PHASE-II TRIAL OF HEPATIC ARTERIAL INFUSION OF FLUOROURACIL AND RECOMBINANT HUMAN INTERFERON ALFA-2B FOR LIVER METASTASES OF COLORECTAL-CANCER REFRACTORY TO SYSTEMIC FLUOROURACIL AND LEUCOVORIN

Purpose: To determine the toxicity, response rate, and survival in pat ients treated with hepatic arterial infusion (HAI) of fluorouracil (5- FU) plus recombinant human interferon alfa-2b (rIFN-alpha 2b) (Intron- A; Schering-Plough, Inc, Kenilworth, NJ) for colorectal carcinoma (CRC ) liver metastases refractory to systemic 5-FU plus leucovorin (LCV). Patients and Methods: Forty-eight patients were given a 6-hour HAI of rIFN-alpha 2b 5 MU/m(2) followed by an 18-hour HAI of 5-FU, 1,500 mg/m (2) daily for 5 days. Twenty-nine patients were treated through percut aneously placed catheters and 19 through implantable infusion pumps (S hiley Infusaid Inc, Noorwood, MA). Treatment cycles were repeated ever y 28 to 35 days. Results: There were three (6.6%) complete remissions (CRs) and 12 (26.6%) partial remissions (PRs), for a CR plus PR rate o f 33.3% among 45 assessable patients (95% confidence interval [CI], 20 % to 49%). The median response duration was 7 months, while median sur vival duration was 15 months. Grade 3 to 4 treatment-related toxic eff ects included mucositis (40%), neutropenia (42%), and thrombocytopenia (12%). No hepatobiliary toxicity was encountered in any of the patien ts. Treatment was discontinued because of progressive liver disease in 23 patients and extrahepatic progression in 16, while six patients co ntinue treatment through on Infusaid pump. Conclusion: HAI of 5-FU plu s rIFN-alpha 2b is well tolerated, devoid of hepatobiliary toxicity, a nd can produce a response rate of 33.3% among patients refractory to b olus intravenous (IV) 5-FU plus LCV. The lack of hepatobiliary toxicit y may permit salvage HAI with floxuridine (FUDR) in patients whose liv er tumors fail to respond to HAI of 5-FU plus rIFN-alpha 2b. Because d iarrhea was not a common side effect of HAI of 5-FU plus rIFN-alpha 2b , it would be of interest to investigate whether alternating HAI of 5- FU and rIFN-alpha 2b with systemic irinotecan (CPT-11) will decrease t he incidence of both hepatic and extrahepatic disease progression. (C) 1997 by American Society oi Clinical Oncology.