Purpose: To evaluate the activity and safety of an alternating schedule of irinotecan (CPT-11) with high-dose 5-fluorouracil (5-FU) given as a weekly 48-hour infusion in combination with leucovorin (LV) in the first-line treatment of metastatic colorectal cancer (MCRC) patients. Patients and Methods: We tested the activity of a regimen consisting of a four times per week schedule of high-dose LV (150 mg/m2) followed by a 48-hour 5-FU infusion (2,600 mg/m2) alternated with CPT-11 (350 mg/m2). An alternating cycle was to be performed every 8 weeks. Treatment was administered until disease progression, unacceptable toxicity or patient refusal occurred. Thirty-five consecutive patients with measurable MCRC, aged 18–80, with a performance status ≤2, were entered into our study from May 1998 to January 2000. Results: Four complete and 9 partial responses were observed (objective response rate was 37%; 95% confidence interval, CI: 21.5–55.1%); an additional 46% of the patients had stable disease. The median duration of response was 6.2 months, median time to progression 8 months (95% CI: 5.9–10.1%), and overall survival was 18.5 months (95% CI: 15.1–21.9%). The 1-year survival was 68%. No toxic deaths occurred. The incidence of grade 3–4 toxicity per patient in any cycle was: mucositis 9% and diarrhea 11% for the infusional 5-FU part, nausea/vomiting 3%, diarrhea 14%, and neutropenia 43% for the CPT-11 part of regimen. Conclusions: Our alternating schedule of 5-FU/LV and CPT-11 is a well-tolerated outpatient treatment as front-line therapy for MCRC with comparable efficacy to regimens with both drugs given together.

Keywords:
Alternating regimen, Colorectal cancer, 5-Fluorouracil, Irinotecan, Leucovorin
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© 2002 S. Karger AG, Basel
2002
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