Intrahepatic arterial infusion with 5-fluorouracil

Abstract

Since 1964, 200 patients were treated with intra‐arterial 5‐FU infusion. Of them, 127 failed with intravenously injected 5‐FU, and 27 were unsuitable for such treatment as their involvement was so far advanced as to have jaundice due to extensive parenchymal involvement. In all but 12 patients, the catheter was placed percutaneously through the brachial artery. The criteria for improvement included at least a 6‐cm decrease in distance of the liver edge from the xiphoid or costal margin, a 50% decrease in the abnormal enzyme studies, a return of elevated bilirubin levels to normal so that jaundice disappeared, and all these responses continued for at least 2 months. Inpatients were treated with 5‐FU, 25 mg/kg/day × 4, then 15 mg/kg/day for 7 or 8 days. If no toxicity appeared, the 5‐FU was then increased to 20 mg/kg/day until the total infusion period was 21 days, and the catheter was removed. Outpatients received 500 mg daily in 140 ml 5% dextrose and 2,500 units heparin daily for 90 days, and then the catheter was removed. Following the termination of the infusion, the patient was given weekly intravenous doses of 5‐FU at 15 mg/kg. After several months, with reactivation of the disease, the intra‐arterial infusion was repeated. Minimal toxicity occurred, and there was one death from the procedure. Morbidity in the forms of infection and hemorrhage did occur, but, in the last 100 patients, there were only 2 minor infections. Of 113 study patients, 69 (61%) met our criteria of improvement and had a median survival of 8.7 months. Forty‐four (39%) failed, and their median survival was 2.5 months. This demonstrates a significantly increased survival in the responders.

The blood supply of colorectal liver metastases

“…These theories have led over the years to the development of hepatic artery ligation and various forms of cytotoxic perfusion techniques in the treatment of multiple colorectal liver metastases (Brennan et al, 1963;Almersjo et al, 1968Almersjo et al, , 1972Watkins et at., 1970;Murray-Lyon et al, 1970;Ansfield et al, 1971;Fortner et al, 1973;Ansfield, 1975). Unfortunately, the results of these techniques in improving symptom-free survival have been particularly disappointing and unpredictable.…”

Bile duct strictures associated with hepatic arterial infusion chemotherapy

“…Hepatic arterial infusion chemotherapy has been used for 2 decades to treat liver metastases from colon carcinoma [1][2][3][4][5][6][7][8]. Liver tumors derive their blood supply primarily from hepatic arteries rather than portal veins.…”

Continuous 5-day regional chemotherapy by 5-fluorouracil in colon carcinoma: Pharmacokinetic evaluation

“…Locoregional chemotherapy has the dual aim of increasing the exposure of tumor-bearing areas to drugs while partially reducing the cytotoxic effects on the patient's healthy tissues (Ansfield et al, 1971;Ensminger et al, (1978). The recent interest shown in this therapeutic approach can be explained by better knowledge about pharmacokinetics, allowing more objective and rational use of drugs (Balis et al, 1983;Schabel et al, 1983) and by biotechnological progress in the field of implantable pumps (Blackshear et al, 1972) permitting chemotherapy infusions on an ambulatory basis.…”

“…Long clinical experience has been gained with chemotherapy protocols administered by an intra-arterial hepatic (i.a.h.) route (Ansfield et al, 1971;Stagg et al, 1984;Ensminer et al, 1978). Use of the portal vein appears advisable for small liver metastases (Ackerman et al, 1969).…”