5-fluorouracil: Synchronous application of continuous and bolus therapy inheavily pretreated metastatic colorectal cancer: A phase I/II study

Background: 5-Fluorouracil (5-FU) continues to be a basic drug of standard regimens for the treatment of metastatic colorectal cancer. The optimal dos ing and application schedule is still under discussion. Preclinical and cli nical data show synergistic activity of 5-FU bolus and continuously infused 5-FU. A synchronous combination of continuous and bolus 5-FU application w as evaluated in patients with pretreated metastatic colorectal cancer. Pati ents and Methods:The chemotherapy regimen consisted of a 7-week, continuous ly applied 5-FU infusion combined with weekly 5-FU boli. The starting dose was 300 mg/m(2) for the 5-FU bolus and 150 mg/m(2)/24 h for the continuous infusion. A 2-week rest was allowed at the end of each cycle. The continuou s infusion was administered by portable, battery-powered pumps via implante d Port-a-cath systems. In 23 patients 90 cycles were performed and evaluate d. All patients had been pretreated with one or more 5-FU-based schedules. Results: Diarrhea, nausea and vomiting were the most frequent side effects. The recommended dose was the combination of 400 mg/m(2) 5-FU bolus and con tinuous infusions of 200 mg/m(2)/24 h. At this dose level, 6 out of 12 pati ents experienced WHO grade III diarrhea and 1 patient WHO grade III mucosit is. No other WHO grade III/IV toxicities, especially no hematological side effect, occurred. Three out of 12 patients experienced partial remissions w ith durations of 3, 8 and 9 months, respectively, at the recommended dose l evel; 9 patients had progressive disease. Four additional patients at lower dose levels showed disease stabilization. The median overall survival was 6 months after the start of the study treatment. Conclusion: 5-FU given as a synchronous application of bolus and continuous infusion is well tolerate d and can be safely administered in an outpatient setting. This regimen is active in patients progressing with 5-FU-based schedules and should be eval uated in further studies.