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Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper.

Oncology research and treatment

Authors: 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

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.

© 2020 S. Karger AG, Basel.

PMID: 33099551

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