Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients

A. Ruzzo, F. Graziano, F. Galli, E. Rulli, S. Lonardi, M. Ronzoni, B. Massidda, V. Zagonel, N. Pella, C. Mucciarini, R. Labianca, M.T. Ionta, I. Bagaloni, E. Veltri, P. Sozzi, S. Barni, V. Ricci, L. Foltran, M. Nicolini, E. BiondiA. Bramati, D. Turci, S. Lazzarelli, C. Verusio, F. Bergamo, A. Sobrero, L. Frontini, M. Menghi, M. Magnani

Research output: Contribution to journalArticlepeer-review

Abstract

METHODS: The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 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, and 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. RESULTS: FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR
Original languageEnglish
Pages (from-to)1269-1277
Number of pages9
JournalBritish Journal of Cancer
Volume117
Issue number9
DOIs
Publication statusPublished - 2017

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