760 Methotrexate (MTX) and 5-fluorouracil (5-FU) in advanced colorectal cancer patients previously treated with adjuvant 5-FU

5-FU cytotoxicity may be increased through biochemical modulation with MTX. This can be important in patients who have already received 5-FU in the adjuvant setting. We have employed a combination regimen of MTX followed by 5-FU, with leucovorin (LV) rescue, in a series of patients with advanced disease. Pts were required to have symptomatic, measurable, inoperable lesions from colorectal cancer, recurring after adequate radical surgery of the primary tumor and adjuvant 5-FU + LV, concluded at least 3 months before recurrence. Pts received MTX, 250 mg/m 2 as a 2-hours i. v. infusion, followed by two doses of 5-FU, 500 mg/m 2 as i.v. bolus 1 hour and 21 hours after the end of methotrexate infusion. LV rescue, 15 mg orally every six hours for 7 times, was started 1 hour after the second 5-FU dose. The cycle was repeated every 2 weeks. Results Twenty-two pts entered the trial, and 21 were evaluable. An objective response was observed in one pt (4.8%), 7 pts (33.3%) obtained tumor regression Conclusions biochemical modulation with MTX does not seem a satisfactory mean to increase 5-FU activity, when the patient has been previously exposed to 5-FU plus LV.