PHASE-II STUDY OF TRIMETREXATE, FLUOROURACIL, AND LEUCOVORIN FOR ADVANCED COLORECTAL-CANCER

Purpose: A phase II study to evaluate the response rate and toxicities of a trimetrexate, fluorouracil (5FU), and leucovorin regimen in pati ents with advanced incurable colorectal cancer. Patients and Methods: Thirty-six patients with unresectable or metastatic colorectal cancer who had not been treated for advanced disease received the following c hemotherapy regimen weekly for six courses every 8 weeks: trimetrexate 110 mg/m(2) intravenously (IV) on day 1, leucovorin 200 mg/m(2) IV on day 2 (24 hours later), 5FU 500 mg/m(2) on day 2 immediately followin g leucovorin, and oral leucovorin 15 mg every 6 hours for seven doses starting 6 hours after 5FU. Patients were treated until progression or unacceptable toxicity. Results: Thirty patients were assessable for r esponse, and all 36 were assessable for toxicity. Two patients (7%) ac hieved a complete response (CR) and 13 (43%) a partial response (PR), for an overall response (OR) rate of 50% (95% confidence interval [CI] , 32% to 68%). Analysis by intent to treat demonstrated a 42% OR rate (95% CI, 26% to 58%). At final analysis, 16 patients were alive. The m edian survival duration for the entire cohort wets 53.4 weeks. Gastroi ntestinal toxicity was most common, with 21 patients (58%) having grad e 3/4 diarrhea and 12 patients (34%) grade 3/4 nausea. Hematologic tox icity was generally low grade, although two patients died of sepsis. C onclusion: The combination of trimetrexate with 5FU and leucovorin is active in metastatic colorectal cancer. Gastrointestinal toxicity with this regimen is most prominent, but is manageable. (C) 1997 by Americ an Society of Clinical Oncology.