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多西他赛AUC药代动力学参数与乳腺癌患者不良反应的相关性分析

Correlation analysis of pharmacokinetic parameters of docetaxel AUC and adverse reactions in breast cancer patients.

作者信息

Tang Yongzhe, Liu Yamin, Qin Shengying, Huai Cong, Zhang Jin, Ding Weijie, Fan Junwei, Wang Jie, Zhang Xiaoqing

机构信息

Department of Breast Surgery, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.

出版信息

Front Pharmacol. 2025 May 9;16:1563506. doi: 10.3389/fphar.2025.1563506. eCollection 2025.

Abstract

BACKGROUND

Docetaxel is commonly used in breast cancer chemotherapy. The previous drug dose is generally calculated based on body surface area (BSA). However, the metabolism varies greatly among different patients. Docetaxel therapeutic drug monitoring (TDM) helps monitor adverse drug reactions and explore the appropriate range of area under the curve (AUC) to ensure chemotherapy effectiveness and reduce adverse reaction occurrence.

METHODS

We conducted a real-world retrospective study and included 180 breast cancer patients, who received a chemotherapy regimen containing docetaxel. The patients' demographic and tumor data were reviewed. Adverse reaction data during chemotherapy treatment were collected through patient questionnaires and laboratory test results. Univariate logistic regression analysis was performed on 33 patient indexes, including basic information, blood toxicity, liver and kidney function, gastrointestinal reactions, and cardiotoxicity.

RESULTS

The adverse reactions of chemotherapy were matched with different docetaxel AUC results through univariate analysis. The patients between the groups were no statistically significant differences in terms of demographic and tumor data, including age, height, weight, BSA, and body mass index ( > 0.05). Univariate analysis revealed significant differences in albumin (ALB) levels ( = 0.037), creatinine (CREA) levels ( = 0.002), nausea occurrence ( = 0.008), vomiting occurrence ( = 0.013), rashes occurrence ( = 0.002), and chemotherapy-induced alopecia incidence (CIA) ( = 0.002). Based on the results of the univariate analysis, binary logistic regression analysis was further conducted to identify predictors contributing to the occurrence of chemotherapy adverse reactions. The results demonstrated that an AUC value greater than 2.5 mg h/L was significantly associated with increased risk of certain adverse reactions such as rashes, CIA, CREA, and ALB.

CONCLUSION

The docetaxel TDM provides a reliable basis for monitoring chemotherapy adverse reactions, with high AUC significantly associated with certain adverse reactions. Future studies are expected to include more patients and conduct multi-center trials to obtain a suitable AUC range for Chinese patients, which will guide the determination of clinical chemotherapy doses and reduce the occurrence of adverse reactions.

摘要

背景

多西他赛常用于乳腺癌化疗。以往的药物剂量通常根据体表面积(BSA)计算。然而,不同患者之间的代谢差异很大。多西他赛治疗药物监测(TDM)有助于监测药物不良反应,并探索曲线下面积(AUC)的合适范围,以确保化疗效果并减少不良反应的发生。

方法

我们进行了一项真实世界回顾性研究,纳入180例接受含多西他赛化疗方案的乳腺癌患者。回顾了患者的人口统计学和肿瘤数据。通过患者问卷和实验室检查结果收集化疗治疗期间的不良反应数据。对包括基本信息、血液毒性、肝肾功能、胃肠道反应和心脏毒性在内的33项患者指标进行单因素逻辑回归分析。

结果

通过单因素分析,化疗不良反应与不同的多西他赛AUC结果相匹配。两组患者在年龄、身高、体重、BSA和体重指数等人口统计学和肿瘤数据方面无统计学显著差异(>0.05)。单因素分析显示白蛋白(ALB)水平(=0.037)、肌酐(CREA)水平(=0.002)、恶心发生率(=0.008)、呕吐发生率(=0.013)、皮疹发生率(=0.002)和化疗引起的脱发发生率(CIA)(=0.002)存在显著差异。基于单因素分析结果,进一步进行二元逻辑回归分析以确定导致化疗不良反应发生的预测因素。结果表明,AUC值大于2.5mg·h/L与皮疹、CIA、CREA和ALB等某些不良反应风险增加显著相关。

结论

多西他赛TDM为监测化疗不良反应提供了可靠依据,高AUC与某些不良反应显著相关。未来的研究有望纳入更多患者并进行多中心试验,以获得适合中国患者的AUC范围,这将指导临床化疗剂量的确定并减少不良反应的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fe6/12098381/281c89f14f2d/fphar-16-1563506-g001.jpg

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