5-Fluorouracil: Synchronous Application of Continuous and Bolus Therapy in Heavily Pretreated Metastatic Colorectal Cancer: A Phase I/II Study

Abstract

Background: 5-Fluorouracil (5-FU) continues to be a basic drug of standard regimens for the treatment of metastatic colorectal cancer. The optimal dosing and application schedule is still under discussion. Preclinical and clinical data show synergistic activity of 5-FU bolus and continuously infused 5-FU. A synchronous combination of continuous and bolus 5-FU application was evaluated in patients with pretreated metastatic colorectal cancer. Patients and Methods: The chemotherapy regimen consisted of a 7-week, continuously applied 5-FU infusion combined with weekly 5-FU boli. The starting dose was 300 mg/m² for the 5-FU bolus and 150 mg/m²/24 h for the continuous infusion. A 2-week rest was allowed at the end of each cycle. The continuous infusion was administered by portable, battery-powered pumps via implanted Port-a-cath systems. In 23 patients 90 cycles were performed and evaluated. 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/m² 5-FU bolus and continuous infusions of 200 mg/m²/24 h. At this dose level, 6 out of 12 patients experienced WHO grade III diarrhea and 1 patient WHO grade III mucositis. No other WHO grade III/sol;IV toxicities, especially no hematological side effect, occurred. Three out of 12 patients experienced partial remissions with durations of 3, 8 and 9 months, respectively, at the recommended dose level; 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 tolerated and can be safely administered in an outpatient setting. This regimen is active in patients progressing with 5-FU-based schedules and should be evaluated in further studies.