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晚期癌症患者的药物基因组学潜力。

Pharmacogenomic potential in advanced cancer patients.

机构信息

University of Kentucky HealthCare, Lexington, KY.

University of Kentucky College of Medicine, Lexington, KY.

出版信息

Am J Health Syst Pharm. 2019 Mar 19;76(7):415-423. doi: 10.1093/ajhp/zxy079.

DOI:10.1093/ajhp/zxy079
PMID:31361818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7936720/
Abstract

PURPOSE

The prevalence of pharmacogenetically actionable medications in advanced cancer patients whose therapy may be optimized with genotype data was determined.

METHODS

Patients enrolled in our institutional molecular tumor board observational cohort were included in this study. Collected data included demographics, type(s) of cancer, and outpatient medications. Medications were classified as "pharmacogenetically actionable" if there are Clinical Pharmacogenetics Implementation Consortium (CPIC) therapeutic recommendations for that medication based on the presence of germline variations. The prevalence of pharmacogenetically actionable medications in the study population was determined, and the frequency of opportunities for pharmacogenetic prescribing and adverse event (AE) mitigation were estimated.

RESULTS

In a cohort of 193 patients with advanced cancer, 65% of patients were taking a pharmacogenetically actionable medication. Approximately 10% of the outpatient medications taken by the study population had a pharmacogenetic association. The most common pharmacogenetically actionable medications being used were ondansetron (47%), capecitabine (10%), and sertraline (7%). Using published genetic variation frequencies and AE risk, we conservatively estimated that 7.1% of cancer patients would be eligible for genetic-based medication adjustment, and 101 AEs would be prevented in 10,000 patients genotyped.

CONCLUSION

Medications with pharmacogenetic associations are used commonly in the advanced cancer patient population. This widespread exposure supports the implementation of prospective genotyping in the treatment of these high-risk patients.

摘要

目的

确定可能通过基因型数据优化治疗的晚期癌症患者中具有遗传药理学作用的药物的流行率。

方法

本研究纳入了参加我们机构分子肿瘤委员会观察队列的患者。收集的数据包括人口统计学特征、癌症类型和门诊药物。如果根据种系变异存在针对该药物的临床药物遗传学实施联盟(CPIC)治疗建议,则将药物归类为“具有遗传药理学作用”。确定研究人群中具有遗传药理学作用的药物的流行率,并估计遗传药理学处方和减轻不良反应(AE)的机会频率。

结果

在 193 名晚期癌症患者的队列中,65%的患者正在服用具有遗传药理学作用的药物。研究人群中约有 10%的门诊药物具有遗传药理学关联。最常用的具有遗传药理学作用的药物是昂丹司琼(47%)、卡培他滨(10%)和舍曲林(7%)。根据已发表的遗传变异频率和 AE 风险,我们保守估计,7.1%的癌症患者有资格进行基于遗传的药物调整,在 10000 名接受基因分型的患者中可预防 101 例 AE。

结论

具有遗传药理学关联的药物在晚期癌症患者群体中广泛使用。这种广泛的暴露支持在这些高危患者的治疗中实施前瞻性基因分型。

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JAMA Intern Med. 2015 May;175(5):691-700. doi: 10.1001/jamainternmed.2015.0289.
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