SHORT-TERM INTRAHEPATIC FUDR INFUSION COMBINED WITH BOLUS MITOMYCIN-C- REDUCED RISK FOR DEVELOPING DRUG-RESISTANCE

This study evaluates tumor response, survival, and development of resi stance to HAI chemotherapy, comparing a combination of bolus MMC and s hort duration FUdR to short duration FUdR alone or to long duration FU dR alone, using a rat hepatic metastases model. After intrasplenic inj ection of 10(7) K12/TRb colon cancer cells in BD-IX rats on day 0, hep atic metastases were evaluated and HA catheters were placed on day 14. The response was determined on day 28. Chemosensitivity of the hepati c metastases after HAI treatments was determined using the MTT assay. Bolus MMC with short duration FUdR as well as long-term FUdR alone pro vided better hepatic tumor response and survival than short-term FUdR alone. However, bolus MMC with short duration FUdR decreased the acqui red resistance to FUdR, compared to long-term FUdR, without causing re sistance to MMC. These results provide a rationale for using short dur ation of FUdR in combination with other drugs. (C) 1994 Wiley-Liss, In c.