Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur

  • Bernhard Wörmann
  • Carsten Bokemeyer
  • Thomas Burmeister
  • Claus-Henning Köhne
  • Matthias Schwab
  • Dirk Arnold
  • Jens-Uwe Blohmer
  • Markus Borner
  • Sara Brucker
  • Ingolf Cascorbi
  • Thomas Decker
  • Maike de Wit
  • Andreas Dietz
  • Hermann Einsele
  • Wolfgang Eisterer
  • Gunnar Folprecht
  • Wolfgang Hilbe
  • Jürgen Hoffmann
  • Wolfgang Knauf
  • Volker Kunzmann
  • Carlo R Largiadèr
  • Sylvie Lorenzen
  • Diana Lüftner
  • Markus Moehler
  • Markus M Nöthen
  • Christian Pox
  • Anke Reinacher-Schick
  • Anton Scharl
  • Brigitte Schlegelberger
  • Thomas Seufferlein
  • Marianne Sinn
  • Matthias Stroth
  • Ingo Tamm
  • Lorenz Trümper
  • Martin Wilhelm
  • Ewald Wöll
  • Ralf-Dieter Hofheinz

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BACKGROUND: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%.

SUMMARY: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.

Bibliographical data

Original languageEnglish
Publication statusPublished - 23.10.2020
PubMed 33099551