Phase II Study of Hepatic Artery Infusion with 5-Fluorouracil, Adriamycin, and Mitomycin C (FAM) in Liver Metastases from Colorectal Carcinoma

Abstract

The liver may be the predominant organ of involvement in more than 50% of patients with colorectal carcinoma who develop metastatic disease. Once colorectal carcinoma metastasizes to the liver, prognosis becomes ominous. Median survival for untreated patients can be expected to be about 6 months [8,13,17] and it has been stated that the length of survival depends on the extent of hepatic metastases even if bones, lungs, and liver are all involved [8]. Systemic 5-fluorouracil (5-FU) is of limited value, median survival being approximately 8 months [15]. Because hepatic metastases receive their main blood supply from the hepatic artery, one way of approach has been ligation of the hepatic artery. In nonrandomized studies a median survival of about 11 months has been reported with this technique [1, 10]. Another treatment modality has been the infusion of cytostatic drugs into the hepatic artery. 5-FU (F), 5-fluoro-deoxyuridine (FUdR), and mitomycin C (M) are extracted by the liver; hence intraarterial administration of these drugs allows for a greater concentration into the tumor-bearing organ with less systemic toxicity. It has also been shown that the systemic Adriamycin (A) level during hepatic artery infusion (HAI) is 25% lower than the corresponding systemic level with peripheral venous infusion, while hepatic venous anthracycline levels, which are one measure of intrahepatic drug concentration in the hepatic and tumor capillary bed, are consistently higher when the drug is given by the hepatic artery route [5]. Employing the FAM combination systemically a response rate of only 17% has been reported in measurable advanced colorectal carcinoma [7]. HAI with a combination of five drugs including FAM yielded a response rate of 56% in patients with liver metastases from colorectal carcinoma [2]. In a pilot feasibility study in our institution 34 patients with liver metastases from colorectal carcinoma were treated by HAI with FAM. Results in a smaller series of patients with a shorter follow-up have already been reported [16]. In this report results are summarized after a median follow-up of 28 months.