Oral Chemotherapy Adherence Trajectories in Chronic Myeloid Leukemia

癌症治疗的范例正在改变，因为更多的治疗是口服给药。 form.目前推荐的慢性髓系白血病治疗方法很好地说明了这一转变 白血病（CML）。CML的5年生存率在过去20年中翻了一番（31% 这在很大程度上是由于靶向药物的发现，特别是酪氨酸 激酶抑制剂（TKI）。与大多数癌症治疗相比， 在受控环境下输注，TKI是需要每日剂量的口服药物，最有可能终身使用。 慢性粒细胞白血病患者负责管理每一剂这种救命药物 每天虽然TKI是必要的，但很难坚持;大约三分之一的CML患者 据报道，他没有坚持下去。TKI治疗的有效性通过细胞遗传学和 分子反应和完全反应的实现是长期存活的预后。 依从性与完全分子反应实现相关， 提高总体生存率。那么，为什么三分之一的CML患者不依从呢？特定于 慢性粒细胞白血病，患者可能会错过TKI由于痛苦的副作用和经济毒性。痛心 降低依从性的TKI的副作用包括疲劳、疼痛、胃肠道不适 肿胀和皮疹。由于TKI的费用（30，000美元- 138，000美元/年），同时增加保险自付额和自付额（OOP） 成本例如，医疗保险D部分登记者为TKI治疗支付的平均OOP费用为8，503美元 2016年这些高昂的药物成本加上与癌症护理相关的其他OOP成本导致了 生活方式，错过医疗预约和错过药物剂量。更充分地 为了了解依从性和对临床结局的影响，我们需要考虑患者内 和患者间药物依从性的差异。这项研究将跟踪一组120名 服用TKI 12个月的个体，用客观指标衡量依从性 （用药事件监测系统）沿着每月毒性（副作用）评估 和金融）。为了了解长期依从性的可变性，我们将使用这些数据来 使用基于模型的方法确定随时间的依从性模式（或轨迹）的子组 聚类分析然后，使用定量和定性数据，我们将研究如何 不同的毒性与不同的粘附模式有关。接下来我们将检查 TKI粘附模式对细胞遗传学和分子学缓解的影响。识别 服用TKI个体的不同依从性模式对于确定亚组很重要 不遵守的风险最高，并将支持有针对性的干预措施的设计。

The paradigm of cancer treatment is changing as more treatments are administered in oral form. This shift is well illustrated by the current recommended treatment of chronic myeloid leukemia (CML). The 5-year survival rate for CML has doubled over the past two decade (31% to 66%) in large part due to the discovery of targeted drugs, specifically tyrosine kinase inhibitors (TKIs). In contrast to most cancer treatments that are administered by an infusion in a controlled setting, TKIs are oral agents that require daily doses, most likely for life. The individual with CML is responsible for administration of every dose of this life saving drug every day. Although essential, adherence to TKIs is difficult; about a third of CML patients are reported to be nonadherent. Effectiveness of TKI therapy is measured by cytogenetic and molecular response and achievement of complete response is prognostic for long term-survival. Adherence is associate with achievement of a complete molecular response and results in improved overall survival. So why are a third of individuals with CML nonadherent? Specific to CML, patients may miss TKIs due to distress from side effects and financial toxicity. Distressing side effects from TKIs that reduce adherence include fatigue, pain, gastrointestinal upset, swelling and skin rashes. Financial toxicity occurs due to the expense of the TKIs ($30,000- $138,000/year) in combination with increasing insurance co-pays and out of pocket (OOP) costs. For instance, Medicare Part D enrollees paid a mean OOP cost for TKI therapy of $8,503 in 2016. These high drug costs plus other OOP costs related to cancer care result in changes in lifestyle, missed medical appointments and missed doses of medication. To more fully understand adherence and the effects on clinical outcomes, we need to consider the intrapatient and interpatient variability of medication adherence. This study will follow a group of 120 individuals taking TKIs for 12 months, measuring adherence with an objective measure (Medication Event Monitoring System) along with monthly assessments of toxicity (side effects and financial). To understand the variability of long term adherence, we will use these data to determine subgroups of adherence patterns (or trajectories) over time using model-based cluster analysis. Then, using both quantitative and qualitative data, we will examine how different toxicities are associated with the different adherence patterns. Next we will examine the influence of TKI adherence patterns on cytogenetic and molecular response. Identifying differential patterns of adherence in individuals taking TKIs is important for identifying subgroups at the highest risk of nonadherence and will support the design of targeted interventions.