for patients with no methylation of the MGMT promoter (3·3 months [3·0—3·5] vs 4·6 months [3·7—6·3]). The most frequent grade 3—4 intervention-related adverse events were neutropenia (16 patients in the temozolomide group vs two in the radiotherapy group), lymphocytopenia (46 vs one), thrombocytopenia (14 vs four), raised liver-enzyme concentrations (30 vs 16), infections (35 vs 23), and thromboembolic events (24 vs eight).
Interpretation
Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making.
Funding
Merck Sharp & Dohme.
