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

项目总结/摘要 多药（PP），或同时使用多种药物，影响高达80%的老年人， 癌它与使用潜在不适当的药物（PIM）有关，这些药物的风险更大， 而不是对老年人有益。在老年癌症患者中，PP/PIM在一些研究中与以下因素相关： 不良结局，包括对癌症治疗的依从性和耐受性差， 功能然而，这些数据一直不一致，迄今为止的研究已经检查了具体的 人群（如参加临床试验的疾病特异性亚组）可能不代表 老年癌症患者的一般人群。该提案提出了为期2年的研究和职业生涯 发展计划的重点是检查一个队列（n=370）的老年人与晚期癌症接受 在社区肿瘤诊所进行化疗。这是老年组对照组的二次分析。 接受化疗或类似药物治疗的70岁及以上患者的评估干预 晚期癌症（“GAP”）：降低老年人毒性研究（URCC 13059，主要研究者是 主要导师Mohile博士），描述了PP/PIM的患病率和模式以及与 PP/PIM与不良结局的关系，包括化疗的相对剂量强度（RDI，接受与接受化疗的比率）。 标准剂量的化疗）、化疗毒性和功能轨迹。候选人艾丽卡博士 Ramsdale是罗切斯特大学的医学助理教授， 肿瘤学和老年医学。这项建议建立在她之前对老年人PP/PIM的系统性综述的基础上。 癌症患者，显示文献中可用的有限数据，她的工作表明， PP/PIM与老年晚期癌症患者在开始治疗前的功能障碍相关 化疗拟议研究的目的是：1/检验PP/PIM比率将更高的假设 比大多数先前的研究报告，非处方药将包括大部分的PIM 检测到; 2/在老年人中检查PP/PIM与以下不良结局的相关性， 癌症开始化疗：3个月时的化疗耐受性（RDI，3-5级化疗毒性）， 和功能下降超过3个月。一个探索性的目标也将比较回归和 其他用于建模和预测影响化疗毒性的因素的监督分类方法， 包括PP/PIM和功能状态。该提案描述了全面的指导和培训 计划在多药、定量分析和数据方面发展补充技能和知识 科学在她的主要导师Supriya Mohile博士的指导下，共同导师冬青霍姆斯博士和博士。 Martin Zand和顾问伊娃Culakova博士，她将以长期目标来提高她在这些领域的技能 成为一名独立的老年肿瘤学研究人员，实施和测试多层次的干预措施， 解决老年癌症患者的多种药物治疗问题。

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.