Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper
Bernhard Wörmann, Carsten Bokemeyer, Thomas Burmeister, Claus‐Henning Köhne, Matthias Schwab, Dirk Arnold, Jens‐Uwe Blohmer, Markus Borner, Sara Y. 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
Abstract
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.