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Analysis Underscores Risks of Polypharmacy in Elderly Patients With Cancer


Results of a secondary analysis of a randomized controlled trial emphasize the risks of polypharmacy with regard to prescription and nonprescription medications.

Research published in The Oncologist highlights the burden of polypharmacy, potentially inappropriate medications (PIMs), and potential drug-interactions (DDIs) and drug–cancer treatment interactions (DCIs) among vulnerable older patients with cancer.

Of note, the study included nonprescription medications (which are often not accounted for in most polypharmacy studies) and found these OTC drugs are frequently PIMs and/or involved in potential DDIs/DCIs, authors wrote.

Polypharmacy is defined as the concurrent use of multiple medications and is common among older adults with cancer, researchers explained, as older individuals are more likely to be prescribed “multiple medications due to age-related multimorbidity, frailty, and other geriatric syndromes” than their younger counterparts.

Care fragmentation across multiple specialties, in addition to prescribing cascades aimed at mitigating adverse effects of other medications, also contribute to high rates of polypharmacy in this population.

Both polypharmacy and PIMs are associated with mortality, falls, and hospitalizations in older adults, and PIMs can even decrease tolerance of cancer treatments and worsen patient outcomes.

To better understand polypharmacy, PIMs, DDIs, and DCIs in an older population with cancer, researchers assessed data from 718 individuals recruited to a national prospective cluster-randomized trial of geriatric assessment (GA), conducted in community oncology practices.

Patients were enrolled between July 2014 and March 2019 and completed a polypharmacy log. All participants were 70 years or older, had a diagnosis of with incurable stage III or IV solid tumor cancer or lymphoma, and were planning to start a new cancer regimen with a high risk of grade 3 to 5 toxicity. Participants also had to be impaired in at least 1 GA domain apart from polypharmacy.

“Polypharmacy was defined as using ≥5 regular medications while excessive polypharmacy was defined using ≥10 regular medications,” authors wrote.

Mean patient age was 77.2 years and 43.3% were female; the majority (n = 628) were non-Hispanic White and had stage IV cancer (n = 628).

Analyses revealed:

  • Polypharmacy, excessive polypharmacy, and at least 1 PIM were identified in 61.3%, 14.5%, and 67.1% of patients, respectively.
  • Cardiovascular medications were the most prevalent (47%), and nonprescription medications accounted for 26% of total medications and 40% of PIMs.
  • One-quarter of patients had at least 1 potential major DDI not involving cancer treatment, and 5.4% had at least 1 potential major DCI.
  • Each additional medication increased the odds of a potential major DDI and DCI by 39% and 12%, respectively; each additional prescription medication increased these odds by 40% (P < .01) and 19% (P < .01), respectively.
  • Patients with polypharmacy were more likely to be older (mean age, 77.5 vs 76.7 years), have a functional impairment (62.1% vs 50.0%), be physically impaired (94.8% vs 90.1%), have significant comorbidity (78.0% vs 50.7%), and have impaired psychological status (32.7% vs 21.9%).

Hypertension, arthritis, heart diseases, and diabetes were the most common noncancer comorbidities in the cohort, and each patient took a median of 5 medications. Common nonprescription medications included proton pump inhibitors, nonsteroidal anti-inflammatory drugs, and antihistamines.

“Older adults may incorrectly assume that OTC medications are safe for them, and providers may be unaware of the full complement of medications their older patients are taking if a prescription was not generated,” authors wrote.

“This study, therefore, helps delineate the size and shape of a problem underrecognized by both providers and patients, and highlights an opportunity for improved medication reconciliation, patient and caregiver education, deprescribing, and other interventions,” they added.

Around 10% of hospitalizations among older individuals are associated with adverse drug events with most considered preventable, while in those undergoing chemotherapy, polypharmacy has been linked with an up to 114% increased risk of unplanned hospitalization.

The nature of the study, in that it is a secondary analysis of a randomized clinical trial, marks a significant limitation.

“More work is urgently needed to implement and evaluate interventions addressing polypharmacy and PIMs in older adults with cancer, particularly those initiating cancer treatment,” researchers concluded.


Ramsdale E, Mohamed M, Yu V, et al. Polypharmacy, potentially inappropriate medications, and drug-drug interactions in vulnerable older adults with advanced cancer initiating cancer treatment. Oncologist. Published online March 28, 2022. doi:10.1093/oncolo/oyac053

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