A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma

• Published in: Journal of neurosurgery Vol. 76; no. 5; pp. 772 - 781
• Main Authors: SHAPIRO, W. R, GREEN, S. B, BURGER, P. C, SELKER, R. G, VANGILDER, J. C, ROBERTSON, J. T, MEALEY, J. JR, RANSOHOFF, J, MAHALEY, M. S
• Format: Journal Article
• Language: English
• Published: Park Ridge, IL American Association of Neurological Surgeons 01-05-1992
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carmustine - administration & dosage; Carmustine - adverse effects; Chemotherapy; Combined Modality Therapy; Female; Fluorouracil - administration & dosage; Glioma - drug therapy; Glioma - therapy; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Proportional Hazards Models; Supratentorial Neoplasms - drug therapy; Supratentorial Neoplasms - therapy; Survival Analysis; Antineoplastic agent; Human; Malignant glioma; Intracranial; Nervous system diseases; Alkylating agent; Treatment; Intravenous administration; Intraarterial administration; Malignant tumor; Comparative study
• ISSN: 0022-3085; 1933-0693
• DOI: 10.3171/jns.1992.76.5.0772

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.