Abstract
Aim: Polypharmacy (PP) is a common problem among the older adults and has a potential effect on health-related problems. However, the significance of PP in older advanced non–small cell lung cancer (NSCLC) patients and those on oral molecular-targeted anticancer agents is unclear.
Methods: This retrospective study reviewed the records of 334 advanced NSCLC patients who underwent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. PP was defined as >=5 concomitant medications. Potentially inappropriate medication (PIM) use was measured using the updated screening tool of older people’s prescriptions (STOPP) ver. 2 criteria. We also estimated survival distributions using the Kaplan–Meier method, compared between–group differences using the log-rank test, explored potential predictors of survival using Cox regression, and performed cluster analysis to identify factors affecting multiple-medication use.
Results: The PP and PIM use prevalence was 38.4% and 31.9%, respectively. The median overall survival (OS) for PP(+) and PP(–) patients was 19.4 months (95% CI = 14.1–24.8) and 27.3 months (95% CI = 22.6–36.4), respectively (P < 0.001). Multivariate analysis revealed a significant correlation between PP and OS. The frequency of unexpected hospitalization during EGFR-TKI treatment was higher in PP(+) compared to PP(–) patients (49.4% vs. 29.4%; P= 0.0032; OR = 2.34; 95% CI = 1.31–4.23).
Conclusion: PP is an independent prognostic factor in older NSCLC patients taking EGFR-TKIs. PP can be used as a simple indicator of such patients’ comorbidities and symptoms or as a predictive marker of unexpected hospitalization during treatment.
Introduction
Polypharmacy (PP) is a simple summary of a patient’s prescription status in terms of the number of drugs concurrently prescribed to him or her. PP is a common problem among older patients, with a potential effect on health-related problems.[1-3] PP can lead to undesirable clinical outcomes, such as adverse drug reactions, drug–drug interactions, reduced adherence to drugs, and excessive health resource use[4]. Potentially inappropriate medication (PIM) use reflects the prescription appropriateness and not just in terms of the numbers of drugs prescribed[5, 6]. PIM use is evaluated on the basis of several criteria, such as the screening tool of older people’s prescriptions (STOPP), the screening tool to alert to right treatment (START),[7] Beers Criteria,[8] and the medication appropriateness index (MAI)[9].
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[11-15]. Studies have shown the prevalence and effect of PP on chemotherapy outcomes, such as survival and adverse events (AEs), in advanced cancer patients[14, 16-18]. The mortality in lung cancer, which accounts for ~20% of all cancer deaths, is high compared to other cancers. The reason is that few lung cancer cases are diagnosed at the early stage[19, 20], and ~60% of lung cancer patients present with metastasis at diagnosis, which is much higher compared to other common cancers (e.g., 22% for colorectal and 6% for breast cancer)[21]. The most common metastatic site is bone, followed by the lungs, brain, adrenal glands, and liver [22]. Distant metastasis along with a primary lesion and its invasion to adjacent structures cause pain and dyspnea. Therefore, multiple medications are often required control symptoms in advanced cancer patients. Studies have shown a higher rate of opioid use among lung cancer patients compared to other cancers[23-25]. In addition, older cancer patients are naturally prone to PP because of the relatively high prevalence of noncancer multimorbidity with aging. Lung cancer has a median onset age of ~70 years and is therefore commonly observed in the elderly[26].
However, studies have not clearly described the clinical significance of PP in advanced lung cancer patients and have included only a small number of patients. In addition, data on patients undergoing novel therapy, such as oral molecular-targeted anticancer agents (e.g., epidermal growth factor receptor tyrosine kinase inhibitors [EGFR-TKIs]), are scarce[27]. Also, the applicability of updated STOPP ver. 2 criteria[7] as an assessment tool of PIM use in oncology practice has never been investigated. Therefore, this study investigated the prevalence and effect of PP and PIM use according to STOPP ver. 2 (PIM-STOPP v2) on outcomes for older advanced non–small cell lung cancer (NSCLC) patients treated with EGFR-TKIs.