Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, Florida, USA.
Department of Clinical Pharmacy, University of Southern California, Los Angeles, California, USA.
Pharmacotherapy. 2023 Dec;43(12):1286-1296. doi: 10.1002/phar.2875. Epub 2023 Sep 21.
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.
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.
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.
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.
CYP2D6 酶代谢常用于治疗癌症相关疼痛的阿片类药物，而 CYP2D6 多态性可能导致阿片类药物反应的变异性。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。
来自两个癌症中心的成年患者前瞻性地纳入了一项混合实施-有效性临床试验，并随机分为 CYP2D6 基因指导的阿片类药物选择、临床建议或常规护理。评估了实施指标，包括提供者的反应、与建议一致的药物改变以及基线和最多 8 周时患者报告的疼痛和症状评分。
研究中大多数（87/114，76%）被邀请的患者同意参与。在 85 名随机分组的患者中，71%的患者在基线时开了羟考酮。收到 CYP2D6 测试结果的中位数（范围）时间为 10（3-37）天；24%的患者在临床记录中记录了医生对基因分型结果的承认。在有 CYP2D6 基因指导治疗建议的患者中（n=11），18%的患者的治疗改变与建议一致。在完成基线和随访问卷的患者中（n=48），常规护理组（n=26）和基因指导组（n=22）之间的平均综合疼痛评分变化（-1.01±2.1 与-0.41±2.5；p=0.19）或最后一次随访时症状严重程度（3.96±2.18 与 3.47±1.78；p=0.63）均无差异。
我们的研究表明，癌症疼痛患者对作为临床试验一部分的遗传检测具有很高的接受度。然而，提供者对基因指导建议的反应较低，这影响了对疼痛相关结果的评估。解决药物遗传学结果和临床建议实用性的障碍对于实施成功至关重要。
