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.
Gastric ulceration developed in eight patients during intrahpeatic arterial infusion of 5-FU. Bleeding occurred in four instances and perforation in one. In all cases the catheter tip had been dislodged and was proximal to its correct position, allowing the stomach to be directly infused with 5-FU. No duodenal ulcers were noted. All patients were symptomatic for several days before the diagnosis was made. Of 20 patients with catheter dislodgement, five had documented ulcers, three had upper gastrointestinal bleeding of undetermined etiology, eight had epigastric pain or vomiting and only four were asymptomatic. Prompt determination of catheter position is necessary in patients receiving intrahepatic arterial infusion of 5-FU if symptoms consistent with gastric ulceration occur. Gastric ulcers should be vigorously treated because of the high rate of complications in patients receiving chemotherapy.
A total of 419 patients with progressive liver disease, in nearly all cases metastatic from gastrointestinal primaries, were treated by intrahepatic arterial infusion with 5-FU. Three-fourths of these patients h a d had prior trials with intravenous 5-FU for 1 or 2 months to several years a n d had been switched to the infusion upon the development of progression. Catheters were placed percutaneously a n d the patients infused with 5-FU a t a dose of 20 to 30 mg/ kg/day X 4, then 15 mg/kg/day x 17, a t which point the catheter was removed a n d the patient sent home o n weekly i.v. doses a t 15 mg/kg. Toxicity, morbidity, a n d mortality were minimal with the intrahepatic arterial infusion treatment a n d the rigid criteria of improvement were met by 55% of the study cases. T h e survival rate of those patients who responded to the treatment was greater than the survival rate of those who failed t o respond.Cancer 1975. ATlENTS WITH PROGRESSIVE LIVER METASTASESP of gastrointestinal origin have a poor prognosis. Although the survival time of cases with liepa tic spread from large bowel cancer has been reported to be longer than with metastases from other gastrointestinal primaries,fi the mean survival time of those with untreated liver involvement is only 5 to 7 rnonths.4~~ Approximately 15% to 20% of patients with colorectal cancer have responded to 5-fluorouracil (5-FU);1-2 however, no effective intravenous treatment has been developed for those patients who fail to respond to 5-FU. These considerations have led to a continuing interest in the treatment of liver metastases with intrahepatic arterial infusion therapy.G-7~*.9 The favorable results of our earlier study with intraarterial infusion with 5-FU in 200 patients have encouraged us to expand that experience.3 MATERIALS AND METHODSThree-fourths of the 419 patients treated over the past decade with intrahepatic arterial infusion had prior trials with intravenous
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