A RANDOMIZED COMPARISON OF INTRAARTERIAL VERSUS INTRAVENOUS BCNU, WITH OR WITHOUT INTRAVENOUS 5-FLUOROURACIL, FOR NEWLY DIAGNOSED PATIENTS WITH MALIGNANT GLIOMA
A RANDOMIZED COMPARISON OF INTRAARTERIAL VERSUS INTRAVENOUS BCNU, WITH OR WITHOUT INTRAVENOUS 5-FLUOROURACIL, FOR NEWLY DIAGNOSED PATIENTS WITH MALIGNANT GLIOMA
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DOI：
10.3171/jns.1992.76.5.0772
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发表时间：
1992-05-01
影响因子：
4.1
通讯作者：
MAHALEY, MS
中科院分区：
文献类型：
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作者：
SHAPIRO, WR;GREEN, SB;MAHALEY, MS
这项III期试验测试了动脉内注射1，3-双（2-氯乙基）-1-亚硝基脲（BCNU）治疗新切除的恶性胶质瘤的有效性和安全性，比较了动脉内注射BCNU和静脉内注射BCNU（200 mg/m2，每8周一次），每种方案均不使用或使用静脉内5-氟尿嘧啶（BCNU后2周给予1 gm/m2，每日3次）。所有患者还接受了放射治疗。共有505名患者在研究中被随机分配。排除了57例患者，主要是因为神经病理学错误，其余448例患者构成有效研究组。在505例患者中，190例患者不能接受动脉内BCNU，315例患者被随机分配接受动脉内（167例患者）和静脉内（148例患者）BCNU。精算分析（对数秩）表明动脉内组的生存率降低（p = 0.03）。在动脉内组中观察到严重毒性; 16例患者（9.5%）出现不可逆性脑病，伴脑水肿的计算机断层扫描证据，26例患者（15.5%）出现输注颈动脉同侧视力丧失。5-氟尿嘧啶的给药不影响生存率。多形性胶质母细胞瘤患者静脉和动脉内BCNU治疗的生存率没有差异，但动脉内BCNU治疗的间变性星形细胞瘤患者的生存率低于静脉内BCNU治疗的患者（p = 0.002）。神经病理学上，动脉内BCNU产生白色坏死。结论是动脉内BCNU是既不安全，也不有效，在延长生存期时，本研究中使用的方法，新诊断的恶性胶质瘤患者管理。
This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)- 1 -nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.