title: Genetic markers for toxicity of adjuvant oxaliplatin and fluoropyrimidines in the phase III TOSCA trial in high-risk colon cancer patients.
abstract: We investigated 17 polymorphisms in 11 genes (TS, MTHFR, ERCC1, XRCC1, XRCC3, XPD, GSTT1, GSTP1, GSTM1, ABCC1, ABCC2) for their association with the toxicity of fluoropyrimidines and oxaliplatin in colorectal cancer patients enrolled in a prospective randomized trial of adjuvant chemotherapy. The TOSCA Italian adjuvant trial was conducted in high-risk stage II-III colorectal cancer patients treated with 6 or 3 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In the concomitant ancillary pharmacogenetic study, the primary endpoint was the association of polymorphisms with grade 3-4 CTCAE toxicity events (grade 2-4 for neurotoxicity). In 517 analyzed patients, grade ≥ 3 neutropenia and grade ≥ 2 neurotoxicity events occurred in 150 (29%) and in 132 patients (24.8%), respectively. Diarrhea grade ≥ 3 events occurred in 34 (6.5%) patients. None of the studied polymorphisms showed clinically relevant association with toxicity. Hopefully, genome-wide association studies will identify new and more promising genetic variants to be tested in future studies.
authors.affiliation: Department of Biomolecular Sciences, Università degli Studi di Urbino "Carlo Bo"
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ruzzo
authors.affiliation: Azienda Ospedaliera "Ospedali Riuniti Marche Nord", Pesaro.
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.affiliation: Laboratorio di Ricerca Clinica, Department of Medical Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano.
authors.forename: Fabio
authors.initials: F
authors.lastname: Galli
authors.affiliation: Department of Biomolecular Sciences, Università degli Studi di Urbino "Carlo Bo"
authors.forename: Elisa
authors.initials: E
authors.lastname: Giacomini
authors.affiliation: Laboratorio di Ricerca Clinica, Department of Medical Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano.
authors.forename: Irene
authors.initials: I
authors.lastname: Floriani
authors.affiliation: Laboratorio di Ricerca Clinica, Department of Medical Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano.
authors.forename: Francesca
authors.initials: F
authors.lastname: Galli
authors.affiliation: Laboratorio di Ricerca Clinica, Department of Medical Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano.
authors.forename: Eliana
authors.initials: E
authors.lastname: Rulli
authors.affiliation: IOV- IRCCS, Padova.
authors.forename: Sara
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Ospedale San Raffaele, Milano.
authors.forename: Monica
authors.initials: M
authors.lastname: Ronzoni
authors.affiliation: Azienda Ospedaliera Universitaria di Cagliari, P.O. Monserrato.
authors.forename: Bruno
authors.initials: B
authors.lastname: Massidda
authors.affiliation: IOV- IRCCS, Padova.
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.affiliation: Azienda Ospedaliera Universitaria di Udine, Udine.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pella
authors.affiliation: Ospedale "B. Ramazzini", Carpi.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mucciarini
authors.affiliation: Ospedale Papa Giovanni XXIII, Bergamo.
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.affiliation: Azienda Ospedaliera Universitaria di Cagliari, P.O. Monserrato.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ionta
authors.affiliation: Ospedale di Gaeta ASL Latina.
authors.forename: Enzo
authors.initials: E
authors.lastname: Veltri
authors.affiliation: Ospedale degli Infermi di Biella.
authors.forename: Pietro
authors.initials: P
authors.lastname: Sozzi
authors.affiliation: Ospedale "Treviglio-Caravaggio", Treviglio.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
authors.affiliation: Ospedale San Raffaele, Milano.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ricci
authors.affiliation: Azienda Ospedaliera Universitaria di Udine, Udine.
authors.forename: Luisa
authors.initials: L
authors.lastname: Foltran
authors.affiliation: Azienda Ospedaliera Ospedale "Cervesi", Cattolica.
authors.forename: Mario
authors.initials: M
authors.lastname: Nicolini
authors.affiliation: Ospedale "F, Renzetti", Lanciano.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Biondi
authors.affiliation: Azienda Ospedaliera Fatebenefratelli, Milano.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bramati
authors.affiliation: AUSL Ospedale di Ravenna.
authors.forename: Daniele
authors.initials: D
authors.lastname: Turci
authors.affiliation: Azienda Ospedaliera di Cremona.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lazzarelli
authors.affiliation: Ospedale di Saronno.
authors.forename: Claudio
authors.initials: C
authors.lastname: Verusio
authors.affiliation: IOV- IRCCS, Padova.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bergamo
authors.affiliation: Azienda Ospedaliera "Ospedale San Martino", Genova.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sobrero
authors.affiliation: Fondazione GISCAD.
authors.forename: Luciano
authors.initials: L
authors.lastname: Frontini
authors.affiliation: Department of Biomolecular Sciences, Università degli Studi di Urbino "Carlo Bo"
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D009503:Neutropenia / Q000139:chemically induced / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: C000715087:ABCC2 protein, human; D014408:Biomarkers, Tumor; D000089762:Multidrug Resistance-Associated Protein 2; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil