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Tegafur/Uracil + Calcium Folinate in Colorectal Cancer

Double Modulation of Fluorouracil

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Abstract

The oral chemotherapeutic agent tegafur/uracil (UFT®) is the first of a new class of anticancer drugs called dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines. Tegafur/uracil combines uracil with the fluorouracil prodrug tegafur in a 4: 1 molar ratio. Uracil competitively inhibits the degradation of fluorouracil, which results in the concentration of fluorouracil remaining at sustained levels in both plasma and tumour. Tegafur/uracil has been commercially available in Japan since 1983 and examined extensively in various tumours. Trials conducted in the US have focused on the combination of tegafur/uracil plus calcium folinate (calcium leucovorin) [ORZEL®]. Several phase I and II trials have evaluated the maximum tolerated dose, pharmacokinetics, efficacy, and safety of this combination in the treatment of colorectal cancer. Results have shown that tegafur/uracil at 300 mg/m2/day in divided doses given every 8 hours for 28 days provides prolonged exposure to fluorouracil. Furthermore, tegafur/uracil + calcium folinate is well tolerated, with dose-limiting toxicity manifesting as diarrhoea. Compared with intravenous fluorouracil plus folinic acid (leucovorin) regimens, tegafur/uracil + calcium folinate has similar efficacy with less toxicity and is more convenient because it is an oral regimen. Early studies have also shown potential cost savings because of fewer complications.

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Paulo M. Hoff & Yvonne Lassere

  2. Division of Oncology Drug Products, Food and Drug Administration, 5600 Fishers Lane, HFD-150, Rockville, Maryland, 20857, USA

    Richard Pazdur

Authors
  1. Paulo M. Hoff
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  2. Yvonne Lassere
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  3. Richard Pazdur
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Correspondence to Richard Pazdur.

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Hoff, P.M., Lassere, Y. & Pazdur, R. Tegafur/Uracil + Calcium Folinate in Colorectal Cancer. Drugs 58 (Suppl 3), 77–83 (1999). https://doi.org/10.2165/00003495-199958003-00011

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