Pre-irradiation internal carotid artery BCNU in treatment of glioblastoma multiforme.
High-dose 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) infusion into the internal carotid artery following cranial irradiation in the treatment of glioblastoma multiforme is accompanied by evidence of leukoencephalopathy in a significant number of patients. In an attempt to avoid this problem, a phase I trial was performed using intracarotid BCNU infusion before irradiation. Twenty-eight patients with grade III/III astrocytoma (World Health Organization Classification, equivalent to Kernohan grade IV) received a 400-mg infusion of BCNU into the infraophthalmic carotid artery. The treatment was repeated every 4 weeks for a total of four cycles prior to cranial irradiation (5500 to 6000 cGy). The major toxic sequelae included nausea and vomiting (24%), decreased visual acuity (14%), transient cerebral ischemia (3.5%), and thrombocytopenia (3.5%). Fatal leukoencephalopathy occurred in two patients. The median survival time was 37 weeks for all evaluable patients and 56+ weeks for those completing the protocol. The tumor response to drug infusion as judged by computerized tomography (CT) was complete in 22% of patients and partial in 22%; 56% showed no CT tumor response. Pre-irradiation intracarotid artery BCNU benefits a very small group of patients with grade III/III astrocytoma. The associated severe leukoencephalopathy makes this mode of therapy unacceptable for a phase III trial.
Bashir
R
R
Brain Tumor Center, Massachusetts General Hospital, Boston.
Hochberg
F H
FH
Linggood
R M
RM
Hottleman
K
K
D000328:Adult; D001927:Brain Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D002330:Carmustine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002343:Carotid Artery, Internal; D003131:Combined Modality Therapy; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D007261:Infusions, Intra-Arterial; D008875:Middle Aged; D010865:Pilot Projects; D013921:Thrombocytopenia / Q000139:chemically induced; D014057:Tomography, X-Ray Computed
D002330:Carmustine