title: Severe fluoropyrimidine-related toxicity: clinical implications of DPYD analysis and UH2/U ratio evaluation.
abstract: The fluoropyrimidines are commonly used in chemotherapeutic cancer medicine, but many patients still experience severe adverse side effects from these drugs. We observed a severe toxicity in a 50-year-old woman treated with capecitabine and docetaxel for a metastatic breast cancer. Since dihydropyrimidine dehydrogenase (DPD) is the main candidate for pharmacogenetic studies on 5-FU toxicity, the entire coding sequence and exon-flanking intronic regions of the DPYD gene were sequenced in the patient. None of the previously described deleterious variants were detected. Also, the haplotype-based analysis failed to reveal DPYD variations associated with 5-FU toxicity. We also evaluated the UH2/U ratio in plasma as an index of 5-FU pharmacokinetics. The UH2/U value did not demonstrate low DPD activity in the patient. We discuss the advantages and limitations of this approach, particularly concerning the clinical applications of 5-FU pharmacogenetics in the family setting.
authors.affiliation: Laboratory of Genetics, Galliera Hospital, Genoa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Giorgio
authors.forename: C
authors.initials: C
authors.lastname: Caroti
authors.forename: F
authors.initials: F
authors.lastname: Mattioli
authors.forename: V
authors.initials: V
authors.lastname: Uliana
authors.forename: M I
authors.initials: MI
authors.lastname: Parodi
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amico
authors.forename: C
authors.initials: C
authors.lastname: Fucile
authors.forename: V
authors.initials: V
authors.lastname: Marini
authors.forename: F
authors.initials: F
authors.lastname: Forzano
authors.forename: G
authors.initials: G
authors.lastname: Cassola
authors.forename: A
authors.initials: A
authors.lastname: Martelli
authors.forename: F
authors.initials: F
authors.lastname: Faravelli
authors.forename: E
authors.initials: E
authors.lastname: Di Maria
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011743:Pyrimidines / Q000633:toxicity*; D014498:Uracil / Q000031:analogs & derivatives* / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; C007419:dihydrouracil; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP)