Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis

Abstract

Background Polypharmacy (PP) and potentially inappropriate medications (PIM) are highly prevalent in older adults with cancer. This study systematically reviews the associations of PP and/or PIM with outcomes and, through a meta‐analysis, obtains estimates of postoperative outcomes associated with PP in this population. Materials and Methods We searched PubMed, Embase, Web of Science, and Cochrane Register of Clinical Trials using standardized terms for concepts of PP, PIM, and cancer. Eligible studies included cohort studies, cross‐sectional studies, meta‐analyses, and clinical trials which examined outcomes associated with PP and/or PIM and included older adults with cancer. A random effects model included studies in which definitions of PP were consistent to examine the association of PP with postoperative complications. Results Forty‐seven articles met the inclusion criteria. PP was defined as five or more medications in 57% of the studies. Commonly examined outcomes included chemotherapy toxicities, postoperative complications, functional decline, hospitalization, and overall survival. PP was associated with chemotherapy toxicities (4/9 studies), falls (3/3 studies), functional decline (3/3 studies), and overall survival (2/11 studies). A meta‐analysis of four studies indicated an association between PP (≥5 medications) and postoperative complications (overall odds ratio, 1.3; 95% confidence interval [1.3–2.8]). PIM was associated with adverse outcomes in 3 of 11 studies. Conclusion PP is associated with postoperative complications, chemotherapy toxicities, and physical and functional decline. Only three studies showed an association between PIM and outcomes. However, because of inconsistent definitions, heterogeneous populations, and variable study designs, these associations should be further investigated in prospective studies. Implications for Practice Polypharmacy and potentially inappropriate medications (PIM) are prevalent in older adults with cancer. This systematic review summarizes the associations of polypharmacy and PIM with health outcomes in older patients with cancer. Polypharmacy and PIM have been associated with postoperative complications, frailty, falls, medication nonadherence, chemotherapy toxicity, and mortality. These findings emphasize the prognostic importance of careful medication review and identification of PIM by oncology teams. They also underscore the need to develop and test interventions to address polypharmacy and PIM in older patients with cancer, with the goal of improving outcomes in these patients.

Evidence for the Contribution of Gut Microbiota to Age-Related Anabolic Resistance

“…More than 90% of older adults (≥65 years) regularly take at least one medication, and 57% of older women and 44% of older men report using 5 or more medications weekly (i.e., polypharmacy) [ 194 ]. Polypharmacy and the use of inappropriate medications in older individuals is independently associated with functional impairment [ 195 ] and a decline in activities of daily living [ 196 ] that may me mediated, at least in part, through drug-microbiome relationships. Medications and the microbiome have bidirectional interactions; medications may elicit inhibitory or beneficial effects on gut microbes, meanwhile, gut microbes play an active role in drug metabolism [ 197 ].…”

Association of Polypharmacy and Potentially Inappropriate Medications With Physical Functional Impairments in Older Adults With Cancer

“…Although $5 medications is the most commonly used definition in the literature, 3,16 other cutoff values have been used, including 3, 6, 9, or 10 medications. 17 A better understanding of the relationships between polypharmacy/PIMs and physical function in this population could inform the development of interventions to optimize medication use in this population. For example, previous research has demonstrated that pharmacists play a significant role in assessing medication appropriateness, with respect to quality and safety of prescribing.…”

Polypharmacy among Older Advanced Lung Cancer Patients taking EGFR Tyrosine Kinase Inhibitors

“…With regard to survival, there was a significant correlation between the OS and PP in older advanced NSCLC patients. A recent metanalysis of the correlation between PP and survival outcomes for patients on chemotherapy across 11 prospective and retrospective studies [11] showed significant correlations only in 2 studies (1 on ovarian cancer [45] and the other on acute myeloid leukemia), [46] while the remaining 9 studies, including a study on patients taking oral imatinib for chronic myeloid leukemia [38], did not show any correlation between PP and mortality. Our data might suggest that prognostic significance differs according to cancer type and treatment.…”

“…Studies have included only a small numbers of advanced lung cancer patients and have shown relatively high prevalence (7%-80%) of PP among the patients and its negative impact on clinical outcomes [11,16,[34][35][36][37]. However, the heterogeneity of patients' disease states, baseline characteristics, or treatment modalities across target populations or cancer types might impair the applicability of these results to different clinical situations.…”

“…Older cancer patients can suffer from a higher rate of comorbidity, frailty, and geriatric syndrome, putting them at high risk of PP [10] . Both PP and PIM use are attracting attention in the field of oncology with regard to the general geriatric population [11][12][13][14][15]. Studies have shown the prevalence and effect of PP on chemotherapy outcomes, such as survival and adverse events (AEs), in advanced cancer patients [14,[16][17][18].…”