A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain
A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain
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DOI：
10.1016/0360-3016(95)02025-x
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发表时间：
1996-03-01
影响因子：
7
通讯作者：
Friedman, A
中科院分区：
文献类型：
--
作者：
Halperin, EC;Herndon, J;Friedman, A
目的：本研究旨在探讨克服脑间变性胶质瘤外照射(ERT)加卡莫司汀(BCNU)耐药的策略。患者年龄大于或等于15岁，有恶性胶质瘤的组织学诊断，卡氏行为状态(KPS)大于或等于60%。方法与材料：在随机试验1中，患者在ERT治疗的第一周和第四周被分配到接受ERT(61.2GY)或ERT加丝裂霉素C(MITO，IV 125 mg/m(2))。在这种治疗之后，患者继续接受随机2，在那里他们被分配接受BCNU(静脉注射)。每隔6周给予200 mg/m(2)或6-巯基嘌呤(6-MP，750 mg/m(2)静脉滴注，每日3天，每6周1次)，BCNU于6-MP治疗的第3天给药。327例患者接受了随机化治疗。164例接受了单纯ERT，163例接受了ERT+MITO[平均年龄52.7岁；男性63%；多形性胶质母细胞瘤69%；手术切除66%；KPS>90%]。随机化1或2的生存逐步分析表明：(A)年龄大于或等于45岁(B)KPS和Lt；90%；(C)GBM/胶质肉瘤组织学；(D)立体定向活检，而不是开放活检或切除。随机1组(ERT+MITO)的中位生存期为10.8个月。随机化2的中位生存期BCNU/6MP组为9.3个月，而BCNU组为11.4个月(p=0.35)。卡莫司汀/6-MP对GBM/GS以外的组织学显示了可能的生存益处。ERT组中在随机化2之前终止研究的患者比例显著低于ERT+MITO组(20vs.37%，p&0.001)。结论：(A)ERT加MITO对生存率没有影响；(B)ERT+MITO治疗的患者在随机化2之前终止治疗的风险更大；(C)在BCNU的基础上加入6-MP并没有显著的生存益处。
Purpose: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were greater than or equal to 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) greater than or equal to 60%.Methods and Materials: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C(Mito, IV 125 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6-MP, 750 mg/m(2) IV daily for 3 days every 6 weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average age 52.7 Sears; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS greater than or equal to 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age greater than or equal to 45 years (b) KPS < 90%; (C) GBM/Gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001).Conclusions: (a) The addition of Mito to ERT had no impart on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.