Kocher Martin, Frommolt Peter, Borberg Sigrid Klara, Rühl Ursula, Steingräber Maria, Niewald Markus, Staar Susanne, Stuschke Martin, Becker Gerd, Fischedick Arnt-René, Herfarth Klaus, Grauthoff Hermann, Müller Rolf-Peter
Department of Radiotherapy, University Hospital, Cologne, Germany.
Strahlenther Onkol. 2008 Nov;184(11):572-9. doi: 10.1007/s00066-008-1897-0. Epub 2008 Nov 19.
To evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients.
From February 2002 to July 2004, n = 65 patients from 11 German centers with macroscopic complete tumor resection were randomized to receive either postoperative radiotherapy alone (RT, n = 35) or postoperative radiotherapy with simultaneous temozolomide (RT + TMZ, n = 30). Patients were stratified according to age (< or =/>50 years) and WHO performance score (0-1 vs. 2). RT consisted of 60 Gy in 30 fractions. In the RT + TMZ arm, oral TMZ was administered daily at a dose of 75 mg/m(2) including weekends (40-42 doses). Adjuvant treatment was not given, but in both arms, patients with recurrent tumors and in good condition (WHO 0-2) were scheduled for salvage chemotherapy with TMZ.
The trial was stopped early due to the results of EORTC-study 26981-22981 that showed a survival benefit for the combination of concomitant and adjuvant TMZ compared to radiotherapy alone. In total, 62/65 patients were evaluable. Stratification variables were well balanced (< or = 50 years 26% vs. 20%, WHO 0-1 91% vs. 100%). Neither overall survival (median 17 vs. 15 months) nor progression-free survival (median 7 vs. 6 months) differed significantly between the two arms. In the RT (RT + TMZ) arm, 76% (62%) of the progressing patients received salvage chemotherapy with TMZ, 36% (50%) had a second resection. There was a time-constant trend for increased general quality of life (EORTC questionnaire QLQ C30) and brain-specific quality of life (EORTC questionnaire B20) in the combined arm. Lymphopenia G3-4 was more frequent (33 vs. 6%) in the RT + TMZ arm.
After early closure of this trial, a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated. In both arms, salvage therapies were frequently used and probably had a major effect on overall survival.
评估胶质母细胞瘤患者术后同步替莫唑胺放化疗的疗效。
2002年2月至2004年7月，来自德国11个中心的65例经宏观完全肿瘤切除的患者被随机分为两组，一组接受单纯术后放疗（RT，n = 35），另一组接受术后放疗并同步使用替莫唑胺（RT + TMZ，n = 30）。患者根据年龄（≤50岁与＞50岁）和世界卫生组织（WHO）体能状态评分（0 - 1分与2分）进行分层。放疗总剂量为60 Gy，分30次进行。在RT + TMZ组，口服替莫唑胺，剂量为75 mg/m²，每日一次，包括周末（共40 - 42剂）。未给予辅助治疗，但在两组中，复发且身体状况良好（WHO 0 - 2级）的患者计划接受替莫唑胺挽救化疗。
由于欧洲癌症研究与治疗组织（EORTC）26981 - 22981研究结果显示，与单纯放疗相比，同步及辅助使用替莫唑胺可提高生存率，该试验提前终止。总共62/65例患者可进行评估。分层变量分布均衡（≤50岁组分别为26%与20%，WHO 0 - （此处原文可能有误，推测应为0 - 1）分与2分组分别为91%与100%）。两组间总生存期（中位生存期分别为17个月与15个月）和无进展生存期（中位生存期分别为7个月与6个月）均无显著差异。在RT（RT + TMZ）组中，76%（62%）病情进展的患者接受了替莫唑胺挽救化疗，36%（50%）进行了二次手术。联合治疗组患者的总体生活质量（EORTC问卷QLQ C30）和脑部特定生活质量（EORTC问卷B20）呈持续上升趋势。RT + TMZ组3 - 4级淋巴细胞减少更为常见（分别为33%与6%）。
该试验提前结束后，未证实单纯同步替莫唑胺放化疗对无进展生存期有获益。两组均频繁使用挽救治疗，这可能对总生存期有重大影响。
