8 research outputs found
Utilisation of cement-asbestos wastes by thermal treatment and the potential possibility use of obtained product for the clinker bricks manufacture
PadrĂ”es de utilização de atendimento mĂ©dico-ambulatorial no Brasil entre usuĂĄrios do Sistema Ănico de SaĂșde, da saĂșde suplementar e de serviços privados
Application of liquid chromatography-mass spectrometry to monitoring plasma cyclophosphamide levels in phase I trial cancer patients*
Environmental and biological monitoring of antineoplastic drugs in four workplaces in a Swedish hospital
Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients
Background: Dihydropyrimidine dehydrogenase (DPD) catabolizes approximately 85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated
DPD activity. DPYD variants analysis may help for defining individual patients' risk of fluoropyrimidine-related severe toxicity. Methods: The TOSCA Italian randomized trial enrolled colon cancer patients for 3 or 6 months of
either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, ten 49 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, rs75017182 C>G), were retrospectively tested for associations with > grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg's False
Discovery Rate (FDR) procedure was used.
55 Results: FAEs occurred in 194/508 assessable patients (38.2%). In the association analysis, FAEs
56 occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT
57 analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001),
58 *2A rs3918290 A allele carriers (FDR <0.0001), rs2297595 GG genotype carriers (FDR=0.0014).
59 Neutropenia was the commonest FAEs (28.5%). *6 rs1801160 (FDR <.0001), and *2A
60 rs3918290 (FDR =0.0004) variant alleles were significantly associated with time to neutropenia.
61 Conclusions: This study adds evidence on the role of DPYD pharmacogenetics for safety of
62 patients undergoing fluoropyrimidine-based chemotherapy