Polypharmacy Associated With Functional Decline in Older Patients With Advanced Cancer

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Polypharmacy (ie, the concurrent use of eight or more medications) and potentially inappropriate medications may be associated with functional impairment in older adults with advanced cancer, according to research presented by ­Mostafa Mohamed, MBBCh, at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) 2019 Annual Meeting in San Francisco.1

Mostafa Mohamed, MBBCh

Mostafa Mohamed, MBBCh

Polypharmacy is a significant health problem in the geriatric population. Older adults with cancer are at an even higher risk of polypharmacy, due to multiple comorbidities and the complexity of their treatment regimens. Previous data have shown the prevalence of polypharmacy to be as high as 92% in this population.2 Related to polypharmacy is the issue of potentially inappropriate medications, defined as drugs with a high risk-to-benefit ratio.

Functional and physical impairments are predictive of chemotherapy toxicities and lower survival,3,4 so maintenance of good physical and functional status is important in older adults with cancer. However, the relationship of polypharmacy and potentially inappropriate medications with physical functioning has thus far been understudied in this population.

Study Details

According to Dr. Mohamed, a geriatric oncology postdoctoral fellow at the University of Rochester in Rochester, New York, the definition of polypharmacy varies in the literature. Although the most commonly used definition refers to five or more concurrent medications, there is no consensus on the optimal cutoff number of medications to define polypharmacy in older adults.

“We found that receiving eight or more medications was the optimal cutpoint to define polypharmacy.”
— Mostafa Mohamed, MBBCh

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In this analysis, he and his colleagues aimed to determine the optimal cutoff value of polypharmacy in relation to validated measures of physical functioning. They also examined the association of polypharmacy and potentially inappropriate medications with impairments in physical functioning among older adults with advanced cancer.

The investigators conducted a cross-sectional analysis of baseline data from a national geriatric assessment randomized study ( identifier NCT02054741, Primary Investigator: Supriya G. Mohile, MD). Enrolled patients were aged 70 years or older, with a diagnosis of an incurable stage III or IV solid tumor or lymphoma and one or more impaired domains on geriatric assessment. Patients were scheduled to start a new cancer treatment regimen within 4 weeks from the time of enrollment.

Prior to chemotherapy, all prescription and over-the-counter medications received within 2 weeks of study enrollment were captured in a polypharmacy log. Antineoplastic and supportive care medications were excluded from the medication count. Potentially inappropriate medications were categorized using the 2015 American Geriatrics Society Beers Criteria, a tool used to assess inappropriate prescribing in older adults by outlining potentially problematic medications, potential drug-disease interactions, and combinations of medicines known to cause harmful drug-drug interactions.

Three patient-reported validated functional measures were assessed. The Older Americans Resources and Services Physical Health (OARS PH) survey measured patient difficulty with 10 items related to physical activity; the Activities of Daily Living (ADL) six-item scale assessed difficulty with basic activities like bathing and eating; and the Instrumental Activities of Daily Living (IADL) seven-item scale assessed instrumental activities, such as using the telephone and shopping. On each scale, impairment was defined as the inability to perform one or more activities.

A total of 439 patients with a mean age of 77 were evaluated. Approximately 71% of patients were receiving 5 or more concurrent medications, 43% were receiving 8 or more, and 24% of patients were taking 10 or more (commonly considered “extreme polypharmacy”). More than 70% of patients were impaired according to the OARS PH scale, and 55% were impaired on the IADL scale.

The researchers also observed a high prevalence of potentially inappropriate medications: 62% of the study population received at least one medication considered inappropriate by the Beers Criteria. The most commonly used were proton-pump inhibitors (36%), benzodiazepines (24%), nonsteroidal anti-inflammatory drugs (18%), and first-generation antihistamines (15%).

Eight or More Medications Associated With Impairment

Polypharmacy and potentially inappropriate medications were independently associated with functional impairment in the study population. “We found that receiving eight or more medications was the optimal cutpoint to define polypharmacy,” Dr. Mohamed reported.


  • Polypharmacy and the use of potentially inappropriate medications are prevalent in older adults with cancer, but associated outcomes are understudied.
  • In a cohort of patients aged ≥ 70 years with advanced cancer, defining polypharmacy as ≥ 8 medications identified patients with functional impairments. Potentially inappropriate medications were also associated with impairments in these patients.
  • Optimizing medication use may reduce functional decline and improve quality of life in this patient population.

On multivariate analysis, being on eight or more medications was associated with OARS PH and ADL impairments (P < .05), and potentially inappropriate medication was associated with OARS PH and IADL impairments (P < .05). Polypharmacy defined as five medications was not associated with physical outcome measures.

“To our knowledge, this is the first study demonstrating that potentially inappropriate medications are associated with physical functional impairment in older adults with cancer,” he reported.

According to the researchers, optimizing medication use may reduce the risk of functional decline and improve quality of life and survival in this population. They maintain that future studies should evaluate the effects of decreasing polypharmacy and potentially inappropriate medications on improving physical function in older adults with cancer.

This study was conducted by researchers in the Geriatric Oncology Program at the Wilmot Cancer Institute at the University of Rochester and includes Drs. Mostafa Mohamed, Erika Ramsdale, Huiwen Xu, Melissa Loh, and Supriya Mohile.

DISCLOSURE: Dr. Mohamed reported no conflicts of interest.


1. Mohamed M, Patil A, Xu H, et al: Association of polypharmacy and potentially inappropriate medications with physical function in older patients with cancer receiving chemotherapy. 2019 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. Abstract JS15. Presented June 23, 2019.

2. Maggiore RJ, Gross CP, Hurria A: Polypharmacy in older adults with cancer. Oncologist 15:507-522, 2010.

3. Extermann M, Boler I, Reich RR, et al: Predicting the risk of chemotherapy toxicity in older patients. Cancer 118:3377-3386, 2012.

4. Maione P, Perrone F, Gallo C, et al: Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy. J Clin Oncol 23:6865-6872, 2005.