REGIONAL CHEMOTHERAPY FOR COLORECTAL HEPATIC METASTASES - EVIDENCE FOR IMPROVED SURVIVAL WITH NEW DRUG-COMBINATIONS

Background: In patients with colorectal hepatic metastases, response r ates with hepatic arterial infusion (HAI) FUdR (5-Fluoro-2-deoxyuridin e) are significantly higher than with systemic fluoropyrimidines. We r eport a novel animal model of intrahepatic therapy for hepatic metasta sis for the study of methods to increase response rates and improve su rvival. Methods: BD-IX rats are injected intrasplenically with K12/TRb cells. When hepatic metastases are established, animals are treated w ith hepatic or systemic chemotherapy, and the response to treatment, s urvival, and cause of death is determined. Results: Significant respon ses were observed with low- and high-dose HAI FUdR (p = 0.03 and 0.001 , respectively). Only high-dose FUdR controlled hepatic disease. HAI F UdR alone did not prolong survival compared with control, but combinat ion systemic FUdR and HAI FUdR did (p = 0.04). Continuous HAI of eithe r 5-fluorouridine or mitomycin C has not previously been reported. The re was no significant difference in response to FUdR, 5-fluorouridine, or mitomycin C. However, combination HA bolus mitomycin C plus either HAI 5-fluorouridine or HAI mitomycin C showed synergy with improved s urvival compared with all other treatment groups (p < 0.0001). Conclus ions: The combination of bolus hepatic artery mitomycin C with either HAI mitomycin C or HAI 5-fluorouridine yields significant response rat es, and survival is improved by this novel combination therapy.