[Therapeutic effect of sequential doses of methotrexate (MTX) and 5-fluorouracil (5-FU) in advanced gastric cancer: comparison of intermediate-dose MTX with high-dose MTX]

Abstract

Twenty-one patients were treated with sequential doses of MTX and 5-FU so as to be classified by MTX dosage into an intermediate MTX-dose group and a high MTX-dose group. In the intermediate-dose MTX group, the drug was given at a dosage of 100 mg/m2 intravenously (i.v.) and followed 1 hour later by 5-FU at 800 mg/m2 i.v. (dripping for 1 hour); the drugs were recycled every 1 week. In the high-dose MTX group, the drug was administered at a dose of 1.5 g/m2 i.v. (dripping for 2 hours) and followed 1 hour later by 5-FU at 1.5 g/m2 i.v. (dripping for 2 hours); the drugs were recycled every 2-3 weeks. Average MTX concentrations in serum at the start of 5-FU administration were 1.69 X 10(-5) and 1.33 X 10(-4) mol/l/h in the intermediate and high-dose MTX groups, respectively. Six (50%) of 12 patients adequately treated with intermediate-dose MTX had a partial response (PR), and one (14.3%) of 7 evaluable patients treated with high-dose MTX had a PR. Major toxicity included diarrhea (33.3%) in the intermediate-dose MTX group and hair loss (71.4%) in the high-dose MTX group. Hematological toxicity was mild in MTX group: six (50%) of 12 patients had a granulocyte count nadir less than 1,000/microliters and one (8.3%) of 12 patients had a platelet count nadir less than 10(5)/microliters in the intermediate-dose MTX group. Five (71.4%) of 7 patients had a granulocyte nadir less than 1,000/microliters and two (28.6%) of 7 patients had a platelet count nadir less than 10(5)/microliters in the high-dose MTX group.