Food and Drug Administration drug approval summary: Temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme
Food and Drug Administration drug approval summary: Temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme
复制标题
DOI：
10.1158/1078-0432.ccr-05-0722
复制
发表时间：
2005-10-01
影响因子：
11.5
通讯作者：
Pazdur, R
中科院分区：
文献类型：
--
作者：
Cohen, MH;Johnson, JR;Pazdur, R
2005年3月15日，美国食品药品监督管理局批准替莫唑胺（Temodar胶囊，先灵葆雅研究所）用于治疗新诊断的多形性胶质母细胞瘤成人患者，同时进行放疗，然后作为维持治疗。573例多形性胶质母细胞瘤患者被随机分配至单纯放疗组（n = 287）或单纯放疗组（n = 286）。在替莫唑胺+放疗组中，接受替莫唑胺+放疗（n mg/m2）的患者在放疗期间（42-49天）接受替莫唑胺（75 mg/m2），每日一次。4周后，每4周给予替莫唑胺6 mg/m2，每天150或200 mg，共5天。对照组患者仅接受放疗。在两组中，放射治疗以60戈伊/30次的剂量递送至肿瘤部位，边缘为2至3 cm。在替莫唑胺+放疗治疗期间需要预防卡氏肺孢子虫肺炎，并持续至淋巴细胞减少症恢复（通用毒性标准等级< 1）。在疾病进展时，单独放疗组282例患者中有161例（57%）接受了替莫唑胺挽救治疗，而替莫唑胺+放疗组277例患者中有62例（22%）接受了替莫唑胺+放疗合并治疗和维持治疗患者的总生存率显著提高，风险比为0.63（95%置信区间，0.52-0.75;对数秩，P < 0.0001）。中位生存期为14.6个月（替莫唑胺+放疗）与12.1个月（单纯放疗）。替莫唑胺治疗期间的不良事件包括血小板减少、恶心、呕吐、厌食、便秘、脱发、头痛、疲劳和惊厥。
On March 15, 2005, the U.S. Food and Drug Administration approved temozolomide (Temodar capsules, Schering-Plough Research Institute) for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment. Five hundred seventy-three glioblastoma multiforme patients were randomized to = 287) or radiotherapy alone (n = 286). Patients receive either temozolomicle + radiotherapy (n mg/m(2)) in the temozolomide + radiotherapy arm received concomitant temozolomide (75 once daily for the duration of radiation therapy (42-49 days). This was followed, 4 weeks later, by six mg/m(2) cycles-of temozolomicle, 150 or 200 daily for 5 days, every 4 weeks. Patients in the control arm received radiotherapy only. In both arms, radiotherapy was delivered as 60 Gy/30 fractions to the tumor site with a 2 to 3 cm margin. Pneumocystis carinii pneumonia prophylaxis was required during temozolomide + radiotherapy treatment and was continued until recovery of lymphocytopenia (Common Toxicity Criteria grade < 1). At disease progression, temozolomide salvage treatment was given to 161 of 282 patients (57%) in the radiotherapy alone arm, and to 62 of 277 patients (22%) in the temozolomide + radiotherapy arm. Patients receiving concomitant and maintenance temozolomide + radiotherapy had significantly improved overall survival, The hazard ratio was 0.63 (95% confidence interval, 0.52-0.75; log-rank, P < 0.0001). Median survival was 14.6 months (temozolomicle + radiotherapy) versus 12.1 months (radiotherapy alone). Adverse events during temozolomide treatment included thrombocytopepia, nausea, vomiting, anorexia, constipation, alopecia, headache, fatigue, and convulsions.