BIMONTHLY HIGH-DOSE LEUCOVORIN AND 5-FLUOROURACIL 48-HOUR CONTINUOUS-INFUSION IN PATIENTS WITH ADVANCED COLORECTAL-CARCINOMA

BACKGROUND, It has been suggested that there is a relationship between 5-fluorouracil (5-FU) dose levels and response rates. A bimonthly 2-d ay regimen of leucovorin (LV) and 5-FU bolus infusion has been found t o be superior to a monthly 5-FU bolus with low dose LV. Based on these reports, a first-line Phase II study was performed in 101 patients wi th advanced colorectal carcinoma who were given a bimonthly combinatio n of high dose LV and a high dose 48-hour infusion of 5-FU. METHODS. T he selected regimen included a 2-hour infusion of LV 500 mg/m(2), on e ach of 2 consecutive days and a 48-hour infusion of 5-FU, 1.5 to 2 g/m (2)/24 hours starting after Day 1 of LV treatment every 2 weeks until there was evidence of disease progression. Evaluation was performed ev ery six cycles. This study reports the treatment of 101 patients with measurable disease. RESULTS, World Health Organization toxicity Grade 3-4 occurred in 15% of patients, nausea in 2%, diarrhea in 5.1%, mucos itis in 4%, neutropenia in 4% (Grade 4: 2%), hand-foot syndrome in 2%, alopecia in 4%, and encephalopathy in 1%. The overall response rate w as 33.7%. Five patients had a complete response (5%), and 29 had a par tial response (28.7%). In 45 patients disease was Stable (44.6%), and in 19 patients there was disease progression (18.8%). Three patients ( 3%) could not be evaluated. The median progression free survival was 8 months and median survival was 18 months. CONCLUSIONS. In the current study, bimonthly high dose LV and a high dose 48-hour infusion of 5-F U had activity in patients with advanced colorectal carcinoma. Toxicit y is notably low, and the regimen is suitable for use in combination w ith other drugs. (C) 1997 American Cancer Society.