Timmers Lonneke, Boons Christel C L M, Mangnus Dirk, Van de Ven Peter M, Van den Berg Pieter H, Beeker Aart, Swart Eleonora L, Honeywell Richard J, Peters Godefridus J, Boven Epie, Hugtenburg Jacqueline G
Department of Clinical Pharmacology and Pharmacy, VU University Medical Center Amsterdam, Netherlands.
Department of Pharmacy, Slingeland Ziekenhuis Doetinchem, Netherlands.
Front Pharmacol. 2016 Sep 21;7:310. doi: 10.3389/fphar.2016.00310. eCollection 2016.
Capecitabine is a widely prescribed oral anticancer agent. We studied medication adherence and explored its use in daily practice from a patients' perspective. Patients ( = 92) starting capecitabine were followed up to five 3-week cycles. Adherence was assessed using a pill count, pharmacy data and dosing information from the patients' medical file. Self-reported adherence was measured using the Medication Adherence Report Scale (MARS). At baseline and during week 2 of cycles 1, 3, and 5, patients filled out questionnaires about quality of life, symptoms, attitude toward medicines and disease and use in daily practice. Simultaneously, blood samples were taken to determine the area under the curve (AUC) of 5'-deoxy-5-fluorouridine (5'-DFUR), 5-fluorouracil (5-FU), and α-fluoro-β-alanine (FBAL) by a population pharmacokinetic model. Associations between AUCs and patient-reported symptoms were tested for cycles 3 and 5. Most patients (84/92; 91%) had an adherence rate of ≥95 and ≤ 105%. The percentage of patients reporting any non-adherence behavior measured with MARS increased from 16% at cycle 1 to 29% at cycle 5. Symptoms were reported frequently and the dosing regimen was adjusted by the physician at least once in 62% of patients. In multivariate analysis the probability of an adjustment increased with the number of co-medication (OR 1.19, 95% CI: 1.03-1.39) and a stronger emotional response to the disease (OR 1.32, 95% CI: 1.10-1.59). The AUC of 5'-DFUR was associated with weight loss (OR 1.10, 95% CI: 1.01-1.19), AUC of FBAL with hand-foot syndrome (OR 0.90, 95% CI: 0.83-0.99), rhinorrhea (OR 1.21, 95% CI: 1.03-1.42 weight loss (OR 1.09, 95% CI: 1.00-1.20) and depression (OR 0.90, 95% CI: 0.82-0.99). Side effects were reported by one third of patients as the reason to discontinue treatment. Adherence to capecitabine was generally high. Nevertheless, adherence measured with MARS decreased over time Adherence management to support implementation of correct capecitabine use is specifically relevant in longer term treatment. In addition, it appears that adverse event management is important to support persistence. With the extending armamentarium of oral targeted anticancer agents and prolonged treatment duration, we expect the issue of medication adherence of increasing importance in oncology.
卡培他滨是一种广泛应用的口服抗癌药物。我们从患者角度研究了药物依从性，并探讨了其在日常实践中的使用情况。92名开始服用卡培他滨的患者接受了长达五个3周周期的随访。使用药片计数、药房数据以及患者病历中的给药信息评估依从性。使用药物依从性报告量表（MARS）测量自我报告的依从性。在基线以及第1、3和5周期的第2周，患者填写关于生活质量、症状、对药物和疾病的态度以及在日常实践中的使用情况的问卷。同时，采集血样，通过群体药代动力学模型测定5'-脱氧-5-氟尿苷（5'-DFUR）、5-氟尿嘧啶（5-FU）和α-氟-β-丙氨酸（FBAL）的曲线下面积（AUC）。对第3和5周期测试了AUC与患者报告症状之间的关联。大多数患者（84/92；91%）的依从率≥95%且≤105%。用MARS测量报告有任何不依从行为的患者百分比从第1周期的16%增加到第5周期的29%。症状报告频繁，62%的患者的给药方案至少被医生调整过一次。在多变量分析中，调整的可能性随着合并用药数量的增加而增加（比值比1.19，95%置信区间：1.03 - 1.39）以及对疾病的情绪反应更强（比值比1.32，95%置信区间：1.10 - 1.59）。5'-DFUR的AUC与体重减轻相关（比值比1.10，95%置信区间：1.01 - 1.19），FBAL的AUC与手足综合征相关（比值比0.90，95%置信区间：0.83 - 0.99）、流涕（比值比1.21，95%置信区间：1.03 - 1.42）、体重减轻（比值比1.09，95%置信区间：1.00 - 1.20）和抑郁（比值比0.90，95%置信区间：0.82 - 0.99）。三分之一的患者报告副作用是停药的原因。卡培他滨的依从性总体较高。然而，用MARS测量的依从性随时间下降。支持正确使用卡培他滨的依从性管理在长期治疗中特别重要。此外，不良事件管理对于支持持续治疗似乎也很重要。随着口服靶向抗癌药物的不断增加以及治疗持续时间的延长，我们预计药物依从性问题在肿瘤学中将变得越来越重要。
Zotero 插件