5-氟尿嘧啶和亚叶酸治疗的患者中，二氢嘧啶脱氢酶活性增加与轻度毒性相关。

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

作者信息

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

机构信息

Academic Medical Center, University of Amsterdam, Emma Children's Hospital and Department of Clinical Chemistry, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.

出版信息

Eur J Cancer. 2007 Jan;43(2):459-65. doi: 10.1016/j.ejca.2006.09.017. Epub 2006 Nov 13.

DOI:10.1016/j.ejca.2006.09.017

PMID:17097873

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.

摘要

二氢嘧啶脱氢酶（DPD）在5-氟尿嘧啶（5FU）的代谢中起关键作用。在44例接受5FU-亚叶酸治疗的患者中，研究了外周血单核细胞（PBM）和颊黏膜细胞中DPD活性对毒性的预后意义。分别有25%和21%的患者出现III/IV级血液学毒性和III/IV级胃肠道毒性。未观察到颊黏膜细胞中的DPD活性与毒性之间存在关联。相比之下，与无中性粒细胞减少症的患者以及患有III/IV级中性粒细胞减少症的患者相比，I/II级中性粒细胞减少症患者的PBM细胞中的平均DPD活性升高（P=0.002）。DPD活性处于高正常水平的患者在用5FU-亚叶酸治疗时被证明有发生轻度毒性的风险，这表明DPD在与5FU分解代谢产物相关的毒性病因中起重要作用。