Dw. Dietz et al., VASOPRESSIN SELECTIVELY INCREASES 5-FLUOROURACIL UPTAKE BY COLORECTALLIVER METASTASES FOLLOWING HEPATIC-ARTERY BOLUS INFUSION, The Journal of surgical research (Print), 77(2), 1998, pp. 150-156
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.