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 patients 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 chemotherapy regimen weekly for six courses every 8 weeks: trimetrexate 110 mg/m² intravenously (IV) an day 1, leucovorin 200 mg/m² IV on day 2 (24 hours later), 5FU 500 mg/m² on day 2 immediately following 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 response, and all 36 were assessable for toxicity. Two patients (7%) achieved 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 median survival duration for the entire cohort was 53.4 weeks. Gastrointestinal toxicity was most common, with 21 patients (58%) having grade 3/4 diarrhea and 12 patients (34%) grade 3/4 nausea. Hematologic toxicity was generally low grade, although two patients died of sepsis. Conclusion: 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.