Bernhard Wörmann1,2, Carsten Bokemeyer3, Thomas Burmeister4, Claus-Henning Köhne5, Matthias Schwab6,7,8, Dirk Arnold9, Jens-Uwe Blohmer10, Markus Borner11, Sara Brucker12, Ingolf Cascorbi13, Thomas Decker14, Maike de Wit15, Andreas Dietz16, Hermann Einsele17, Wolfgang Eisterer18, Gunnar Folprecht19, Wolfgang Hilbe20, Jürgen Hoffmann21, Wolfgang Knauf22, Volker Kunzmann17, Carlo R Largiadèr23, Sylvie Lorenzen24, Diana Lüftner4, Markus Moehler25, Markus M Nöthen26, Christian Pox27, Anke Reinacher-Schick28, Anton Scharl29, Brigitte Schlegelberger30, Thomas Seufferlein31, Marianne Sinn3, Matthias Stroth32, Ingo Tamm33, Lorenz Trümper34, Martin Wilhelm35, Ewald Wöll36, Ralf-Dieter Hofheinz37. 1. Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie, Berlin, Germany, woermann@dgho.de. 2. Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany, woermann@dgho.de. 3. II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. 4. Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany. 5. Klinik für Onkologie und Hämatologie, Oldenburg, Germany. 6. Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany. 7. Departments of Clinical Pharmacology, and of Biochemistry and Pharmacy, University of Tübingen, Tübingen, Germany. 8. Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany. 9. Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Germany. 10. Klinik für Gynäkologie, Charité, Berlin, Germany. 11. Onkologisches Zentrum, Oncocare, Engeriedspital, Bern, Switzerland. 12. Department für Frauengesundheit, Universitätsklinikum Tübingen, Tübingen, Germany. 13. Institut für Experimentelle und Klinische Pharmakologie, Universitätsklinikum Kiel, Kiel, Germany. 14. Onkologische Praxis, Ravensburg, Germany. 15. Klinik für Innere Medizin, Hämatologie, Onkologie und Palliativmedizin, Vivantes Klinikum Neukölln, Berlin, Germany. 16. Klinik und Poliklinik für Hals-Nasen-Ohren-Heilkunde, Universitätsklinikum Leipzig, Leipzig, Germany. 17. Medizinische Klinik II, Universitätsklinikum Würzburg, Würzburg, Germany. 18. Abteilung für Innere Medizin und Onkologie, Klinikum Klagenfurt, Klagenfurt am Wörthersee, Austria. 19. Medizinische Klinik I, Universitätsklinikum Dresden, Dresden, Germany. 20. Medizinische Abteilung am Wilhelminenspital, Wien, Austria. 21. Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Heidelberg, Heidelberg, Germany. 22. Centrum für Hämatologie und Onkologie, Bethanien-Krankenhaus, Frankfurt/Main, Germany. 23. Universitätsinstitut für Klinische Chemie, Inselspital Bern, Bern, Switzerland. 24. Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar, München, Germany. 25. I. Medizinische Klinik, Universitätsmedizin Mainz, Mainz, Germany. 26. Institut für Humangenetik, Universitätsklinikum Bonn, Bonn, Germany. 27. Medizinische Klinik, Krankenhaus St. Joseph-Stift, Bremen, Germany. 28. Hämatologie, Onkologie und Palliativmedizin, Katholisches Klinikum, Ruhr-Universität, Bochum, Germany. 29. Frauenkliniken Amberg-Tirschenreuth-Weiden, Amberg, Germany. 30. Institut für Humangenetik, Medizinische Hochschule Hannover, Hannover, Germany. 31. Klinik für Innere Medizin I, Universitätsklinikum Ulm, Ulm, Germany. 32. Klinik für Frauenheilkunde, Berlin, Germany. 33. Onkologische Schwerpunktpraxis Kurfürstendamm, Berlin, Germany. 34. Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin Göttingen, Göttingen, Germany. 35. Klinik für Innere Medizin 5, Klinikum Nürnberg, Paracelsus Medical University, Nuremberg, Germany. 36. Klinik für Innere Medizin, Klinikum St. Vinzenz, Zams, Austria. 37. Interdisziplinäres Tumorzentrum, Universitätsmedizin Mannheim, Mannheim, Germany.
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.
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.
Authors: Ursina B M Begré; Markus Jörger; Stefan Aebi; Ursula Amstutz; Carlo R Largiadèr Journal: Front Pharmacol Date: 2022-05-18 Impact factor: 5.988
Authors: P García-Alfonso; M Saiz-Rodríguez; R Mondéjar; J Salazar; D Páez; A M Borobia; M J Safont; I García-García; R Colomer; X García-González; M J Herrero; L A López-Fernández; F Abad-Santos Journal: Clin Transl Oncol Date: 2021-11-13 Impact factor: 3.405