TY - JOUR
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
Y1 - 2007
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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33846306765&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/17097873
U2 - https://doi.org/10.1016/j.ejca.2006.09.017
DO - https://doi.org/10.1016/j.ejca.2006.09.017
M3 - Article
C2 - 17097873
SN - 0959-8049
VL - 43
SP - 459
EP - 465
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 2
ER -