Phase II study of weekly 24-hour intra-arterial high-dose infusion of 5-fluorouracil and folinic acid for liver metastases from colorectal carcinomas

Background: A multicenter phase II trial was initiated in order to evaluate the weekly, high-dose 24-hour infusion of 5-fluorouracil (5-FU) plus folin ic acid (FA) in patients with unresectable colorectal cancer hepatic metast ases. Patients and methods: A weekly hepatic arterial infusion (HAI) of FA 500 mg /m(2) followed by a 24-hour infusion of 5-FU 2,600 mg/m(2) (later reduced t o 2,200 mg/m(2)) was given via a surgically implanted intra-arterial port s ystem. One treatment cycle consisted of six weekly applications followed by a two-week rest period. Toxicity was assessed according to the WHO criteri a. Chemotherapy was continued until disease progression or complete respons e occured. Results: A total of 50 patients (40 chemonaive, 10 pretreated) entered this trial. An objective tumor response occurred in 28 patients (56%), while 13 patients (26%) had stable disease. The median progression free survival wa s 12 months, and the median survival 22.3 months. Due to a high rate of gas trointestinal side-effects in the initial phase of the trial, the dosage of 5-FU was reduced to 2,200 mg/m(2) for all subsequent patients. Diarrhea an d nausea led to a dose reduction in 40% of applications and 24% of patients , respectively. One patient died of cardiac insufficiency unrelated to chem otherapy before response evaluation. Conclusions: This HAI approach using high-dose 5-FU was relatively well tol erated when 2,200 mg/m(2) instead of 2,600 mg/m(2) was used. The activity o f this regimen is promising and warrants further evaluation and modificatio n.