Correlation of cytidine deaminase polymorphisms and activity with clinical outcome in gemcitabine-/platinum-treated advanced non-small-cell lung cancer patients
Open Access
- 7 June 2011
- journal article
- research article
- Published by Elsevier in Annals of Oncology
- Vol. 23 (3), 670-677
- https://doi.org/10.1093/annonc/mdr280
Abstract
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. 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. 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. 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.Keywords
This publication has 15 references indexed in Scilit:
- Impact of Cytidine Deaminase Polymorphisms on Toxicity After Gemcitabine: The Question Is Still OngoingJournal of Clinical Oncology, 2010
- Association of Polymorphisms inAKT1andEGFRwith Clinical Outcome and Toxicity in Non–Small Cell Lung Cancer Patients Treated with GefitinibMolecular Cancer Therapeutics, 2010
- Cytidine Deaminase Residual Activity in Serum Is a Predictive Marker of Early Severe Toxicities in Adults After Gemcitabine-Based ChemotherapiesJournal of Clinical Oncology, 2010
- American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung CancerJournal of Clinical Oncology, 2009
- Distribution of gemcitabine pathway genotypes in ethnic Asians and their association with outcome in non-small cell lung cancer patientsLung Cancer, 2009
- Pharmacogenomics of Gemcitabine in Non-Small-Cell Lung Cancer and Other Solid TumorsPharmacogenomics, 2008
- Correlation of CDA, ERCC1, and XPD Polymorphisms with Response and Survival in Gemcitabine/Cisplatin–Treated Advanced Non–Small Cell Lung Cancer PatientsClinical Cancer Research, 2008
- Pharmacokinetics of Gemcitabine in Japanese Cancer Patients: The Impact of a Cytidine Deaminase PolymorphismJournal of Clinical Oncology, 2007
- Gemcitabine Pharmacogenomics: Cytidine Deaminase and Deoxycytidylate Deaminase Gene Resequencing and Functional GenomicsClinical Cancer Research, 2006
- Structural and functional analysis of the cytidine deaminase gene in patients with acute myeloid leukaemiaBritish Journal of Haematology, 1998