Identification of baseline parameters associated with the inter-individual variability in cytidine deaminase serum activity, a key enzyme in the metabolism of pyrimidine analogue

Background

Cytidine deaminase (CDA) catabolizes gemcitabine and cytosine arabinoside and its serum activity (CDA-A) has been associated with efficacy and toxicity of both treatments. CDA is mainly produced by hepatocytes and neutrophils. Our objective was to identify pretreatment patients (pts) characteristics that may contribute to the large inter-individual variability in CDA-A.

Methods

From December 2014 to November 2015, all consecutive pts were prospectively included into this single-center study. CDA-A in serum was assayed using a standardized spectrophotometric method. Biological, clinical characteristics and 5 common single nucleotide polymorphisms in the CDA gene (-451g > a, -92a > g, -33delc, 79a > c, 435t > c) were analyzed according to pretreatment CDA-A. Written consent was obtained from all patients. Univariate and multivariate statistical analysis were performed on log-transformed CDA-A with significance level of 0.05.

Results

275 pts (male: 61%) were analyzed. Median age was 66.2 years. Main primary tumor locations were lung (19%), prostate (11%) and urinary tract (10%). Median CDA-A was 4.08 u/mg protein (range 1.53-15.49). The inter-individual variability in CDA-A was large (43%). 49 pts (18%) had high CDA-A (> 6 U/mg). In univariate analysis, high CDA-A was associated with absolute neutrophil count (ANC) (p 

Conclusions

Our results show for the first time an association between the pretherapeutic number of neutrophils and CDA activity, suggesting a CDA release from neutrophils. However, it explains only a small part of inter-individual variability in CDA-A. Therefore, CDA-A assessment in serum remains of interest to identify pts with high risk of toxicity or low efficacy under pyrimidine analogues.

Clinical trial identification

Legal entity responsible for the study

Paris Descartes University, Cochin - Port Royal Hospital, AP-HP

Funding

None

Disclosure

F. Goldwasser: Honoraria: Fresenius Kabi, Boehringer Ingelheim, Bayer, Pfizer Consulting or Advisory Role: Fresenius Kabi, Bayer. Travel, accomodation: Bayer, Novartis, AsrtaZeneca, Roche Glycart. All other authors have declared no conflicts of interest.