Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891799194> ?p ?o ?g. }
Showing items 1 to 93 of
93
with 100 items per page.
- W2891799194 abstract "e13057 Background: Metabolic clearance of fluoropyrimidines is highly dependent on the rate-limiting enzyme dihydropyrimidine dehydrogenase (DPD). Deficiency of DPD is associated with drug accumulation and severe toxicities. The DPD gene (DPYD) is highly polymorphic; however, except the G>A mutation in the splicing consensus sequence of intron 14 (IVS14+1G>A), which is responsible of severe enzyme impairment, the association of other variants with adverse reactions is unclear. Therefore, this study was aimed at examining the prevalence of DPYD variants in patients with toxicities and in subjects with good tolerability to fluoropyrimidine-based regimens. Methods: Patients affected by colorectal, breast and head/neck cancers requiring standard treatment with 5-FU or capecitabine in combination with other cytotoxic agents (irinotecan, oxaliplatin, cyclophosphamide or methotrexate) and/or antibodies (cetuximab or bevacizumab) were enrolled: 224 suffered from grade ≥2 non-hematological and ≥3 hematological toxicities (CTCAE v. 4) and 61 control patients developed adverse events to an extent not requiring dose-delay or reduction (i.e., <2 non-hematological and <3 hematological toxicities). DNA was extracted from blood and used to screen patients for known DPD variants (IVS14+1G>A, 496A>G, 1601G>A, 1627A>G, 1896T>C, 2194G>A and 2846T>C) by automatic sequencing. The study was approved by local Ethics Committee. Results: A complex pattern of DPYD variants was identified in both cohorts; the following genotypes were detected in patients with severe toxicities vs controls: 496AG+GG: 24.1 vs 21.3%; 1601GA: 12.5 vs 1.6%; 1627AG+GG: 37.1 vs 32.8%; 1896TC+TT: 6.25 vs 8.2%; IVS14+1GA: 4.9 vs 0%; 2194GA: 25.9 vs 9.8; 2846AT: 1.3 vs 0%. Conclusions: Although there was a higher prevalence of DPYD variants in patients with severe toxicities, their presence also in subjects with good tolerability suggest that their role needs to be re-evaluated, with the exception of IVS14+1GA and 2846AT which were found only in patients with poor tolerability. This study was supported in part by a grant from AIRC to R. Danesi." @default.
- W2891799194 created "2018-09-27" @default.
- W2891799194 creator A5012034272 @default.
- W2891799194 creator A5018118709 @default.
- W2891799194 creator A5030848899 @default.
- W2891799194 creator A5047125172 @default.
- W2891799194 creator A5048141257 @default.
- W2891799194 creator A5051936901 @default.
- W2891799194 creator A5054413273 @default.
- W2891799194 creator A5064024968 @default.
- W2891799194 creator A5079339947 @default.
- W2891799194 creator A5079545847 @default.
- W2891799194 creator A5083693387 @default.
- W2891799194 date "2012-05-20" @default.
- W2891799194 modified "2023-09-24" @default.
- W2891799194 title "Results of a comprehensive pharmacogenetic analysis of dihydropyrimidine dehydrogenase in patients treated with fluoropyrimidines and patterns of polymorphisms partially related to treatment tolerability." @default.
- W2891799194 doi "https://doi.org/10.1200/jco.2012.30.15_suppl.e13057" @default.
- W2891799194 hasPublicationYear "2012" @default.
- W2891799194 type Work @default.
- W2891799194 sameAs 2891799194 @default.
- W2891799194 citedByCount "1" @default.
- W2891799194 countsByYear W28917991942016 @default.
- W2891799194 crossrefType "journal-article" @default.
- W2891799194 hasAuthorship W2891799194A5012034272 @default.
- W2891799194 hasAuthorship W2891799194A5018118709 @default.
- W2891799194 hasAuthorship W2891799194A5030848899 @default.
- W2891799194 hasAuthorship W2891799194A5047125172 @default.
- W2891799194 hasAuthorship W2891799194A5048141257 @default.
- W2891799194 hasAuthorship W2891799194A5051936901 @default.
- W2891799194 hasAuthorship W2891799194A5054413273 @default.
- W2891799194 hasAuthorship W2891799194A5064024968 @default.
- W2891799194 hasAuthorship W2891799194A5079339947 @default.
- W2891799194 hasAuthorship W2891799194A5079545847 @default.
- W2891799194 hasAuthorship W2891799194A5083693387 @default.
- W2891799194 hasConcept C104317684 @default.
- W2891799194 hasConcept C123321153 @default.
- W2891799194 hasConcept C126322002 @default.
- W2891799194 hasConcept C135763542 @default.
- W2891799194 hasConcept C143998085 @default.
- W2891799194 hasConcept C197934379 @default.
- W2891799194 hasConcept C2776694085 @default.
- W2891799194 hasConcept C2778050828 @default.
- W2891799194 hasConcept C2778375690 @default.
- W2891799194 hasConcept C2779655350 @default.
- W2891799194 hasConcept C2780456651 @default.
- W2891799194 hasConcept C54355233 @default.
- W2891799194 hasConcept C55775858 @default.
- W2891799194 hasConcept C71924100 @default.
- W2891799194 hasConcept C86803240 @default.
- W2891799194 hasConcept C98274493 @default.
- W2891799194 hasConceptScore W2891799194C104317684 @default.
- W2891799194 hasConceptScore W2891799194C123321153 @default.
- W2891799194 hasConceptScore W2891799194C126322002 @default.
- W2891799194 hasConceptScore W2891799194C135763542 @default.
- W2891799194 hasConceptScore W2891799194C143998085 @default.
- W2891799194 hasConceptScore W2891799194C197934379 @default.
- W2891799194 hasConceptScore W2891799194C2776694085 @default.
- W2891799194 hasConceptScore W2891799194C2778050828 @default.
- W2891799194 hasConceptScore W2891799194C2778375690 @default.
- W2891799194 hasConceptScore W2891799194C2779655350 @default.
- W2891799194 hasConceptScore W2891799194C2780456651 @default.
- W2891799194 hasConceptScore W2891799194C54355233 @default.
- W2891799194 hasConceptScore W2891799194C55775858 @default.
- W2891799194 hasConceptScore W2891799194C71924100 @default.
- W2891799194 hasConceptScore W2891799194C86803240 @default.
- W2891799194 hasConceptScore W2891799194C98274493 @default.
- W2891799194 hasLocation W28917991941 @default.
- W2891799194 hasOpenAccess W2891799194 @default.
- W2891799194 hasPrimaryLocation W28917991941 @default.
- W2891799194 hasRelatedWork W1817568886 @default.
- W2891799194 hasRelatedWork W1987651351 @default.
- W2891799194 hasRelatedWork W1995961103 @default.
- W2891799194 hasRelatedWork W2003256992 @default.
- W2891799194 hasRelatedWork W2047544514 @default.
- W2891799194 hasRelatedWork W2082765638 @default.
- W2891799194 hasRelatedWork W2113414095 @default.
- W2891799194 hasRelatedWork W2202917400 @default.
- W2891799194 hasRelatedWork W2244389880 @default.
- W2891799194 hasRelatedWork W2274540404 @default.
- W2891799194 hasRelatedWork W2282199381 @default.
- W2891799194 hasRelatedWork W2341089873 @default.
- W2891799194 hasRelatedWork W2403515566 @default.
- W2891799194 hasRelatedWork W2754764793 @default.
- W2891799194 hasRelatedWork W2913909635 @default.
- W2891799194 hasRelatedWork W2921761060 @default.
- W2891799194 hasRelatedWork W2955844102 @default.
- W2891799194 hasRelatedWork W3023466163 @default.
- W2891799194 hasRelatedWork W3107093853 @default.
- W2891799194 hasRelatedWork W3213973057 @default.
- W2891799194 isParatext "false" @default.
- W2891799194 isRetracted "false" @default.
- W2891799194 magId "2891799194" @default.
- W2891799194 workType "article" @default.