Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Cancer Chemother Pharmacol. 2023 Dec;92(6):475-483. doi: 10.1007/s00280-023-04579-8. Epub 2023 Sep 5.
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.
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.
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).
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.
吉西他滨是一种化疗药物，广泛用于治疗多种类型的癌症。胞苷脱氨酶（CDA）酶在吉西他滨的代谢中发挥重要作用。本研究旨在评估血清 CDA 残留活性在预测接受吉西他滨治疗的癌症患者药物疗效和毒性中的作用。
本前瞻性观察性研究纳入了 2019 年 5 月至 2022 年 1 月期间接受吉西他滨化疗的 63 例不同类型恶性肿瘤患者。在化疗开始前采集血样，并使用 Berthelot 测定法的改良方法测定血清 CDA 残留活性。对患者进行至少 12 个月至 41 个月的随访。记录总生存期，并根据国家癌症研究所常见术语标准记录与治疗相关的毒性。
Kaplan-Meier 分析显示，CDA 值低于中位数（≤8.06 U/mg 蛋白）的患者的生存期明显长于 CDA 值较高的患者（>8.06 U/mg，P<0.005）。在几个潜在相关因素中，单因素分析显示 CDA 活性与总生存期之间存在显著相关性（HR=4.219，95%CI 1.40-12.74，P=0.011）。另一方面，低 CDA 患者的贫血发生率明显高于高 CDA 个体（P<0.05）。
这些发现表明，CDA 活性可能是预测接受吉西他滨治疗的癌症患者生存和贫血发生的有前途的生物标志物。
