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

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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.

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Data availability

The data used in this research will be made available upon reasonable request.

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Acknowledgements

The authors wish to thank the support of the Vice-Chancellor for Research, Shiraz University of Medical Sciences (Grant number: 97-01-12-18150 [15147]). We are also very grateful for the assistance of Sakineh Dehghani and Zahra Mohebbinia for the collection of blood samples.

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Authors and Affiliations

  1. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Alireza Abbaspour, Mahtab Setayesh, Marjan Tavakkoli, Fatemeh Moosavi & Omidreza Firuzi

  2. Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Alireza Abbaspour & Mahtab Setayesh

  3. Department of Hematology and Medical Oncology, Shiraz University of Medical Sciences, Shiraz, Iran

    Mehdi Dehghani & Mani Ramzi

  4. Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mehdi Dehghani & Mani Ramzi

  5. Department of Internal Medicine, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran

    Hossein Ali Rostamipour

  6. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Marziyeh Ghorbani

  7. Department of Radio-Oncology, Shiraz University of Medical Sciences, Shiraz, Iran

    Shapour Omidvari

  8. Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Shapour Omidvari

Authors
  1. Alireza Abbaspour
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  2. Mehdi Dehghani
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Correspondence to Omidreza Firuzi.

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Abbaspour, A., Dehghani, M., Setayesh, M. et al. Cytidine deaminase enzyme activity is a predictive biomarker in gemcitabine-treated cancer patients. Cancer Chemother Pharmacol 92, 475–483 (2023). https://doi.org/10.1007/s00280-023-04579-8

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