Journal of Clinical Oncology, Vol 15, 915-920, Copyright © 1997 by American Society of Clinical Oncology
Phase II study of trimetrexate, fluorouracil, and leucovorin for advanced colorectal cancer
CD Blanke, B Kasimis, P Schein, R Capizzi and M Kurman
Division of Medical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. charles.blanke@mcmail.vanderbilt.edu
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
(I.V.) on day 1, leucovorin 200 mg/m2 I.V. 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.
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