Sequential methotrexate, 5-fluorouracil, and calcium leucovorin in colorectal carcinoma.

Forty-four patients with locally recurrent or metastatic colorectal adenocarcinoma were treated with methotrexate (MTX) 100 mg/m2 i.v. followed 1 h later by 5-fluorouracil (5-FU) 600 mg/m2 i.v. Calcium leucovorin 10 mg/m2 p.o. q 6 h X four doses was given 24 h after MTX. The regimen was given on days 1 and 8 and repeated every 28 days. Six of 44 patients (14%) obtained either complete or partial response with a mean response duration of 6.8 months. Of 26 previously untreated patients there were one complete response (4%), four partial responses (15%), and 12 (46%) instances of stabilization of disease. Patients obtaining response or stabilization of disease experienced improved survival compared to those with progressive disease. Toxicity consisted of stomatitis and hematopoietic suppression requiring dose attenuation in six patients (14%); there were no treatment-related deaths. Sequenced MTX/5-FU is modestly active with acceptable toxicity in previously untreated patients with colorectal adenocarcinoma but offers no apparent advantage over single-agent 5-FU.