The Effects on Liver Metastases of Circadian Patterned Continuous Hepatic Artery Infusion of FUDR

摘要

Although continuous hepatic artery infusions (CHAI) of (FUDR) Floxuridine have been effective inreducing the size of colorectal hepatic metastases the toxicity of the infusions have been high with almosta quarter of the patients developing biliary sclerosis. Techniques to lower toxicity, yet continue thebeneficial antitumor effects, are being investigated. One suggested strategy is to change the flow patternof the continuous infusion from a constant rate to a day cycled pattern. In this infusion a continuous rateis given over a 24 hour period with 60% of the infusion delivered between 3 PM and 9 PM and the leastamount of infusion delivered between 3 AM and 9 PM. Previous research has suggested that this daycycle pattern will lower the toxicity of the infusion. This experiment is a test of “day cycled” continuoushepatic artery infusions in rats bearing hepatic metastases from a colon adenocarcinoma. Previousresearch from our laboratory has shown a lowered toxicity when the constant infusion was replaced withthe day cycled pattern.In the present study 10 rats with hepatic adenocarcinoma metastases were placed on constant CHAIof FUDR at 10mg/kg/day for 14 days. There was an 80% mortality from chemotherapy toxicity and a90% objective response rate. Nine other rats were treated with “day cycled” CHAI of FUDR at 15mg/kg/d. There was no mortality in this group and the objective response rate was 90% as in the previousgroup. This study demonstrated that “day cycled” CHAI of FUDR was substantially less toxic and thatthe antitumor effect was identical to the constant infusion.