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 o...