FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical Outcome in Gemcitabine-Monotherapy Treated Patients

Cindy Serdjebi, Johan Gagnière, Jérôme Desramé, Francine Fein, Rosine Guimbaud, Eric François, Thierry André, Jean-François Seitz, Carole Montérymard, Dominique Arsene, Julien Volet, Abakar Abakar-Mahamat, Thierry Lecomte, Véronique Guerin-Meyer, Jean-Louis Legoux, Gaël Deplanque, Pierre Guillet, Joseph Ciccolini, Côme Lepage and Laetitia Dahan

PLOS ONE, 2015, vol. 10, issue 8, 1-12

Abstract: Purpose: Because cytidine deaminase (CDA) is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype) on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships. Experimental design: One hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute’s Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine. Results: Five patients out of 120 (i.e., 4.6%) were found to be CDA deficient (i.e., CDA activity

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0135907

DOI: 10.1371/journal.pone.0135907

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