HEPATIC ARTERIAL FLOXURIDINE AND LEUCOVORIN FOR UNRESECTABLE LIVER METASTASES FROM COLORECTAL-CARCINOMA

Background. We studied three new dose schedules of hepatic arterial in fusion of floxuridine (FUDR) and leucovorin and update survival analys is of a previously reported trial using these drugs by hepatic arteria l infusion for patients with hepatic metastases from colorectal carcin oma. Methods. Untreated patients with hepatic metastases from colorect al cancer were treated with three dose schedules: Group D, FUDR (0.3 m g/kg/day) and leucovorin (30 mg/m(2)/day) as a 14-day continuous infus ion through an implantable hepatic arterial pump alternating with a 4- week rest period; Group E, a lower dose of FUDR (0.25 mg/kg/day) and l eucovorin (30 mg/m(2)/day) as a 14-day infusion alternating with 2 wee ks of saline; and Group F, FUDR (0.3 mg/kg/day) with a lower leucovori n dose (15 mg/m(2)/day) for 2 weeks followed by a 2-week rest. Results . In 42 patients with unresectable hepatic metastases, the complete-pl us-partial response rate was 56%, with a median survival of 24.2 month s. Complete-plus-partial response rates for groups D, E, and F were 30 %, 54%, and 75%, respectively. Twelve percent of the 42 patients devel oped biliary sclerosis; the percentages of patients per group were 17% , 15%, and 6%, respectively. Updated median survival of the original 2 4 patients treated with FUDR and leucovorin by hepatic arterial infusi on and these 42 new patients (66 total) was 28.8 months. One-, two-, t hree-, four-, and five-year survival rates were 86%, 62%, 31%, 15%, an d 7%, respectively. Conclusions. Hepatic arterial chemotherapy with FU DR and leucovorin for patients with hepatic metastases from colorectal carcinoma yields a high response rate and 1- and 2-year survivals of 86% and 62%, respectively. Although a lower dose of leucovorin (15 mg/ m(2)) with FUDR produces a high response rate with less toxicity, befo re larger scale trials are initiated, further investigation is needed to reduce toxicity. A study of hepatic arterial dexamethasone with FUD R and leucovorin has been initiated for this purpose.