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  • Title: Regional chemotherapy for colorectal hepatic metastases: evidence for improved survival with new drug combinations.
    Author: Sutanto-Ward E, Arisawa Y, Tremiterra S, Sigurdson ER.
    Journal: Ann Surg Oncol; 1996 Jan; 3(1):36-43. PubMed ID: 8770300.
    Abstract:
    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 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.
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