Pharmacology of perioperative 5-fluorouracil.

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.