SEQUENTIAL METHOTREXATE AND 5-FLUOROURACIL AS 2ND-LINE CHEMOTHERAPY FOR ADVANCED COLORECTAL-CANCER PATIENTS PRETREATED WITH 5-FLUOROURACIL AND LEUCOVORIN - A GISCAD STUDY

The biochemical modulation of 5-fluorouracil (5-FU) by means of methot rexate (MTX) and 6-S leucovorin (LV) seems mainly directed at mio diff erent intracellular targets, supporting the hypothesis of possible non -cross resistance between these two methods of 5-FU potentiation. Thir ty-one patients, all previously treated with 5-FU and LV for advanced colorectal cancer (ACC), were treated with MTX=200 mg/m(2) iv day 1 an d 5-FU 600 mg/m(2) day 2 with 6-S LV 10 mg/m(2) po q 6 h X 6 starting 24 h after MTX, repeated every 2 weeks. Of 30 evaluable patients, 2 Pa rtial Remissions (PR) were achieved (Response Rate=6.6%; 95% Confidenc e Interval 0%-14%). Eight patients had disease stabilization (SD). The overall median survival was 5 months (range 1-11). No WHO grade III-I V toxicities were reported. Despite the good tolerability, this combin ation of MTX, 5-FU and LV rescue has minimal activity in ACC after the failure of 5FU+LV-based chemotherapy.