A nitrosourea derivative,
ACNU (
nimustine hydrochloride), is often used in the
chemotherapy of
brain tumors and shows considerable efficacy, since it crosses the blood-brain barrier (B.B.B.). This
drug is also considered to be useful for intrathecal treatment of meningeal gliomatosis (MG) because of its short half-life in the blood or cerebrospinal fluid (CSF) and its strong cytotoxicity for
glioma cells. In order to evaluate the efficacy of intrathecal
therapy of MG with
ACNU, MG models, which were produced by intracisternal inoculation of rat C6
glioma, were treated with intrathecal or
intravenous administration of
ACNU. When intrathecally administered 1 day or 3 days after
tumor inoculation,
ACNU (1 mg/kg) significantly prolonged the survival time of MG rats, where ILS was 35.7 to 42.9% and 24.1 to 25.0%, respectively. In MG rats which were treated intrathecally with
ACNU (1 mg/kg) 5 days after
tumor inoculation or intravenously with
ACNU (15 mg/kg),
ACNU failed to prolong survival time compared with the controls. It might therefore be suggested that intrathecal
chemotherapy with a low dose of
ACNU is effective in the early stages of MG, in which intravenous treatment with a high dose of
ACNU is ineffective.