Sequential trimetrexate, 5-fluorouracil and folinic acid are effective andwell tolerated in metastatic colorectal carcinoma

Trimetrexate (TMTX) is a new antifolate which avoids competition for cellul ar uptake with folinic acid (FA). A regimen of sequential TMTX, FA and 5-fl uorouracil (5-FU) has shown efficacy in patients with colorectal cancer. Th erefore, we treated 34 previously untreated patients with metastatic colore ctal cancer with a weekly chemotherapy regimen consisting of 110mg/m(2) of TMTX intravenously, then 24 h later 200 mg/m(2) of FA (i.v.) and 500 mg/m(2 ) of 5-FU (i.v.). Thereafter, 7 doses of oral FA (15 mg) were given at 6-ho urly intervals. A treatment cycle consisted of 6 weeks of treatment, then 2 weeks of rest. All patients were treated as outpatients unless complicatio ns arose. Thirty-three patients were assessable for tumor response, and all 34 patients were assessable for toxicity. Twelve patients (36%; 95% confid ence interval: 25-49%) achieved a partial response. The median duration of response was 8.5 months, and median survival was 14 months. The most common toxicity was diarrhea of grade 3/4, observed in 22% of treatment cycles; t his decreased to 8% with early loperamide treatment. Hematologic toxicity w as mild. The sequential administration of TMTX, FA and 5-FU is an active re gimen in the first-line treatment of metastatic colorectal cancer and warra nts further studies. Copyright (C) 2000 S. KargerAG, Basel.