High-dose methotrexate and 5-fluorouracil in patients with advanced colorectal carcinoma. A randomized study of two pretreatment intervals

Thirty-two patients with untreated advanced colorectal carcinoma received high-dose methotrexate pretreatment followed sequentially by 5-fluorouracil (5-FU). Patients were randomized to receive high-dose methotrexate pretreatment at one of two intervals (0 h or 3 h before 5-FU). There were 16 patients in each study arm. The median methotrexate dose was 1,000 mg/m² (range, 600-1,200 mg/m²) and that of 5-FU was 1,000 mg/m² (range, 800-1,200 mg/²). Treatments were repeated every 21 days. Three patients achieved partial remission (1 in the 3-h interval arm and 2 in the 0-h interval arm). As the response rate using this regimen was noted to be 9% with a <5% chance of achieving a response rate higher than 20%, we terminated this study although the therapy resulted in mild-to-moderate but infrequent toxicity. We thus conclude that pretreatment with high-dose methotrexate given at short intervals followed by 5-FU has no significant activity against colorectal carcinoma.