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.