CYP2D6指导的阿片类药物治疗成人癌症疼痛:一项随机实施的临床试验。

IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Pharmacotherapy Pub Date : 2023-12-01 Epub Date: 2023-09-21 DOI:10.1002/phar.2875
Scott A Mosley, Emily Cicali, Alex Del Cueto, Diane G Portman, Kristine A Donovan, Yan Gong, Taimour Langaee, Priya Gopalan, Jessica Schmit, Jason S Starr, Natalie Silver, Young D Chang, Sahana Rajasekhara, Joshua E Smith, Heloisa P Soares, Michael Clare-Salzler, Petr Starostik, Thomas J George, Howard L McLeod, Roger B Fillingim, J Kevin Hicks, Larisa H Cavallari
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引用次数: 0

摘要

简介:CYP2D6酶代谢通常用于癌症相关疼痛的阿片类药物,CYP2D6多态性可能导致阿片类反应的变异。我们评估了为癌症患者实施CYP2D6指导的阿片类药物处方的可行性,并报告了试点结果数据。方法:来自两个癌症中心的成年患者前瞻性地纳入一项混合实施有效性临床试验,并随机接受CYP2D6基因型指导的阿片类药物选择、临床推荐或常规护理。实施指标,包括提供者反应、与建议一致的药物变化,以及患者报告的基线疼痛和症状评分,最高8分 周。结果:大多数(87/114,76%)参与研究的患者同意参与。在85名随机分组的患者中,71%的患者在基线时服用了羟考酮。接受CYP2D6检测结果的中位(范围)时间为10(3-37) 天;24%的患者让医生在临床记录中承认基因型结果。在CYP2D6基因型患者中,改变治疗的建议(n = 11) ,18%的人有与建议一致的变化。在完成基线和随访问卷的患者中(n = 48),平均复合疼痛评分的变化没有差异(-1.01 ± 2.1对-0.41 ± 2.5;p = 0.19)或最后一次随访时的症状严重程度(3.96 ± 2.18对3.47 ± 1.78;p = 0.63)在常规护理臂(n = 26)和基因型引导的臂(n = 22)。结论:我们的研究表明,作为癌症疼痛患者临床试验的一部分,药物遗传学测试得到了高度接受。然而,提供者对基因型指导建议的反应很低,影响了疼痛相关结果的评估。解决药物遗传学结果和临床建议的使用障碍对实施成功至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CYP2D6-guided opioid therapy for adults with cancer pain: A randomized implementation clinical trial.

Introduction: The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer-related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6-guided opioid prescribing for patients with cancer and reported pilot outcome data.

Methods: Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation-effectiveness clinical trial and randomized to CYP2D6-genotype-guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient-reported pain and symptom scores at baseline and up to 8 weeks, were assessed.

Results: Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3-37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6-genotype-guided recommendations to change therapy (n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow-up questionnaires (n = 48), there was no difference in change in mean composite pain score (-1.01 ± 2.1 vs. -0.41 ± 2.5; p = 0.19) or symptom severity at last follow-up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm (n = 26) and genotype-guided arm (n = 22), respectively.

Conclusion: Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype-guided recommendations was low, impacting assessment of pain-related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success.

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来源期刊
Pharmacotherapy
Pharmacotherapy 医学-药学
CiteScore
7.80
自引率
2.40%
发文量
93
审稿时长
4-8 weeks
期刊介绍: Pharmacotherapy is devoted to publication of original research articles on all aspects of human pharmacology and review articles on drugs and drug therapy. The Editors and Editorial Board invite original research reports on pharmacokinetic, bioavailability, and drug interaction studies, clinical trials, investigations of specific pharmacological properties of drugs, and related topics.
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