Altered dihydropyrimidine dehydrogenase activity associated with mild toxicity in patients treated with 5-fluorouracil containing chemotherapy.
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.
van Kuilenburg
André B P
AB
Emma Children's Hospital and Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.b.vankuilenburg@amc.uva.nl
Klumpen
Heinz-Josef
HJ
Westermann
Anneke M
AM
Zoetekouw
Lida
L
Bakker
Piet J M
PJ
Guchelaar
Henk-Jan
HJ
Richel
Dick J
DJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*; D006405:Hematology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy
D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil