Weekly 5-fluorouracil and leucovorin: Achieving lower toxicity with higher dose-intensity in adjuvant chemotherapy after colorectal cancer resection

Abstract

Background: Current standard therapy following resection of high-risk colon cancer is intravenous bolus 5-fluorouracil (5-FU) with leucovorin (LV), but there is no consensus on the optimum regimen of these drugs: practice ranges from the high toxicity Mayo Clinic schedule to the very low toxicity weekly QUASAR schedule. We present data for a weekly schedule that aims to provide moderately dose-intense treatment with low toxicity. Patients and methods: One hundred and sixty-two patients were studied: 60% male; median age 65 years (36% over 70 years); 94% colorectal primary. Treatment was intravenous bolus (5 min) 5-FU 425 mg/m2 plus D,L-LV 45 mg flat rate once weekly, for a planned 24 weeks. Data for toxicity, dose-reductions, delays and stop-pages were collected. Results: Overall, 20% of patients experienced any grade ≥3 toxicity, most commonly diarrhoea (14% patients). Dose reductions were made in 35% of patients (although only 21% required 20% or more reduction); toxicity contributed to a decision to stop treatment before 24 weeks in 16% of patients. Median delivered dose intensity (DI) was 96% of planned (407 mg/m2/week) during treatment, and 91% of planned (385 mg/m2/week) over the full 24 week treatment plan. Female sex and age >70 years were significantly associated with higher rates of toxicity and dose adjustment, and lower delivered DI. Conclusions: Weekly treatment at these doses is convenient and well-tolerated for the large majority of patients, and achieves DI comparable with the 5 days a month QUASAR schedule and other more toxic standard regimens. © 2004 European Society for Medical Oncology.