Increased dihydropyrimidine dehydrogenase activity associated with mild toxicity in patients treated with 5-fluorouracil and leucovorin

André B. P. van Kuilenburg, Heinz-Josef Klumpen, Anneke M. Westermann, Lida Zoetekouw, Henk van Lenthe, Piet J. M. Bakker, Dick J. Richel, Henk-Jan Guchelaar

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the metabolism of 5FU. The prognostic significance of DPD activity in peripheral blood mononuclear (PBM) cells and buccal mucosa cells with respect to toxicity was investigated in 44 patients treated with 5FU-leucovorin. Grade III/IV haematological and grade III/IV gastrointestinal toxicity were observed in 25% and 21% of the patients, respectively. No association was observed between the DPD activity in buccal mucosa cells and toxicity. In contrast, the mean DPD activity in PBM cells proved to be increased in patients experiencing grade I/II neutropenia when compared to patients without neutropenia and those suffering from grade III/IV neutropenia (P = 0.002). Patients with a high-normal DPD activity proved to be at risk of developing mild toxicity upon treatment with 5FU-leucovorin, suggesting an important role of DPD in the aetiology of toxicity associated with catabolites of 5FU. © 2006 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)459-465
JournalEuropean Journal of Cancer
Volume43
Issue number2
DOIs
Publication statusPublished - 2007
Externally publishedYes

Cite this

van Kuilenburg, André B. P. ; Klumpen, Heinz-Josef ; Westermann, Anneke M. ; Zoetekouw, Lida ; van Lenthe, Henk ; Bakker, Piet J. M. ; Richel, Dick J. ; Guchelaar, Henk-Jan. / Increased dihydropyrimidine dehydrogenase activity associated with mild toxicity in patients treated with 5-fluorouracil and leucovorin. In: European Journal of Cancer. 2007 ; Vol. 43, No. 2. pp. 459-465.
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title = "Increased dihydropyrimidine dehydrogenase activity associated with mild toxicity in patients treated with 5-fluorouracil and leucovorin",
abstract = "Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the metabolism of 5FU. The prognostic significance of DPD activity in peripheral blood mononuclear (PBM) cells and buccal mucosa cells with respect to toxicity was investigated in 44 patients treated with 5FU-leucovorin. Grade III/IV haematological and grade III/IV gastrointestinal toxicity were observed in 25{\%} and 21{\%} of the patients, respectively. No association was observed between the DPD activity in buccal mucosa cells and toxicity. In contrast, the mean DPD activity in PBM cells proved to be increased in patients experiencing grade I/II neutropenia when compared to patients without neutropenia and those suffering from grade III/IV neutropenia (P = 0.002). Patients with a high-normal DPD activity proved to be at risk of developing mild toxicity upon treatment with 5FU-leucovorin, suggesting an important role of DPD in the aetiology of toxicity associated with catabolites of 5FU. {\circledC} 2006 Elsevier Ltd. All rights reserved.",
author = "{van Kuilenburg}, {Andr{\'e} B. P.} and Heinz-Josef Klumpen and Westermann, {Anneke M.} and Lida Zoetekouw and {van Lenthe}, Henk and Bakker, {Piet J. M.} and Richel, {Dick J.} and Henk-Jan Guchelaar",
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Increased dihydropyrimidine dehydrogenase activity associated with mild toxicity in patients treated with 5-fluorouracil and leucovorin. / van Kuilenburg, André B. P.; Klumpen, Heinz-Josef; Westermann, Anneke M.; Zoetekouw, Lida; van Lenthe, Henk; Bakker, Piet J. M.; Richel, Dick J.; Guchelaar, Henk-Jan.

In: European Journal of Cancer, Vol. 43, No. 2, 2007, p. 459-465.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Increased dihydropyrimidine dehydrogenase activity associated with mild toxicity in patients treated with 5-fluorouracil and leucovorin

AU - van Kuilenburg, André B. P.

AU - Klumpen, Heinz-Josef

AU - Westermann, Anneke M.

AU - Zoetekouw, Lida

AU - van Lenthe, Henk

AU - Bakker, Piet J. M.

AU - Richel, Dick J.

AU - Guchelaar, Henk-Jan

PY - 2007

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N2 - Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the metabolism of 5FU. The prognostic significance of DPD activity in peripheral blood mononuclear (PBM) cells and buccal mucosa cells with respect to toxicity was investigated in 44 patients treated with 5FU-leucovorin. Grade III/IV haematological and grade III/IV gastrointestinal toxicity were observed in 25% and 21% of the patients, respectively. No association was observed between the DPD activity in buccal mucosa cells and toxicity. In contrast, the mean DPD activity in PBM cells proved to be increased in patients experiencing grade I/II neutropenia when compared to patients without neutropenia and those suffering from grade III/IV neutropenia (P = 0.002). Patients with a high-normal DPD activity proved to be at risk of developing mild toxicity upon treatment with 5FU-leucovorin, suggesting an important role of DPD in the aetiology of toxicity associated with catabolites of 5FU. © 2006 Elsevier Ltd. All rights reserved.

AB - Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the metabolism of 5FU. The prognostic significance of DPD activity in peripheral blood mononuclear (PBM) cells and buccal mucosa cells with respect to toxicity was investigated in 44 patients treated with 5FU-leucovorin. Grade III/IV haematological and grade III/IV gastrointestinal toxicity were observed in 25% and 21% of the patients, respectively. No association was observed between the DPD activity in buccal mucosa cells and toxicity. In contrast, the mean DPD activity in PBM cells proved to be increased in patients experiencing grade I/II neutropenia when compared to patients without neutropenia and those suffering from grade III/IV neutropenia (P = 0.002). Patients with a high-normal DPD activity proved to be at risk of developing mild toxicity upon treatment with 5FU-leucovorin, suggesting an important role of DPD in the aetiology of toxicity associated with catabolites of 5FU. © 2006 Elsevier Ltd. All rights reserved.

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