A PHASE-II STUDY OF REGIONAL 5-FLUOROURACIL INFUSION WITH INTRAVENOUSFOLINIC ACID FOR COLORECTAL LIVER METASTASES

Regional chemotherapy, delivered via the hepatic artery, may significa ntly increase tumour response rates in patients with colorectal liver metastases. However, survival is limited by extrahepatic disease progr ession. We have developed a novel therapeutic approach for patients wi th metastases confined to the liver. In order to achieve high local re sponse rates and also inhibit extrahepatic progression, 5-fluorouracil (5-FU) was infused intra-arterially at a dose previously calculated t o achieve both high-dose regional therapy and adequate systemic levels . To enhance efficacy further, 5-FU was combined with high-dose system ic folinic acid (FA). Thirty-one patients were evaluated in a phase II study. 5-FU (1.5 g m(2)) was infused via a surgically implanted hepat ic artery catheter over a 24 h period; FA (total 400 mg m(-2)) was inf used intravenously during the initial and final 2 h. Treatments were g iven weekly for cycles of 6 weeks' duration. To date, median duration of treatment is 6 months and the median follow-up period is 17 months. The overall response rate was 48% with two complete and 13 partial re sponses. Predicted median time to progression is 8 months. The site of first progression was hepatic in 10 (42%) and extrahepatic in 14 (58% ) patients. Seven patients developed local complications; one required emergency surgery. Side-effects were limited to grade 3 toxicity (fou r patients) or less. Predicted median survival is 19 months. This appr oach, which is associated with a high response rate and low systemic t oxicity, warrants further evaluation. A phase III study is planned.