VASOPRESSIN SELECTIVELY INCREASES 5-FLUOROURACIL UPTAKE BY COLORECTALLIVER METASTASES FOLLOWING HEPATIC-ARTERY BOLUS INFUSION

Background. Poor drug uptake secondary to the hypovascularity of color ectal liver metastases may partially explain their limited response to hepatic artery chemotherapy. Vasoconstrictors can increase tumor perf usion but their effect on drug uptake has not been well-characterized. The aim of this study was to determine whether vasopressin could sele ctively increase tumor uptake of 5-FU. Materials and methods. A syngen eic rat model of colorectal liver metastases was used. Control group r ats under went a 60-s hepatic artery infusion of C-14-5-FU (30 mCi/150 mu L). Treatment group rats had vasopressin (60 mIU/kg, dose determin ed in pilot study) added to the 14C-5-FU infusion. Mean systemic arter ial pressure was minimally affected. Tumor:liver (Tn UR) and tumor cen ter:periphery (C/P UR) 5-FU uptake ratios were determined using quanti tative autoradiography techniques. Differences in tumor size (< or > 4 mm) and location (superficial vs deep) were accounted for. Statistica l analysis was by repeated measures ANOVA (P = 0.01 significant). Resu lts. A total of 161 tumors in 18 rats was analyzed. Tn URs were signif icantly higher in the treatment group compared to controls for tumors <4 mm (1.72 +/- 0.14 vs 0.70 +/- 0.16, P < 0.001), tumors >4 mm (0.99 +/- 0.15 vs 0.45 +/- 0.16, P = 0.01), deep tumors (1.17 +/- 0.13 vs 0. 68 +/- 0.15, P = 0.01), and superficial tumors (1.54 +/- 0.15 vs 0.47 +/- 0.17, P < 0.001), C/P URs did not differ significantly between the groups. Conclusions. The results of this study show that vasopressin selectively enhances the uptake of 5-FU by colorectal liver metastases in a rat model of hepatic artery infusion. This may represent a promi sing strategy for improving tumor response rates and patient survival. (C) 1998 Academic Press.