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SutantoWard E , Arisawa Y , Tremiterra S , Sigurdson ER
Regional chemotherapy for colorectal hepatic metastases: Evidence for improved survival with new drug combinations
Annals of Surgical Oncology. 1996 Jan;3(1) :36-43
PMID: ISI:A1996TP42500006   
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Background: In patients with colorectal hepatic metastases, response rates with hepatic arterial infusion (HAI) FUdR (5- Fluoro-2-deoxyuridine) are significantly higher than with systemic fluoropyrimidines. We report a novel animal model of intrahepatic therapy for hepatic metastasis for the study of methods to increase response rates and improve survival. Methods: BD-IX rats are injected intrasplenically with K12/TRb cells. When hepatic metastases are established, animals are treated with hepatic or systemic chemotherapy, and the response to treatment, survival, and cause of death is determined. Results: Significant responses were observed with low- and high-dose HAI FUdR (p = 0.03 and 0.001, respectively). Only high-dose FUdR controlled hepatic disease. HAI FUdR alone did not prolong survival compared with control, but combination systemic FUdR and HAI FUdR did (p = 0.04). Continuous HAI of either 5-fluorouridine or mitomycin C has not previously been reported. There 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 survival compared with all other treatment groups (p < 0.0001). Conclusions: The combination of bolus hepatic artery mitomycin C with either HAI mitomycin C or HAI 5-fluorouridine yields significant response rates, and survival is improved by this novel combination therapy.
Times Cited: 2 English Article TP425 ANNALS SURG ONCOLOGY