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Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing chemotherapy in colorectal cancer

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An Erratum to this article was published on 28 June 2013

Abstract

Purpose

Oxaliplatin or irinotecan is usually administered jointly with fluoropyrimidines in colorectal cancer patients treated with chemotherapy. Both drugs have different toxicity patterns. Biomarkers for predicting high-risk severe adverse reactions can help select the best treatment.

Methods

A retrospective analysis of 106 colorectal cancer patients receiving an oxaliplatin-based treatment and 56 receiving an irinotecan-based treatment was performed. One copy number variant (GSTT1) and nine polymorphisms in irinotecan and oxaliplatin metabolism, transport or DNA repair genes (ABCB1, UGT1A1, XRCC1, ERCC1, ERCC2, GSTP1) were genotyped by SNaPshot, polymerase chain reactions’ length fragments, or copy number assays.

Results

In irinotecan-treated patients, C allele of ABCB1 C1236T SNP was associated with a lower risk of asthenia (OR = 0.043; 96 % CI = 0.004–0.444; P = 0.008) and C allele of ABCB1 C3435T SNP was associated with a lower risk of diarrhea (OR = 0.162; 95 % CI = 0.031–0.844; P = 0.031); and individuals with two copies of GSTT1 gene had a lower risk for asthenia (OR = 0.074; 95 % CI = 0.009–0.617; P = 0.016). In oxaliplatin-treated patients, carriers of two C variants of Asn118Asn ERCC1 SNP had a lower risk for neutropenia (OR = 0.203; 95 % CI = 0.060–0.683; P = 0.01).

Conclusions

These biomarkers could help oncologists select the best treatment by reducing toxicity associated with irinotecan or oxaliplatin in colorectal cancer patients, thus increasing their quality of life.

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Acknowledgments

Work was supported by a grant from Insituto de Salud Carlos III (PI12/00056) and “Programa Miguel Servet CP/0267” to Luis A. López-Fernández. The authors would like to thank the Sequencing Facility from “Instituto de Investigación Sanitaria Gregorio Marañón” for technical help, and Braden Lang for editorial assistance.

Conflict of interest

The authors of this manuscript declare that they have no competing interests.

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Authors and Affiliations

  1. Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Doctor Esquerdo 46, 28007, Madrid, Spain

    Lucía Cortejoso, María I. García, Eva González-Haba, Fernando Escolar, María Sanjurjo & Luis A. López-Fernández

  2. Servicio de Oncología Médica, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Doctor Esquerdo 46, 28007, Madrid, Spain

    Pilar García-Alfonso

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Cortejoso, L., García, M.I., García-Alfonso, P. et al. Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing chemotherapy in colorectal cancer. Cancer Chemother Pharmacol 71, 1463–1472 (2013). https://doi.org/10.1007/s00280-013-2145-6

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