Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism of 5-fluorouracil (5-FU) and its derivatives (capecitabine and tegafur). Complete or partial deficiency of DPD activity has been demonstrated to induce severe toxicities in cancer patients treated with fluoropyrimidine therapy. We analyzed 180 individuals that were candidates for a treatment with 5-FU class drugs for the most common DPD mutation, IVS14+1G>A, and detected four heterozygous patients. We recorded the toxicities for all 180 individuals after the first two chemotherapy cycles and found that three of the four patients, although they were treated with a dose reduction in 50 % on the basis of the genetic analysis, all showed severe toxicities that resulted in hospitalization of patient and premature discontinuation of treatment. One patient with mutated DPD was not treated with chemotherapy upon the clinician's decision because of his DPD mutated genotype and the presence of microsatellite instability. Our data suggest that greater dose reductions or alternative therapies are needed for patients with DPD IVS14+1G>A mutations. © 2013 SIMI

Magnani, E., Farnetti, E., Nicoli, D., Casali, B., Savoldi, L., Focaccetti, C., et al. (2013). Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: The need for further revision of dose and schedule. INTERNAL AND EMERGENCY MEDICINE, 8(5), 417-423 [10.1007/s11739-013-0936-8].

Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: The need for further revision of dose and schedule

Albini, Adriana;
2013

Abstract

Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism of 5-fluorouracil (5-FU) and its derivatives (capecitabine and tegafur). Complete or partial deficiency of DPD activity has been demonstrated to induce severe toxicities in cancer patients treated with fluoropyrimidine therapy. We analyzed 180 individuals that were candidates for a treatment with 5-FU class drugs for the most common DPD mutation, IVS14+1G>A, and detected four heterozygous patients. We recorded the toxicities for all 180 individuals after the first two chemotherapy cycles and found that three of the four patients, although they were treated with a dose reduction in 50 % on the basis of the genetic analysis, all showed severe toxicities that resulted in hospitalization of patient and premature discontinuation of treatment. One patient with mutated DPD was not treated with chemotherapy upon the clinician's decision because of his DPD mutated genotype and the presence of microsatellite instability. Our data suggest that greater dose reductions or alternative therapies are needed for patients with DPD IVS14+1G>A mutations. © 2013 SIMI
Articolo in rivista - Articolo scientifico
Dihydropyrimidine dehydrogenase (DPD); Dose reduction; Fluoropyrimidine chemotherapy; Toxicity; Tumors; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Capecitabine; Colonic Neoplasms; Deoxycytidine; Dihydropyrimidine Dehydrogenase Deficiency; Dose-Response Relationship, Drug; Fluorouracil; Head and Neck Neoplasms; Heterozygote; Humans; Male; Mutation; Patient Selection; Polymerase Chain Reaction; Internal Medicine; Emergency Medicine
English
2013
8
5
417
423
none
Magnani, E., Farnetti, E., Nicoli, D., Casali, B., Savoldi, L., Focaccetti, C., et al. (2013). Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: The need for further revision of dose and schedule. INTERNAL AND EMERGENCY MEDICINE, 8(5), 417-423 [10.1007/s11739-013-0936-8].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/216829
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