Correlation of cytidine deaminase polymorphisms and activity with clinical outcome in gemcitabine-/platinum-treated advanced non-small-cell lung cancer patients

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Abstract

Background: The aim of this study was to evaluate whether cytidine deaminase (CDA) polymorphisms 79A>C and 435C>T and/or CDA enzymatic activity influenced clinical outcome in 126 advanced non-small-cell lung cancer patients treated with gemcitabine-platinum-regimens. Patients and methods: CDA polymorphisms and activity were analysed by PCR and high-performance liquid chromatography, respectively. Univariate and multivariate analyses compared biological/clinical parameters with response, clinical benefit, time to progression (TtP) and overall survival (OS) using Pearson's χ2 test, log-rank test and Cox proportional hazards model. Results: Patients with CDA A79A/A79C genotypes had significantly longer TtP (6.0 versus 3.0 months; P = 0.001) and OS (11.0 versus 5.0 months; P = 0.001) than patients with C79C genotype. Patients harbouring CDA C435C/C435T genotypes also had a longer OS (P = 0.025), but no correlations were observed with TtP. Conversely, patients with low-CDA activity had a significantly higher response rate (37.7% versus 13.8%; P = 0.006), clinical benefit (91.8% versus 51.7%; P < 0.001), as well as longer TtP (8.0 versus 3.0 months; P < 0.001) and OS (19.0 versus 6.0 months; P < 0.001). Furthermore, enzymatic activity emerged as an independent predictor for death/progression risk at multivariate analysis. Conclusions: CDA enzymatic activity appears to be the strongest candidate biomarker of activity and efficacy of platinum-gemcitabine-based chemotherapy and should be validated in a prospective study. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

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Tibaldi, C., Giovannetti, E., Tiseo, M., Leon, L. G., D’incecco, A., Loosekoot, N., … Peters, G. J. (2012). Correlation of cytidine deaminase polymorphisms and activity with clinical outcome in gemcitabine-/platinum-treated advanced non-small-cell lung cancer patients. Annals of Oncology, 23(3), 670–677. https://doi.org/10.1093/annonc/mdr280

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