Leptomeningeal dissemination is one of the major causes which increase the morbidity and mortality of the patients with malignant
brain tumors. The incidence of this complication is increasing, however, no sufficient treatment is available at present. Therefore, in an attempt to establish a new treatment, we studied toxicity and
therapeutic effect of intrathecal
ACNU (
nimustine hydrochloride) using experimental animals. Systemic and local toxicity was tested in normal rats that received
ACNU intracisternally. The animals given
ACNU more than 3.0 mg/kg progressively lost their
body weight, and
ACNU 6.0 mg/kg was fatal in 80% of animals. Animals given
ACNU less than 1.5 mg/kg gained weight in the same rate as in control animals. Increased capillary permeability to intravenous
Evans blue was observed in the subpial region of the brain in the rats given
ACNU 6.0 mg/kg intracisternally. The increase of capillary permeability was dominant along the ambient cistern, hypocampal fissure, and at the base of the brain. Demyelinization and loss of neurons were seen in the same areas as well. These changes were not observed in the animal given
ACNU less than 1.5 mg/kg.
Therapeutic effect of intrathecal
ACNU against the leptomeningeal
tumor was studied in rats with
meningeal carcinomatosis which was induced by intracisternal inoculation of 1 X 10(4) cells of Walker 256
carcinosarcoma. The median survival times of the animal given
ACNU 1.5 mg/kg intrathecally on day 2 or 5 after
tumor inoculation were prolonged by 55 to 64%, and 64 to 145%, respectively, as compared to those of untreated control animals (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)