Sequential methotrexate and 5-fluorouracil as second-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 methotrexate (MTX) and 6-S leucovorin (LV) seems mainly directed at mio different intracellular targets, supporting the hypothesis of possible non-cross resistance between these two methods of 5-FU potentiation. Thirty-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 and 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 Partial Remissions (PR) were achieved (Response Rate=6.6%; 95% Confidence Interval 0%-14%). Eight patients had disease stabilization (SD). The overall median survival was 5 months (range 1-11). No WHO grade III-IV toxicities were reported. Despite the good tolerability, this combination of MTX, 5-FU and LV rescue has minimal activity in ACC after the failure of 5FU+LV-based chemotherapy.