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

被引:4
作者
Abbaspour, Alireza [1 ,2 ]
Dehghani, Mehdi [3 ,4 ]
Setayesh, Mahtab [1 ,2 ]
Tavakkoli, Marjan [1 ]
Rostamipour, Hossein Ali [5 ]
Ghorbani, Marziyeh [6 ]
Ramzi, Mani [3 ,4 ]
Omidvari, Shapour [7 ,8 ]
Moosavi, Fatemeh [1 ]
Firuzi, Omidreza [1 ]
机构
[1] Shiraz Univ Med Sci, Med & Nat Prod Chem Res Ctr, Shiraz, Iran
[2] Shiraz Univ Med Sci, Sch Med, Dept Internal Med, Shiraz, Iran
[3] Shiraz Univ Med Sci, Dept Hematol & Med Oncol, Shiraz, Iran
[4] Shiraz Univ Med Sci, Hematol Res Ctr, Pediat Hematol & Oncol, Shiraz, Iran
[5] Jahrom Univ Med Sci, Sch Med, Dept Internal Med, Jahrom, Iran
[6] Shiraz Univ Med Sci, Sch Pharm, Dept Pharmaceut Biotechnol, Shiraz, Iran
[7] Shiraz Univ Med Sci, Dept Radiooncol, Shiraz, Iran
[8] Shiraz Univ Med Sci, Breast Dis Res Ctr, Shiraz, Iran
关键词
Biomarker; Solid tumors; Nucleoside analogues; Pancreatic cancer; Cancer therapy; NUCLEOSIDE ANALOGS; POLYMORPHISMS; CDA; TOXICITY; PHARMACOGENETICS; GENOTYPE; LIFE;
D O I
10.1007/s00280-023-04579-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:475 / 483
页数:9
相关论文
共 33 条
  • [1] Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma
    Bengala, C
    Guarneri, V
    Giovannetti, E
    Lencioni, M
    Fontana, E
    Mey, V
    Fontana, A
    Boggi, U
    Del Chiaro, M
    Danesi, R
    Ricci, S
    Mosca, F
    Del Tacca, M
    Conte, PF
    [J]. BRITISH JOURNAL OF CANCER, 2005, 93 (01) : 35 - 40
  • [2] Bhaskar L., 2019, MOL MARKERS TREATMEN, P175, DOI [10.1016/B978-0-12-817661-0.00011-1, DOI 10.1016/B978-0-12-817661-0.00011-1]
  • [3] Buhagiar-Labarchede G., 2022, SCI REP-UK, V12, P1
  • [4] Pharmacogenetics and pharmacoepigenetics of gemcitabine
    Candelaria, M.
    de la Cruz-Hernandez, E.
    Perez-Cardenas, E.
    Trejo-Becerril, C.
    Gutierrez-Hernandez, O.
    Duenas-Gonzalez, A.
    [J]. MEDICAL ONCOLOGY, 2010, 27 (04) : 1133 - 1143
  • [5] Carpi FM, 2013, PHARMACOGENOMICS, V14, P769, DOI [10.2217/PGS.13.56, 10.2217/pgs.13.56]
  • [6] Nucleoside analogs: ready to enter the era of precision medicine?
    Ciccolini, Joseph
    Serdjebi, Cindy
    Hau Le Thi Thu
    Lacarelle, Bruno
    Milano, Gerard
    Fanciullino, Raphaelle
    [J]. EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2016, 12 (08) : 865 - 877
  • [7] Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective
    Ciccolini, Joseph
    Serdjebi, Cindy
    Peters, Godefridus J.
    Giovannetti, Elisa
    [J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2016, 78 (01) : 1 - 12
  • [8] Integrating pharmacogenetics into gemcitabine dosing-time for a change?
    Ciccolini, Joseph
    Mercier, Cedric
    Dahan, Laetitia
    Andre, Nicolas
    [J]. NATURE REVIEWS CLINICAL ONCOLOGY, 2011, 8 (07) : 439 - 444
  • [9] Cytidine Deaminase Residual Activity in Serum Is a Predictive Marker of Early Severe Toxicities in Adults After Gemcitabine-Based Chemotherapies
    Ciccolini, Joseph
    Dahan, Laetitia
    Andre, Nicolas
    Evrard, Alexandre
    Duluc, Muriel
    Blesius, Aurore
    Yang, Chenguang
    Giacometti, Sarah
    Brunet, Caroline
    Raynal, Caroline
    Ortiz, Adrien
    Frances, Nicolas
    Iliadis, Athanassios
    Duffaud, Florence
    Seitz, Jean-Francois
    Mercier, Cedric
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (01) : 160 - 165
  • [10] Determinants of the interindividual variability in serum cytidine deaminase activity of patients with solid tumours
    Cohen, R.
    Preta, L. H.
    Joste, V.
    Curis, E.
    Huillard, O.
    Jouinot, A.
    Narjoz, C.
    Thomas-Schoemann, A.
    Bellesoeur, A.
    Meyo, M. Tiako
    Quilichini, J.
    Desaulle, D.
    Nicolis, I.
    Cessot, A.
    Vidal, M.
    Goldwasser, F.
    Alexandre, J.
    Blanchet, B.
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2019, 85 (06) : 1227 - 1238