评估接受胃肠道癌症治疗的患者的化疗毒性,并将 5-氟尿嘧啶的治疗监测作为临床支持工具。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Lucas Silva de Baco, Laura Cé da Silva, Luis Carlos Moreira Antunes, Marina Venzon Antunes, Rafael Linden, Mauber Eduardo Schultz Moreira, Ricardo Bolsson Radins, Sarayane Araújo Brandão Maranhão, Sylvio Elvis da Silva Barbosa, Lucimara Volpato, Lauren Razzera Stefanon, Natália Brucker
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引用次数: 0

摘要

背景:5-氟尿嘧啶(5-FU)是治疗胃肠道癌症的重要药物,但有些患者会出现严重的毒性。这种毒性与暴露有关,与由 DPYD 基因解码的二氢嘧啶脱氢酶(DPD)有关。本研究旨在评估与 5-FU 血浆水平、DPYD 基因分型和 DPD 表型相关的可能毒性:方法:本研究纳入了 47 例接受 5-FU 治疗的胃肠道癌症患者。采用 UPLC-MS/MS 分析了 5-FU 血浆水平和 DPD 表型。还对 DPYD 基因分型进行了评估。采用不良事件通用术语标准(CTCAE)对毒性进行分类:在血液学毒性方面,27.65%的患者出现中性粒细胞减少,78.72%的患者出现贫血,29.78%的患者出现血小板减少。我们对三个治疗周期的血浆中 5-FU 的曲线下面积(AUC)进行了评估,观察到在初始周期,48.93% 的患者暴露不足,10.63% 的患者暴露过度,共有 59.56% 的患者超出了治疗范围。在 DPYD 基因分型中,97.87% 的患者基因型为野生型,2.12% 的患者基因型为 c.1236G>A 突变(E412E,rs56038477)。共有 82.97% 的患者表现出与正常 DPD 活性相符的表型:这些发现表明,在巴西人群中对 DPYD 基因分型和 DPD 表型的评估仍需进一步研究。此外,对 5-FU 的血浆 AUC 进行分析有助于临床常规工作,是一项非常有用的工具,尤其是在识别超出治疗范围的患者,从而指导更多的个体化剂量,甚至干预与过度暴露相关的可能毒性反应方面。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of chemotherapy toxicities in patients receiving treatment for gastrointestinal cancers and therapeutic monitoring of 5-fluorouracil as a clinical support tool

Background

5-Fluorouracil (5-FU) is essential in treating gastrointestinal cancers, but some patients show severe toxicity. The toxicity is exposure-related, which is linked to the enzyme dihydropyrimidine dehydrogenase (DPD) decoded by the DPYD gene. This study aimed to evaluate the possible toxicity related to 5-FU plasma levels, DPYD genotyping, and DPD phenotyping.

Methods

Forty-seven gastrointestinal cancer patients receiving 5-FU were included in this study. 5-FU plasma levels and DPD phenotyping were analyzed by UPLC-MS/MS. DPYD genotyping was also assessed. The Common Terminology Criteria for Adverse Events (CTCAE) was used to classify the toxicity.

Results

For hematological toxicity, 27.65% showed neutropenia, 78.72% anemia, and 29.78% thrombocytopenia. The area under the curve (AUC) of 5-FU calculated from the plasma was evaluated for three treatment cycles, and we observed that at the initial cycle, 48.93% were underexposed and 10.63% were overexposed, with a total of 59.56% of patients outside the therapeutic range. In the DPYD genotyping, 97.87% of patients had a wild-type genotype, and 2.12% had c.1236G>A mutation (E412E, rs56038477). A total of 82.97% of patients showed a phenotype compatible with normal DPD activity.

Conclusion

These findings suggest that the evaluation of DPYD genotyping and DPD phenotyping in the Brazilian population still requires further study. Moreover, the analysis of the plasma AUC of 5-FU could contribute to clinical routine, being a very useful tool, especially for identifying patients outside the therapeutic range and thus guiding more individualized doses, or even in the intervention of possible toxicities related to overexposure.

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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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