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HPB Surgery
Volume 7, Issue 3, Pages 219-224
http://dx.doi.org/10.1155/1994/54058

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

1Department of Surgery and Pathology, North Shore University Hospital, Manhasset 11030, NY, USA
2Surgical Oncology, St. Vincent's Hospital, 153 West 11th St., New York 10011, USA

Received 6 October 1992; Accepted 24 April 1993

Copyright © 1994 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Although continuous hepatic artery infusions (CHAI) of (FUDR) Floxuridine have been effective in reducing the size of colorectal hepatic metastases the toxicity of the infusions have been high with almost a quarter of the patients developing biliary sclerosis. Techniques to lower toxicity, yet continue the beneficial antitumor effects, are being investigated. One suggested strategy is to change the flow pattern of the continuous infusion from a constant rate to a day cycled pattern. In this infusion a continuous rate is given over a 24 hour period with 60% of the infusion delivered between 3 PM and 9 PM and the least amount of infusion delivered between 3 AM and 9 PM. Previous research has suggested that this day cycle pattern will lower the toxicity of the infusion. This experiment is a test of “day cycled” continuous hepatic artery infusions in rats bearing hepatic metastases from a colon adenocarcinoma. Previous research from our laboratory has shown a lowered toxicity when the constant infusion was replaced with the day cycled pattern.

In the present study 10 rats with hepatic adenocarcinoma metastases were placed on constant CHAI of FUDR at 10mg/kg/day for 14 days. There was an 80% mortality from chemotherapy toxicity and a 90% 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 previous group. This study demonstrated that “day cycled” CHAI of FUDR was substantially less toxic and that the antitumor effect was identical to the constant infusion.