title: A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma.
abstract: 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.
authors.affiliation: Division of Neurology, St. Joseph's Hospital, Phoenix, Arizona.
authors.forename: W R
authors.initials: WR
authors.lastname: Shapiro
authors.forename: S B
authors.initials: SB
authors.lastname: Green
authors.forename: P C
authors.initials: PC
authors.lastname: Burger
authors.forename: R G
authors.initials: RG
authors.lastname: Selker
authors.forename: J C
authors.initials: JC
authors.lastname: VanGilder
authors.forename: J T
authors.initials: JT
authors.lastname: Robertson
authors.forename: J
authors.initials: J
authors.lastname: Mealey
authors.forename: J
authors.initials: J
authors.lastname: Ransohff
authors.forename: M S
authors.initials: MS
authors.lastname: Mahaley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002330:Carmustine / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005910:Glioma / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D015173:Supratentorial Neoplasms / Q000188:drug therapy* / Q000628:therapy; D016019:Survival Analysis
chemical_list: D005472:Fluorouracil; D002330:Carmustine