A PHASE-II STUDY OF WEEKLY 24-HOUR INFUSION OF HIGH-DOSE 5-FLUOROURACIL AND LEUCOVORIN (HDFL) IN THE TREATMENT OF RECURRENT OR METASTATIC COLORECTAL CANCERS

Previous report suggested that weekly 24-hour infusion of high-dose 5- fluorouracil (5-FU) and leucovorin is a highly active and relatively l ow toxic regimen for the treatment of colorectal carcinoma (J Clin Onc ol 9: 625-30, 1991). This phase II study was conducted to test this im portant observation by a slightly modified regimen in a larger group o f patients. The weekly HDFL regimen consisted of 5-FU 2600 mg/m(2)/wee k and leucovorin 300 mg/m(2)/week (maximum 500 mg) in a 24-hour intrav enous infusion. Between February 1992 and December 1995, a total of 42 patients with non-resectable, recurrent or metastatic colorectal aden ocarcinoma were enrolled onto the study. Twenty-nine (69.0%) patients had prior exposure to lower-dose 5-FU. There were 22 men and 20 women with median age of 60 (20-75) years. They received a total of 855 and an average of 20.4 (4 to 65) courses of HDFL chemotherapy. Most patien ts were treated at outpatient clinics and the drugs were infused by an ambulatory pump system via a Port-A catheter. The median duration of follow-up was 22 months. ECOG Gr 2-3 stomatitis, diarrhea, nausea, and vomiting developed in 6 (14.3%), 6 (14.3%), 5 (11.9%), and 5 (11.9%) patients, respectively. Twenty (47.6%) patients had developed hand-foo t syndrome. There was no hematological toxicities except 3 (7.1%) pati ents developed ECOG Gr 1-2 leucopenia. The overall response rate was 4 2.9% (28%-59%, 95% C.I.) with 2 complete responses and 16 partial resp onses. Eight (61.5%; 31%-86%, 95% C.I.) of 13 patients, who had no pre vious 5-FU exposure, responded (1 complete response, 7 partial respons es). Ten (34.5%; 17%-54%, 95% C.I.) of 29 patients, who had had previo us lower-dose 5-FU exposure, responded (1 complete response and 9 part ial responses). The median duration of response was 5 months (1+ to 23 + months). The median overall survival of the whole group of 42 patien ts and the 18 responders was 10 and 22 months, respectively. Our data supported the original results of HDFL regimen in the treatment of col orectal cancers. HDFL regimen can be used either as first-line or seco nd-line treatment for non-resectable, recurrent or metastatic colorect al cancers.