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. Biondi & 9 others A. Bramati, D. Turci, S. Lazzarelli, C. Verusio, F. Bergamo, A. Sobrero, L. Frontini, M. Menghi, M. Magnani

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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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Dihydrouracil Dehydrogenase (NADP)
Pharmacogenetics
Colonic Neoplasms
Alleles
Adjuvant Chemotherapy

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Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients. / Ruzzo, A.; Graziano, F.; Galli, F.; Rulli, E.; Lonardi, S.; Ronzoni, M.; Massidda, B.; Zagonel, V.; Pella, N.; Mucciarini, C.; Labianca, R.; Ionta, M.T.; Bagaloni, I.; Veltri, E.; Sozzi, P.; Barni, S.; Ricci, V.; Foltran, L.; Nicolini, M.; Biondi, E.; Bramati, A.; Turci, D.; Lazzarelli, S.; Verusio, C.; Bergamo, F.; Sobrero, A.; Frontini, L.; Menghi, M.; Magnani, M.

In: British Journal of Cancer, Vol. 117, No. 9, 2017, p. 1269-1277.

Research output: Contribution to journalArticle

Ruzzo, A, Graziano, F, Galli, F, Rulli, E, Lonardi, S, Ronzoni, M, Massidda, B, Zagonel, V, Pella, N, Mucciarini, C, Labianca, R, Ionta, MT, Bagaloni, I, Veltri, E, Sozzi, P, Barni, S, Ricci, V, Foltran, L, Nicolini, M, Biondi, E, Bramati, A, Turci, D, Lazzarelli, S, Verusio, C, Bergamo, F, Sobrero, A, Frontini, L, Menghi, M & Magnani, M 2017, 'Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients', British Journal of Cancer, vol. 117, no. 9, pp. 1269-1277. https://doi.org/10.1038/bjc.2017.289
Ruzzo, A. ; Graziano, F. ; Galli, F. ; Rulli, E. ; Lonardi, S. ; Ronzoni, M. ; Massidda, B. ; Zagonel, V. ; Pella, N. ; Mucciarini, C. ; Labianca, R. ; Ionta, M.T. ; Bagaloni, I. ; Veltri, E. ; Sozzi, P. ; Barni, S. ; Ricci, V. ; Foltran, L. ; Nicolini, M. ; Biondi, E. ; Bramati, A. ; Turci, D. ; Lazzarelli, S. ; Verusio, C. ; Bergamo, F. ; Sobrero, A. ; Frontini, L. ; Menghi, M. ; Magnani, M. / Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients. In: British Journal of Cancer. 2017 ; Vol. 117, No. 9. pp. 1269-1277.
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title = "Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients",
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",
author = "A. Ruzzo and F. Graziano and F. Galli and E. Rulli and S. Lonardi and M. Ronzoni and B. Massidda and V. Zagonel and N. Pella and C. Mucciarini and R. Labianca and M.T. Ionta and I. Bagaloni and E. Veltri and P. Sozzi and S. Barni and V. Ricci and L. Foltran and M. Nicolini and E. Biondi and A. Bramati and D. Turci and S. Lazzarelli and C. Verusio and F. Bergamo and A. Sobrero and L. Frontini and M. Menghi and M. Magnani",
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T1 - Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients

AU - Ruzzo, A.

AU - Graziano, F.

AU - Galli, F.

AU - Rulli, E.

AU - Lonardi, S.

AU - Ronzoni, M.

AU - Massidda, B.

AU - Zagonel, V.

AU - Pella, N.

AU - Mucciarini, C.

AU - Labianca, R.

AU - Ionta, M.T.

AU - Bagaloni, I.

AU - Veltri, E.

AU - Sozzi, P.

AU - Barni, S.

AU - Ricci, V.

AU - Foltran, L.

AU - Nicolini, M.

AU - Biondi, E.

AU - Bramati, A.

AU - Turci, D.

AU - Lazzarelli, S.

AU - Verusio, C.

AU - Bergamo, F.

AU - Sobrero, A.

AU - Frontini, L.

AU - Menghi, M.

AU - Magnani, M.

N1 - Export Date: 13 February 2018

PY - 2017

Y1 - 2017

N2 - 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

AB - 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

U2 - 10.1038/bjc.2017.289

DO - 10.1038/bjc.2017.289

M3 - Article

VL - 117

SP - 1269

EP - 1277

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 9

ER -