Polypharmacy, Potentially Inappropriate Medications, and Adverse Outcomes in Older Adults with Advanced Cancer Receiving Chemotherapy

项目摘要/摘要 多药联用(PP)，或同时使用多种药物，影响高达80%的患有 癌症。它与潜在不适当药物(PIM)的使用有关，这些药物具有更大的风险 而不是让老年人受益。在患有癌症的老年人中，PP/PIM在一些研究中与 不良后果，包括对癌症治疗的坚持和耐受性差以及身体素质下降 功能正常。然而，这些数据一直不一致，到目前为止的研究已经检查了特定的 可能不具有代表性的人群(例如参加临床试验的特定疾病亚组) 患有癌症的老年人的一般人口。这份提案提出了为期两年的研究和职业生涯。 发展计划的重点是检查一组患有晚期癌症的老年人(n=370) 社区肿瘤诊所的化疗。这是对老年人控制臂的二次分析 70岁及以上接受化疗或类似药物治疗的患者的评估干预 晚期癌症(“GAP”)：减少老年人的毒性研究(URCC 13059，主要研究员是 主要导师Mohile博士)，描述了PP/PIM的患病率和模式以及 PP/PIM对不良结果的影响，包括化疗的相对剂量强度(RDI，接受治疗与治疗的比率 化疗的标准剂量)、化疗毒性和功能轨迹。候选人，埃里卡博士 拉姆斯代尔是罗切斯特大学的医学助理教授，并获得了这两项课程的董事会认证 肿瘤学和老年医学。这项建议建立在她之前对老年人PP/PIM的系统审查的基础上 癌症患者，显示了文献中有限的数据，以及她的工作证明 PP/PIM与老年晚期癌症患者发病前的功能损害有关 化疗。拟议研究的目的是：1/检验PP/PIMs比率将会更高的假设 而非处方药将占PIMs的大部分 检测到；2/检查PP/PIM与老年人的以下不良后果之间的关系 癌症开始化疗：3个月后化疗耐受性(RDI，3-5级化疗毒性)， 功能下降超过3个月。一个探索性的目标也将比较回归和 其他监督分类方法对影响化疗毒性的因素进行建模和预测， 包括PP/PIM和功能状态。该提案描述了一项全面的指导和培训 计划在综合药房、定量分析和数据方面发展互补的技能和知识 科学。在她的主要导师苏普里亚·莫希尔博士的指导下，她的共同导师霍莉·霍姆斯博士和苏普里亚·莫希尔博士。 马丁·赞德和顾问伊娃·卡拉科娃博士将以长期目标提升自己在这些领域的技能 成为一名独立的老年肿瘤学研究人员，实施和测试多层次干预措施 解决老年癌症患者的多药联用问题。

PROJECT SUMMARY/ABSTRACT Polypharmacy (PP), or the concurrent use of multiple medications, affects up to 80% of older adults with cancer. It is associated with the use of potentially inappropriate medications (PIMs), which have risk greater than benefit in older adults. In older adults with cancer, PP/PIMs have been associated in some studies with adverse outcomes, including poor adherence to and tolerance of cancer therapy and decrease in physical functioning. However, these data have been inconsistent, and studies to date have examined specific populations (such as disease-specific subgroups enrolled in clinical trials) that may not be representative of the general population of older adults with cancer. This proposal presents a 2-year research and career development plan focused on examining a cohort (n=370) of older adults with advanced cancer receiving chemotherapy in community oncology clinics. This is a secondary analysis of the control arm of the Geriatric Assessment Intervention for Patients Aged 70 and Over Receiving Chemotherapy or Similar Agents for Advanced Cancer (“GAP”): Reducing Toxicity in Older Adults study (URCC 13059, principal investigator is primary mentor Dr. Mohile), describing prevalence and patterns of PP/PIMs as well as the relationship of PP/PIMs to adverse outcomes including relative dose intensity of chemotherapy (RDI, a ratio of received to standard doses of chemotherapy), chemotherapy toxicity, and functional trajectory. The candidate, Dr. Erika Ramsdale, is an Assistant Professor of Medicine at the University of Rochester and is board-certified in both Oncology and Geriatric Medicine. This proposal builds upon her prior systematic review of PP/PIMs in older patients with cancer, showing the limited data available in the literature, and her work demonstrating that PP/PIMs are associated with functional impairments in older adults with advanced cancer prior to initiating chemotherapy. The aims of the proposed study are: 1/to test the hypotheses that PP/PIMs rates will be higher than reported in most prior studies, and over-the-counter medications will comprise the majority of PIMs detected; 2/to examine the association of PP/PIMs and the following adverse outcomes in older adults with cancer starting chemotherapy: chemotherapy tolerability at 3 months (RDI, grade 3-5 chemotherapy toxicity), and functional decline over 3 months. An exploratory aim will also compare the performance of regression and other supervised classification methods to model and predict factors influencing chemotherapy toxicity, including PP/PIMs and functional status. The proposal describes a comprehensive mentorship and training plan to develop complementary skills and knowledge in in polypharmacy, quantitative analysis, and data science. Under the guidance of her primary mentor Dr. Supriya Mohile, co-mentors Dr. Holly Holmes and Dr. Martin Zand, and advisor Dr. Eva Culakova, she will advance her skills in these areas with the long-term goal of becoming an independent geriatric oncology researcher implementing and testing multi-level interventions to address polypharmacy in older adults with cancer.