Determinants of the inter‐individual variability in serum cytidine deaminase activity of patients with solid tumors

Aims

Cytidine deaminase activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high inter‐individual variability in CDA activity. This study aimed at identifying determinants of this inter‐individual variability.

Methods

From December 2014 to November 2015, 183 patients were prospectively included. Serum CDA activity, biological and clinical characteristics as well as 5 common single nucleotide polymorphisms (SNPs) in the CDA gene (c.‐451C >T, c.‐92A>G, c.‐33_‐31delC, c.79A>C, c.435T>C) were analyzed. Associations between clinical characteristics, pharmacogenetic variants and CDA activity were univariately tested. P<0.1‐candidate variables were analyzed through a multivariate analysis. The association between CDA activity and toxicity was assessed for the 56 gemcitabine‐treated patients. Intra‐individual variability in CDA activity was explored in 6 pancreatic cancer patients treated with gemcitabine.

Results

Median CDA activity was 3.97 U/mg (range 1.53‐15.49 U/mg). A univariate analysis showed that CDA activity was statistically associated with Eastern Cooperative Oncology Group performance status, mild or severe malnutrition, inflammatory syndrome, leukocyte count, neutrophil count, albumin, C‐reactive protein and ‐c.‐33_‐31delC SNP. A multivariate analysis identified that only neutrophil count (p<0.0001) and severe malnutrition (p=0.0278) were independently associated with CDA activity. Low CDA activity (<2U/mg) was not statistically associated with severe gemcitabine‐related toxicities (p=0.16). A decrease in CDA activity was observed during the longitudinal follow‐up of 6 pancreatic cancer patients treated with gemcitabine (p=0.03).

Conclusions

These results suggest that neutrophil count and malnutrition should be considered for the interpretation of pretherapeutic CDA activity.

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