5月10日，The Lancet Oncology發(fā)表的一項(xiàng)研究表明,，在老年惡性星形細(xì)胞瘤患者的治療中,，替莫唑胺單藥不劣于單純放療；O6-甲基鳥(niǎo)嘌呤-DNA甲基轉(zhuǎn)移酶（MGMT）啟動(dòng)子甲基化似乎是一種可預(yù)測(cè)治療轉(zhuǎn)歸的生物標(biāo)志物,，有助于治療決策,。
該研究從2005年5月15日至2009年11月2日納入了年齡＞65歲且卡諾夫斯基體能狀態(tài)評(píng)分（KPS）≥60分的間變性星形細(xì)胞瘤或膠質(zhì)母細(xì)胞瘤患者。
患者被隨機(jī)分配到替莫唑胺（100mg/m2,，第1～7日給藥,，用藥1周，停藥1周）或放療（60.0Gy,，30次分割,，每次1.8～2.0Gy，6～7周照射完畢）組,。
主要終點(diǎn)是總生存期（OS）,，非劣效性界值為25%。
結(jié)果顯示,，在584例被篩查的患者中,，共有412例入組。373例患者（替莫唑胺組195例,，放療組178例）符合研究條件者被分析療效,。
替莫唑胺和放療組中位OS分別為8.6和9.6個(gè)月[危險(xiǎn)比（HR）=1.09,，P=0.033],，中位無(wú)事件生存期（EFS）無(wú)顯著差異（3.3個(gè)月 對(duì) 4.7個(gè)月,，HR=1.15，P=0.043）,。
209例被檢查的患者中有73例（35%）被發(fā)現(xiàn)存在腫瘤MGMT啟動(dòng)子甲基化,。
MGMT啟動(dòng)子甲基化較未甲基化與較長(zhǎng)的OS有關(guān)（11.9個(gè)月 對(duì) 8.2個(gè)月，HR=0.62,，P=0.014）,。
在MGMT啟動(dòng)子甲基化的患者中，接受替莫唑胺治療者EFS長(zhǎng)于接受放療者（8.4個(gè)月 對(duì)4.6個(gè)月）,；相反,，在MGMT啟動(dòng)子未甲基化的患者中，接受替莫唑胺治療者EFS短于接受放療者（3.3個(gè)月 對(duì)4.6個(gè)月）,。
最常見(jiàn)的3～4級(jí)治療相關(guān)不良事件為中性粒細(xì)胞減少（替莫唑胺組16例 對(duì)放療組2例）,、淋巴細(xì)胞減少（46例 對(duì) 1例）、血小板減少（14例 對(duì) 4例）,、肝酶濃度升高（30例 對(duì) 16例）,、感染（35例 對(duì) 23例）和血栓栓塞事件（24例 對(duì) 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.
