Multicenter phase II study to evaluate a 28-day regimen of oral fluorouracil plus eniluracil in the treatment of patients with previously untreated metastatic colorectal cancer

Purpose: To determine the efficacy of fluorouracil (5-FU) plus eniluracil when administered to patients with previously untreated metastatic colorectal cancer. Patients and Methods: In this single-arm phase II study, patients with previously untreated metastatic colorectal cancer received oral eniluracil plus 5-FU (10:1 dose ratio), at 5-FU doses of 1.00 mg/m² or 1.15 mg/m² twice daily (every 12 hours) for 28 consecutive days repeated every 5 weeks (one cycle). Treatment continued until there was documented disease progression or unacceptable toxicity. Results: Thirty and 25 patients were enrolled at a starting dose of 1.00 mg/m² and 1.15 and mg/m², respectively. Fourteen (25%) of 55 patients (95% confidence interval, 15% to 39%) had a partial response, and 20 patients (36%) had stable disease. The median durations of the partial responses and stable disease were 23.9 weeks (range, 12.3 to 52.1+ weeks) and 24.1 weeks (range, 17.1 to 55.6+ weeks), respectively. The median durations of progression-free and overall survival were 22.6 weeks (range, 21.0 to 29.0 weeks) and 59 weeks (range, 4 to 84+ weeks), respectively. The response rate in the 1.15 mg/m²-dose group was similar to the 1.00 mg/m²-dose group (28% v 23%, respectively). Severe (grade 3/4) nonhematologic treatment-related toxicity included diarrhea (nine patients), nausea/vomiting (one patient each), mucositis (two patients), and anorexia (one patient). Severe hematologic toxicities were rare. At the 1.15 mg/m²-dose level, two patients exhibited grade 3 granulocytopenia, and two patients had grade 3 anemia. Conclusion: The response rate with oral 5-FU plus eniluracil is comparable with that observed with infusional 5-FU or bolus 5-FU and leucovorin. The toxicity profile of this oral regimen is acceptable for use in an outpatient home-based setting. (C) 2000 by American Society of Clinical Oncology.