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.
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.
Authors: Loek A W de Jong; Fortuné M K Elekonawo; Philip R de Reuver; Andre J A Bremers; Johannes H W de Wilt; Frank G A Jansman; Rob Ter Heine; Nielka P van Erp Journal: Br J Clin Pharmacol Date: 2018-10-25 Impact factor: 4.335