Genetic markers for toxicity of adjuvant oxaliplatin and fluoropyrimidines in the phase III TOSCA trial in high-risk colon cancer patients

Annamaria Ruzzo, Francesco Graziano, Fabio Galli, Elisa Giacomini, Irene Floriani, Francesca Galli, Eliana Rulli, Sara Lonardi, Monica Ronzoni, Bruno Massidda, Vittorina Zagonel, Nicoletta Pella, Claudia Mucciarini, Roberto Labianca, Maria Teresa Ionta, Enzo Veltri, Pietro Sozzi, Sandro Barni, Vincenzo Ricci, Luisa FoltranMario Nicolini, Edoardo Biondi, Annalisa Bramati, Daniele Turci, Silvia Lazzarelli, Claudio Verusio, Francesca Bergamo, Alberto Sobrero, Luciano Frontini, Mauro Magnani

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number6828
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - Nov 5 2014

ASJC Scopus subject areas

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    Ruzzo, A., Graziano, F., Galli, F., Giacomini, E., Floriani, I., Galli, F., Rulli, E., Lonardi, S., Ronzoni, M., Massidda, B., Zagonel, V., Pella, N., Mucciarini, C., Labianca, R., Ionta, M. T., Veltri, E., Sozzi, P., Barni, S., Ricci, V., ... Magnani, M. (2014). Genetic markers for toxicity of adjuvant oxaliplatin and fluoropyrimidines in the phase III TOSCA trial in high-risk colon cancer patients. Scientific Reports, 4, [6828]. https://doi.org/10.1038/srep06828