Combination therapy of rat brain tumours using localized interstitial hyperthermia and intra-arterial chemotherapy

Several investigators have reported that a high concentration of drugs in a tumour can be achieved using intra-arterial (IA) chemotherapy. This treatment was highly effective, especially in brain tumours, but the actual therapeutic advantage is still unknown. There are also indications that human malignant gliomas can effectively be treated using interstitial hyperthermia. Therefore, a combined treatment of IA chemotherapy and interstitial hyperthermia should be very promising and this has been studied in a tumour model. Wistar rats with isotransplanted C(6) gliomas in the brain were treated with adriamycin (ADR, 1.0 mg/kg body weight) either infused via the carotid artery (i.a.) or via the tail vein (i.v.), with or without interstitial hyperthermia. Hyperthermia of the tumours was applied using a homemade radiofrequency antenna (RF-heating) and a heating device that maintained the tumour temperature above 40 degrees C. Concentration of adriamycin in tumours after treatment was measured using HPLC. The effectiveness of treatment was determined by the survival time of the animals and histopathological examinations. The highest uptake of adriamycin in the rat C(6) glioma was obtained when the animals were treated with hyperthermia and i.a. ADR infusion (p <0.01). These animals also showed significantly longer overall survival time (SF50 =46 days) in comparison to the other treatments (p < 0.05). The histological studies demonstrated a necroti c tumour; however, the surrounding normal brain tissue remained intact. Thus, a combination of IA chemotherapy with adriamycin and localized interstitial hyperthermia enhances considerably the efficacy of adriamycin and has a greater antitumour effect for malignant brain tumours. This method is suitable for clinical use, and may be a new strategy for treating gliomas not successfully treated today.