INTRAAORTIC STOP-FLOW INFUSION - PHARMACOKINETIC FEASIBILITY STUDY OF REGIONAL CHEMOTHERAPY FOR UNRESECTABLE GASTROINTESTINAL CANCERS

Background: This study attempted to increase the exposure of gastrointestinal tract tissues to chemotherapy by prolonging the first pass of intraaortically administered drug by temporary occlusion of vascular structures. Methods: Bolus infusion of C-14-labeled mitomycin C (MMC) mixed with unlabeled MMC was performed in dogs. Distribution of MMC in gastrointestinal tract tissues was studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted the control group, Vascular flow was controlled in four ways for 30 min: type I-stop-flow infusion (SFI) with clamping of the abdominal aorta above the celiac and below inferior mesenteric artery; type II-with additional clamping of the inferior vena cava above the diaphragm; type III with additional clamping of the portal vein in the hepatoduodenal ligament; and type IV-with surgical exclusion of nongastrointestinal branches of the aorta in addition to type II clamping. Results: Type II and IV produced a 3-10-fold increase in exposure to MMC of major gastrointestinal tissues as compared with intravenous infusion. Area under the curve ratios with type IV were most prominent in the following tissues: stomach, pancreas, liver, and mesenteric lymph node. Conclusion: Access of MMC to several gastrointestinal tissues was increased through SFI. Type IV infusion was the most effective. Tissue exposure to MMC was especially advantageous for stomach, pancreas, liver, and mesenteric lymph node.