The effect of amphotericin B on the survival of brain-tumor-bearing mice treated with CCNU.

Abstract

The membrane-active polyene, amphotericin B (AMB) has been shown to enhance or potentiate the effects of various chemotherapeutic agents against tumor cells in tissue culture. Because of the need to increase the efficacy of the nitrosoureas in brain-tumor chemotherapy, we have studied the effect of the nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), with or without AMB pretreatment. The intraperitoneal administration of 25 mg/kg of AMB 24 hours before 5, 10, 20 or 30 mg/kg of intraperitoneal CCNU did not result in a significant improvement in survival. The failure of intraperitoneal AMB to potentiate the effect of CCNU was likely a failure in drug delivery, since AMB crosses the blood-brain barrier very poorly. To circumvent the drug-delivery problem, AMB was administered intracerebrally directly into the tumor-bearing hemisphere. With 0.5 mg/kg of intracerebral AMB administered 24 hours before 10 mg/kg CCNU was given intraperitoneally, the life-span was significantly increased over the control group. The same dose of CCNU alone did not significantly increase survival. When 0.2, 0.5, or 1.0 mg/kg AMB was administered intracerebrally 24 hours before 20 mg/kg of interaperitoneal CCNU, survival was significantly increased over those groups receiving the same dose of CCNU alone. It is concluded that direct intracerebral administration of AMB enhances or potentiates the therapeutic effect of CCNU in this brain-tumor model.