Pre-clinical study of the epinephrine-cisplatin association for the treatment of intraperitoneal carcinomatosis

We have previously shown that intraperitoneal (i.p.) epinephrine enhances t umour penetration and anti-cancer activity of i.p.-administered cisplatin i n rats with peritoneal carcinomatosis. Here, we show a direct correlation b etween the i.p. epinephrine concentration and cisplatin accumulation in rat peritoneal tumour nodules up to a concentration of 5 mg/l. This concentrat ion leads to a maximal 3.7-fold increase of tumour platinum content and a m aximal vasoconstriction of the peritoneal and tumour superficial microcircu lation when registered by a laser doppler probe. Further, epinephrine half- life was 20.8 +/- 3.6 min in the peritoneal cavity of two laparotomized pig s. In these animals, epinephrine plasma concentration, heart rate and systo lic blood pressure were dependent on the intraperitoneal dose of epinephrin e, and life-threatening signs were not observed in either animal. In conclu sion, a 5 mg/l concentration of epinephrine could be safely maintained in p eritoneal fluid by regular replacement. This concentration is sufficient to maintain a constant vasoconstriction of the peritoneal and tumoral microva scular bed, and enhance the slow diffusion of cisplatin into peritoneal tum our nodules in the course of per-operative intraperitoneal chemotherapy. (C ) 2001 Harcourt Publishers Ltd.