A PILOT-STUDY ON INTENSIVE WEEKLY 24-HOUR INTRAARTERIAL INFUSION WITH5-FLUOROURACIL AND FOLINIC ACID FOR COLORECTAL LIVER METASTASES

Purpose: A pilot study was performed to evaluate the tolerance and eff icacy of a hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) an d folinic acid (FA) in patients with unresectable liver metastases fro m colorectal carcinoma, Patients and Methods: In 11 patients, 135 appl ications of high-dose HAI of 5-FU/FA were administered, All patients h ad been intra-arterially pretreated, and 2 of them had received an add itional intravenous therapy. The chemotherapy regimen consisted of a w eekly HAI of FA 500 mg/m(2) over 1 h, immediately followed by HAI of 5 -FU over 24 h, Four patients received a 5-FU starting dose of 2,000 mg /m(2) and 7 patients of 2,400 mg/m(2). One course consisted of 12 week ly applications interrupted by 1 week after 6 applications and 4 weeks after 12 applications. Results: The applied regimen caused only mild side effects, Nausea and vomiting were the most frequently side effect s with 36 episodes out of 135 applications (WHO grade greater than or equal to 3: 2 episodes), Diarrhea was a minor problem occurring with 8 episodes (WHO grade greater than or equal to 3: 1 episode), There was no evidence of myelosuppression, hand-foot syndrome, neurotoxicity, a nd biliary sclerosis, A partial remission was observed in 3 patients, and a disease stabilization in 2 patients while the disease progressed in 6 patients under high-dose HAI of 5-FU/FA. Conclusion: The present pilot study demonstrates that the weekly high-dose HAI of 5-FU/FA is well tolerated and associated with very mild toxicity, Because of the encouraging response rate in patients, whose disease progressed under the conventional intra-arterial therapy either with 5-FU/FA or 5-fluor odeoxyuridine, this regimen seems to be an effective second-line treat ment and should be evaluated in nonpretreated patients in a phase II s tudy.