Enhancement of ACNU treatment of the BT4An rat glioma by local brain hyperthermia and intra-arterial drug administration.

To evaluate the role of intra-arterial (i.a.) chemotherapy, intravenous (i.v.) chemotherapy, and local brain hyperthermia in the treatment of gliomas, the effect of i.v. versus i.a. drug delivery, with or without local brain hyperthermia, was evaluated in BD IX rats with BT4An gliomas implanted in the right frontal lobe. The rats were given ACNU 18 mg/kg i.a. in the right carotid artery or i.v. in the inferior cava with or without local microwave hyperthermia at 42.4 degrees C for 45 min. ACNU i.v. alone had no notable effect on survival. Survival was prolonged when ACNU without hyperthermia was given i.a. instead of i.v. (P < 0.05). Thermochemotherapy with ACNU i.a. was more effective than with ACNU i.v. (P < 0.01). Survival improved as hyperthermia enhanced the i.v. drug effect (P < 0.01), and hyperthermia also improved the i.a. ACNU effect (P < 0.01). Post-treatment survival was more than doubled for the group given combined i.a. ACNU and hyperthermia, compared to controls. Thermochemotherapy, particularly with i.a. drug administration, seems to be a promising new approach for the treatment of primary brain tumours. However, more knowledge about tolerance of human brain tissue to hyperthermia is necessary before this treatment modality is used in patients with a reasonable life expectancy.