Department of Cancer Pharmacology & Pharmacogenomics, Atrium Health Levine Cancer Institute, 1021 Morehead Medical Drive, Charlotte, NC, 28204, USA.
Department of Biostatistics, Atrium Health Levine Cancer Institute, Charlotte, NC, USA.
Support Care Cancer. 2021 Oct;29(10):5927-5934. doi: 10.1007/s00520-021-06170-4. Epub 2021 Mar 24.
We estimated the prevalence of potentially actionable pharmacogenetic (PGx) variants related to symptom control medications (SCMs) based on institutional prescribing patterns and correlated presenting symptoms with SCM prescribing.
This was a retrospective study of adult ambulatory cancer patients undergoing electronic distress screening (EDS) within 90 days of intake to the cancer hospital. We estimated the proportion prescribed SCM(s) with PGx evidence within 90 days of intake. Those with potentially actionable variants were estimated using population frequency data from 1000 genomes. The expected number at risk of altered drug response was estimated. The associations between symptom scores and SCM(s) were estimated with logistic regression and threshold analyses performed with receiver operating characteristic (ROC) curves.
Of 6985 patients, 3222 (46%) received ≥ one SCM. Of these, 2760 (86%) received SCM(s) with PGx evidence for CYP2B6, CYP2C19, CYP2D6, or SLC6A4; 2719 (84%) received a drug metabolized by CYP2D6, most commonly hydrocodone (40.4%), ondansetron (35.6%), oxycodone (24.2%), and/or tramadol (7.1%). Based on this, about one quarter were expected to have altered metabolism and/or drug response. One third were prescribed two or more SCMs with PGx evidence. About half reported at least one severe symptom, which significantly correlated with SCM prescribing (p < 0.001). Threshold scores were identified that highly correlated with SCM prescribing for anxiety, depression, nausea, neuropathy, pain, and sleep.
About half presented with significant symptom burden, which highly correlated with SCM prescribing. Most received SCMs with PGx evidence. Preemptive PGx testing for these variants should be evaluated in prospective trials to evaluate the impact on symptom control.
根据机构处方模式，估算与症状控制药物（SCM）相关的潜在可操作药物遗传学（PGx）变体的流行率，并将表现症状与 SCM 处方相关联。
这是一项回顾性研究，纳入了在癌症医院就诊后 90 天内接受电子不适筛查（EDS）的成年门诊癌症患者。我们估算了在摄入后 90 天内开具 SCM 的患者中具有 PGx 证据的比例。使用来自 1000 基因组的人群频率数据估算具有潜在可操作变体的患者。估计易发生药物反应改变的风险人数。使用逻辑回归估计症状评分与 SCM 的关联，并通过接受者操作特征（ROC）曲线进行阈值分析。
在 6985 例患者中，3222 例（46%）接受了≥1 种 SCM。其中，2760 例（86%）接受了 CYP2B6、CYP2C19、CYP2D6 或 SLC6A4 的 PGx 证据的 SCM；2719 例（84%）接受了 CYP2D6 代谢的药物，最常见的是氢可酮（40.4%）、昂丹司琼（35.6%）、羟考酮（24.2%）和/或曲马多（7.1%）。基于此，大约四分之一的患者预计会出现代谢和/或药物反应改变。三分之一的患者开具了两种或更多具有 PGx 证据的 SCM。大约一半的患者报告至少有一种严重症状，这与 SCM 处方显著相关（p<0.001）。确定了与焦虑、抑郁、恶心、神经病变、疼痛和睡眠的 SCM 处方高度相关的阈值评分。
大约一半的患者出现了严重的症状负担，这与 SCM 处方高度相关。大多数患者接受了具有 PGx 证据的 SCM。应在前瞻性试验中评估针对这些变体的预测性 PGx 测试，以评估其对症状控制的影响。
