Intrathecal chemotherapy with ACNU in a meningeal gliomatosis rat model

Intrathecal administration of ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitroso urea hydrochloride) had a remarkable chemotherapeutic effect in a rat model of meningeal gliomatosis. This effect was evaluated in rats with meningeal gliomatosis induced by an intracisternal inoculation of rat C6 glioma cells. The median survival time of the rats treated with a single dose of intrathecal ACNU (1 mg/kg) on Day 1 or Day 3 after tumor inoculation was significantly prolonged by 35.7% to 42.9% or 25.0% to 28.6%, respectively, as compared with that of the control animals. Meningeal gliomatosis rat models treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or intravenously with ACNU (15 mg/kg) both failed to prolong the survival time of the animals. These findings suggest that intrathecal chemotherapy with a low dose of ACNU is effective in the early stages of meningeal gliomatosis, whereas intravenous chemotherapy with a high dose of ACNU is always ineffective.