Cytidine deaminase enzyme activity is a predictive biomarker in gemcitabine-treated cancer patients

Cancer Chemother Pharmacol. 2023 Dec;92(6):475-483. doi: 10.1007/s00280-023-04579-8. Epub 2023 Sep 5.

Abstract

Background: Gemcitabine is a chemotherapeutic agent, widely used for the treatment of many types of cancer. Cytidine deaminase (CDA) enzyme plays an important role in the metabolism of gemcitabine. This study aimed to assess the power of serum CDA residual activity in predicting drug efficacy and toxicity in gemcitabine-treated cancer patients.

Methods: This prospective observational study enrolled 63 patients with different types of malignancies who received gemcitabine chemotherapy between May 2019 and January 2022. Blood samples were obtained before the initiation of chemotherapy and serum CDA residual activity was determined using a modification of the Berthelot assay. The patients were followed up for at least 12 months up to 41 months. Overall survival was recorded and treatment-related toxicities were documented according to National Cancer Institute Common Terminology Criteria.

Results: Kaplan-Meier analysis showed that patients with a lower than median CDA value (≤ 8.06 U/mg protein) had a significantly longer survival compared to patients with higher CDA values (> 8.06 U/mg, P ˂ 0.005). Among several potentially involved factors, a significant association between CDA activity and overall survival was observed in univariate analysis (HR = 4.219, 95% CI 1.40-12.74, P = 0.011). On the other hand, the rate of anemia was significantly higher in low-CDA patients compared to high-CDA individuals (P < 0.05).

Conclusion: These findings suggest that CDA activity could be a promising biomarker to predict survival and the occurrence of anemia in cancer patients treated with gemcitabine.

Keywords: Biomarker; Cancer therapy; Nucleoside analogues; Pancreatic cancer; Solid tumors.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia* / chemically induced
  • Biomarkers
  • Cytidine Deaminase / metabolism
  • Deoxycytidine / adverse effects
  • Gemcitabine
  • Humans
  • Neoplasms* / drug therapy

Substances

  • Gemcitabine
  • Deoxycytidine
  • Biomarkers
  • Cytidine Deaminase