A simplified regimen of weekly high dose 5-fluorouracil and leucovorin as a 24-hour infusion in patients with advanced colorectal carcinoma

BACKGROUND. Reports of in vitro experiments in colorectal carcinoma cells s uggest that prolonged cellular exposure to 5-fluorouracil (5-FU) combined w ith relatively low concentrations of leucovorin (LV) provides optimal enhan cement of 5-FU efficacy. In this study, a simplified regimen of weekly 24-h our infusion of high dose 5-FU combined with a relatively low dose of LV wa s used to treat patients with advanced colorectal carcinoma. METHODS. Thirty-six patients with advanced colorectal carcinoma received 5- FU, 2600 mg/m2, admired with LV, 100 mg/m2, in a portable infusion pump adm inistered intravenously over a 24-hour period. High dose 5-FU/LV was delive red once a week for 5 consecutive weeks followed by a 1-week recovery perio d. All patients were assessable for toxicity and response. RESULTS, Two complete responses and 15 partial responses were observed (res ponse rate of 47.2%; 95% confidence interval, 30.1-64.4%). The median respo nse duration was 9.6 months. The median survival and time to progression we re 11.9 months and 7.1 months, respectively. The toxicity was mild and acce ptable. The major dose-limiting factors were hand-foot syndrome and fatigue . CONCLUSIONS. This simplified regimen of weekly 24-hour continuous infusion of high dose 5-FU/LV is an effective regimen in the treatment of patients w ith advanced colorectal carcinoma. Further study of the pharmacokinetics of combination therapy with 5-FU and LV as used in this regimen and its corre lation with response and toxicity is warranted. (C) 1999 American Cancer So ciety.