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.
authors.affiliation: Academic Medical Center, University of Amsterdam, Emma Children's Hospital and Department of Clinical Chemistry, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. a.b.vankuilenburg@amc.uva.nl
authors.forename: André B P
authors.initials: AB
authors.lastname: van Kuilenburg
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Klumpen
authors.forename: Anneke M
authors.initials: AM
authors.lastname: Westermann
authors.forename: Lida
authors.initials: L
authors.lastname: Zoetekouw
authors.forename: Henk
authors.initials: H
authors.lastname: Van Lenthe
authors.forename: Piet J M
authors.initials: PJ
authors.lastname: Bakker
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Richel
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects*; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000201:enzymology
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D002955:Leucovorin; D005472:Fluorouracil