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Clinical Development of Eniluracil/Fluorouracil: an Oral Treatment for Patients with Solid Tumors

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Abstract

Eniluracil (776C85, GW776) inactivatesdihydropyrimidine dehydrogenase (DPD), the principal enzyme of5-fluorouracil (5-FU) catabolism. Inactivation of DPD eliminatesa potential mechanism for tumor 5-FU resistance and permitsachievement of reliable and predictable pharmacokincticsfollowing oral 5-FU administration. Eniluracil/5-FU hasdemonstrated efficacy as monotherapy in patients with a varietyof solid tumors when given on a 5 or 28-day dosing schedule. Theprimary and dose-limiting toxicity is myelosuppresion with the5-day schedule and diarrhea with the 28-day schedule. Thefrequency of hand-foot syndrome is minimal with either schedule.Phase III pivotal registration-directed studies witheniluracil/5-FU given by the 28-day schedule are ongoing orplanned for the near future in patients with advanced colorectal,breast and pancreatic cancer.

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  1. Glaxo Wellcome, Inc., Research Triangle Park, NC, USA

    Jeremey Levin & John Hohneker

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  1. Jeremey Levin
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Levin, J., Hohneker, J. Clinical Development of Eniluracil/Fluorouracil: an Oral Treatment for Patients with Solid Tumors. Invest New Drugs 18, 383–390 (2000). https://doi.org/10.1023/A:1006457617467

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