Systemic lidocaine enhancement of hyperthermia-induced tumor regression in transplantable murine tumor models

Abstract

Previously, we reported that local lidocaine infusion of a CA 755 mammary adenocarcinoma growing in C57BL X DBA/2 F1 mice, when combined with local heating for 1 hr in a 43.5 degrees water bath, significantly increased survival and inhibited tumor growth more than heating alone. Because of its clinical implications, systemic lidocaine was tested in the above model system and in a murine fibrosarcoma tumor model. An equivalent supraadditive, tumor-inhibitory effect of heat and lidocaine was obtained with both systemically and intratumor-administered lidocaine. The serum levels of lidocaine necessary to achieve tumor regression were within the therapeutic range for the control of arrhythmia in humans. Several treatment schedules, varying the mode of drug delivery, were evaluated. The effects of treatment on tumor growth characteristics were analyzed using an extension of the Cox survival model.