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Annals of Oncology 15:568-573, 2004
© 2004 European Society for Medical Oncology

Original Paper

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

Received 18 September 2003; revised 18 November 2003; accepted 22 December 2003

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 stoppages 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.

K. Patel, D. A. Anthoney, A. M. Crellin, D. Sebag-Montefiore, J. Messruther and M. T. Seymour*

Cancer Research UK Clinical Centre, Cookridge Hospital Leeds, Leeds LS16 6QB, UK

Key words: adjuvant, colorectal, dose intensity, fluorouracil, leucovorin, toxicity


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