Intermittent hepatic arterial infusion of high-dose 5FU on a weekly schedule for liver metastases from colorectal cancer

Abstract

Purpose: We performed phase I and II studies to examine the usefulness of intermittent hepatic arterial infusion of high-dose 5-fluorouracid (5-FU) for patients with liver metastasis from colorectal cancer. Methods: As the phase I study, 1000, 1250 and 1500 mg/m² of 5-FU were administered over 5 h by hepatic arterial infusion on a weekly schedule to establish the recommended dose. Based on the results of the phase I study, the phase II study was performed to confirm the efficacy of the recommended dose thus obtained. Results: In the phase I study, the dose-limiting factors of this therapy were gastrointestinal and central nervous system toxicities, and the recommended dose was judged to be 1000 mg/m². In the phase II study, 1000 mg/m² of 5-FU was administered over 5 h once a week on an outpatient basis, and this therapy was repeated as long as possible. The response rate was 78% (25/32), with an overall median survival time of 25.8 months (without extrahepatic lesions 25.9 months; with extrahepatic lesions 17.3 months). Conclusions: (1) Compared with conventional continuous infusion, the advantages of this therapy were that it caused no decrease in the patient's quality of life as a result of being permanently equipped with a pump and it thus enabled more cost-effective use of the pump, (2) The phase II study on 32 patients showed that this therapy caused no serious toxicities, with a response rate of 78% and a survival time of 25.8 months, which exceeded the results with conventional continuous infusion. If the reproducibility of these results is established in further studies involving multicenter collaboration, this therapy will be able to become the standard local chemotherapy for liver metastases from colorectal cancer. (3) Important problems remaining to be solved are improvement of the technical aspects and studies of combined use with systemic chemotherapy. Furthermore, to finally determine the position of this therapy in the treatment system for liver metastasis from colorectal cancer, it is necessary to conduct comparative trials versus systemic chemotherapy, using the survival time as the end-point.