Abstract 5031: Distribution of single nucleotide polymorphisms related to paclitaxel and carboplatin toxicity in ovarian cancer patients

Abstract

Introduction: Standard first-line treatment for ovarian cancer consists in the combined use of taxanes and platinum, with neuropathies and neutropenia the most frequent and complex adverse drug reactions (ADRs) requiring clinical management. These adverse effects may be related to differing levels of drug transport and metabolism brought about by intrinsic genetic characteristics of the patients. Single nucleotide polymorphisms (SNPs) are now recognized as key factors in the variability of drug response. In a cohort of Chilean ovarian cancer patients we analyzed the frequencies of several SNPs previously reported to be associated with paclitaxel and carboplatin ADRs. Methods: Blood samples were obtained with informed consent from adult ovarian cancer patients (n = 120). DNA was extracted and SNPs within the ABC transporter and CYP P450 gene families were genotyped. High specificity Taqman probes were used. Results: Four SNPs associated with risk of ADR within the ABC transporter family showed genotypic frequencies ranging between 0 - 23%. Frequencies for the ADR-associated variants in the CYP P450 family were 4 - 90%. Finally, for the CYP2C8 enzyme, whose function is essential in paclitaxel metabolism, the frequencies of risk-associated SNPs ranged from 2.10% to 13.6%. Conclusions: SNPs associated with paclitaxel and carboplatin ADRs are highly prevalent in the Chilean population of ovarian cancer patients studied. The identification of these variants may help avoid severe ADRs associated with chemotherapy regimes. Funding: CORFO 13CTI21526-P6 & 13IDL2-18608 Citation Format: Miguel Cordova, Maria L. Bravo, Isidora Arriagada, Elisa Cumsille, Luis Quiñones, Erasmo Bravo, Raimundo Correa, Juan E. Leiva, Cesar Paredes, Mauricio Cuello, Carolina Ibañez, Marcelo Garrido, Gareth I. Owen. Distribution of single nucleotide polymorphisms related to paclitaxel and carboplatin toxicity in ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5031. doi:10.1158/1538-7445.AM2017-5031