• Sara García Gil, Ruth Ramos Díaz, Gloria Julia Nazco Casariego, Marta Llanos Muñoz, Maria Micaela Viña Romero, Braulio Martín Calero, Jose Antonio Pérez Pérez, and Fernando Gutiérrez Nicolás.
• Servicio de Farmacia, Complejo Hospitalario Universitario de Canarias, Tenerife, España. Electronic address: saragg1991@gmail.com.
• Med Clin (Barc). 2018 Dec 14; 151 (11): 425-430.

Background And ObjectivesEvaluate the relationship between the presence of polymorphisms in genes involved in the pharmacodynamics of irinotecan (UGT1A, SLCO1B1, ABCB1 and ABCC2) and the safety of irinotecan in the treatment of metastatic colorectal cancer (mCRC).Patients And MethodsProspective observational, single-centre study of 30 months duration, which included patients diagnosed with mCRC treated with FOLFIRI was carried out. Toxicity was evaluated in each treatment cycle according to the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 NCI. Genomic DNA was obtained with a peripheral blood sample from an extraction method based on alkaline lysis. Genetic characterisation was performed using the LigthCycler®480 platform and allele-specific HybProbe® fluorescent probes. Analysed polymorphisms were: UGT1A1*28, UGT1A1*60, UGT1A7*1,*2,*3,*4, UGT1A7*12, UGT1A9*22, SLCO1B1 (rs11045879), ABCC2 (rs717620) and ABCB1 (rs1045642).ResultsThirty-four patients were included (73.5% were male, mean age 59.9 years [27-81]) in the study. Polymorphisms rs8175347, rs17868323, rs3832043, rs11692021 and rs7577677 were associated with a higher incidence of adverse effects. Furthermore, it was observed that those patients with wild-type in UGT family genes analysed have lower rates of toxicity associated with irinotecan treatment than those with certain mutated allele (P=.010).ConclusionsThese results suggest that the presence of certain polymorphisms in the UGT1A family of genes is related to the development of toxicity during treatment with irinotecan.Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

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