Altered Dihydropyrimidine Dehydrogenase Activity Associated with Mild Toxicity in Patients Treated with 5-Fluorouracil Containing Chemotherapy |
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| Authors: | André B P van Kuilenburg Heinz-Josef Klumpen Anneke M Westermann Lida Zoetekouw Piet J M Bakker Henk-Jan Guchelaar |
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| Institution: | 1. Academic Medical Center, University of Amsterdam, Emma Children's Hospital and Department of Clinical Chemistry , Amsterdam, The Netherlands;2. Academic Medical Center, University of Amsterdam, Department of Medical Oncology , Amsterdam, The Netherlands;3. Leiden University Medical Center, Department of Clinical Pharmacy and Toxicology , Leiden, The Netherlands |
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| Abstract: | Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the metabolism of 5-fluorouracil (5FU). In patients treated with capecitabine or 5FU combined with other chemotherapeutic drugs, DPD activity in peripheral blood mononuclear cells was increased in patients experiencing grade I/II neutropenia. In contrast, decreased DPD activity proved to be associated with grade I/II dermatological toxicity, including hand-foot syndrome. Thus, patients with a low-normal or high-normal DPD activity proved to be at risk of developing mild toxicity upon treatment with 5FU-based chemotherapy, demonstrating the important role of DPD in the etiology of toxicity associated with 5FU and the catabolites of 5FU. |
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| Keywords: | Dihydropyrimidine dehydrogenase FBAL 5-fluorouracil fluoro-5 6-dihydrouracil toxicity |
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