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In preclinical models, there appears to be additive or synergistic effects when combining 5\u2010Fluorouracil (5\u2010FU) with nonsteroidal anti\u2010inflammatory agents (NSAIDs) for the treatment of colorectal neoplasms. This data raised the question as to whether adding a COX\u20102 inhibitor to 5\u2010FU\u2010based regimens would increase the response rates with an acceptable toxicity profile in patients with metastatic colon cancer. In the current study, patients with metastatic colorectal cancer, who were either untreated or previously treated (more than 1 year ago) with adjuvant 5\u2010FU and Leucovorin (LV) received 5\u2010FU and LV (Mayo regimen) in addition to Rofecoxib. Tumor samples from all patients exhibited evidence of moderate COX\u20102 over\u2010expression. 4 patients entered on the study developed upper gastrointestinal bleeding (grade III). Other toxicities included grade II stomatitis (3 patients), grade II thrombocytopenia (1 patient), grade II diarrhea (2 patients) and grade I nausea (1 patient). There were no partial or complete responses in the first 10 patients entered on the study so the study was terminated (probability of success &lt; 0.3 with type 1 error of 0.05 and power of 0.8). Thus, Rofecoxib did not appear to increase antitumor activity and resulted in increased gastrointestinal toxicity when combined with 5\u2010FU\/LV. Future studies will need to consider the added gastrointestinal toxicity of Rofecoxib when combined with chemotherapy for the treatment of patients with colorectal cancer. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.11164","type":"journal-article","created":{"date-parts":[[2003,5,20]],"date-time":"2003-05-20T11:34:57Z","timestamp":1053430497000},"page":"868-872","source":"Crossref","is-referenced-by-count":50,"title":["Increased toxicity and lack of efficacy of Rofecoxib in combination with chemotherapy for treatment of metastatic colorectal cancer: A phase II study"],"prefix":"10.1002","volume":"105","author":[{"given":"Carlos R.","family":"Becerra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene 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