Pharmacology of perioperative 5-fluorouracil

Abstract

Background: The purpose of this study was to analyze our current pharmacologic data regarding the perioperative use of 5-fluorouracil in the treatment of peritoneal surface malignancies. Methods Twenty-nine patients with peritoneal carcinomatosis from appendiceal malignancy were included in this pharmacological study. Results In the nine patients who received early postoperative intraperitoneal chemotherapy, the area under the curve for intraperitoneal 5-fluorouracil was 43,000 (±20,300)μg/ml × min and for intravenous 5-fluorouracil was 157 (±99)μg/ml × min. The area under the curve ratio was 422 (±360). In 20 patients who received intravenous 5-fluorouracil in the operating room intraperitoneal 5-fluorouracil levels maintained a higher level as compared to the intravenous drug level over the 90 min of drug sampling. The area under the curve ratio of peritoneal fluid to plasma was 2.3 (±1.3). The area under curve ratio of peritoneal fluid to tumor nodules was 9.9 (±9.8). The area under the curve ratio of plasma to tumor nodules was 5.2 (±4.7). Conclusions By modulating the route or timing of administration of 5-fluorouracil, it becomes a pharmacologic advantageous molecule in patients with peritoneal carcinomatosis of an appendiceal malignancy. 5-fluorouracil remains the cornerstone of the perioperative management of peritoneal carcinomatosis of gastrointestinal origin. © 2010 Wiley-Liss, Inc.