Standard-Dose Tegafur Combined With Uracil Is Not Safe Treatment After Severe Toxicity From 5-Fluorouracil or Capecitabine
Authors: Maarten J. Deenen, Wim E. Terpstra, Annemieke Cats, Henk Boot, Jan H.M. Schellens
Journal: Annals of Internal Medicine (2010)

Letters7 December 2010Standard-Dose Tegafur Combined With Uracil Is Not Safe Treatment After Severe Toxicity From 5-Fluorouracil or CapecitabineMaarten J. Deenen, PharmD, Wim E. Terpstra, MD, PhD, Annemieke Cats, MD, PhD, Henk Boot, MD, PhD, and Jan H.M. Schellens, MD, PhDMaarten J. Deenen, PharmDFrom The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands; Onze Lieve Vrouwe Gasthuis, 1091 AC, Amsterdam, The Netherlands; and The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands., Wim E. Terpstra, MD, PhDFrom The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands; Onze Lieve Vrouwe Gasthuis, 1091 AC, Amsterdam, The Netherlands; and The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands., Annemieke Cats, MD, PhDFrom The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands; Onze Lieve Vrouwe Gasthuis, 1091 AC, Amsterdam, The Netherlands; and The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands., Henk Boot, MD, PhDFrom The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands; Onze Lieve Vrouwe Gasthuis, 1091 AC, Amsterdam, The Netherlands; and The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands., and Jan H.M. Schellens, MD, PhDFrom The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands; Onze Lieve Vrouwe Gasthuis, 1091 AC, Amsterdam, The Netherlands; and The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-11-201012070-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: The most frequently prescribed anticancer drugs are the fluoropyrimidines, which include 5-fluorouracil (5-FU). Most patients tolerate fluoropyrimidines well, but about 10% develop severe, potentially life-threatening complications. The most important cause of these complications is a deficiency of dihydropyrimidine dehydrogenase (DPD), the primary enzyme that detoxifies fluoropyrimidines. Fluoropyrimidines are often combined with a compound that inhibits DPD and creates an artificial DPD deficiency, which reduces interpatient variability in tolerance of the fluoropyrimidines and should allow uniform dosing for all patients. Most clinicians who prescribe chemotherapy believe that this practice is safe for DPD-deficient patients.Objective: To describe 4 cases in ...References1. NCI. Common Terminology Criteria for Adverse Events Version 3.0. Accessed at ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf on Accessed July 26, 2010 Google Scholar2. Mattison LK, Fourie J, Hirao Y, Koga T, Desmond RA, King JR, et al. The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity: pharmacokinetic relationship between expired 13CO2 and plasma [2-13C]dihydrouracil. Clin Cancer Res. 2006;12:549-55. [PMID: 16428499] CrossrefMedlineGoogle Scholar3. Ogura K, Nishiyama T, Takubo H, Kato A, Okuda H, Arakawa K, et al. Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine. Cancer Lett. 1998;122:107-13. [PMID: 9464498] CrossrefMedlineGoogle Scholar4. Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, et al. Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs. 1996;7:548-57. [PMID: 8862723] CrossrefMedlineGoogle Scholar5. Kim WY, Nakata B, Hirakawa K. Alternative pharmacokinetics of S-1 components, 5-fluorouracil, dihydrofluorouracil and alpha-fluoro-beta-alanine after oral administration of S-1 following total gastrectomy. Cancer Sci. 2007;98:1604-8. [PMID: 17683513] CrossrefMedlineGoogle Scholar6. UFT Summary of Product Characteristics. Accessed at www.medicines.org.uk/EMC/medicine/4399/SPC/Uftoral+Hard+Capsules on 26 July 2010. Google Scholar Author, Article, and Disclosure InformationAffiliations: From The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands; Onze Lieve Vrouwe Gasthuis, 1091 AC, Amsterdam, The Netherlands; and The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byUpfront Genotyping of DPYD * 2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost AnalysisDilemma of dihydropyrimidine dehydrogenase deficiency in colorectal cancer patients: is Uftoral ® the right answer?Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancerStandard-dose tegafur-uracil (UFT) is not a safe alternative in partial dihydropyrimidine dehydrogenase-deficient patientsTegafur-uracil (UFT) in lower doses is safe for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle 7 December 2010Volume 153, Issue 11Page: 767-768KeywordsCancer treatmentChemotherapyDiarrheaDrugsEnzymesHalf lifeNeutropeniaPhenotypesRectal cancerToxicity ePublished: 7 December 2010 Issue Published: 7 December 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. 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