Clinicians need to stay current with polypharmacy concerns

Anew study raises an alarm over polypharmacy, an issue that is not new but may become more worrisome because of an aging population and a myriad of new drugs coming to market, including cancer drugs. The study appears in Cancer (doi:10.1002/cncr.34642).

Corresponding author Erika Ramsdale, MD, MS, geriatric oncologist and associate professor of hematology/oncology in the Department of Medicine at the University of Rochester in Rochester, New York, warns that although there is some evidence that cancer treatment outcomes may be affected by taking multiple medications and/or potentially inappropriate medications (PIMs), “the research is still very sparse.”

Dr Ramsdale says that the main goal of this new study was to examine the associations between polypharmacy, PIMs, and potential drug–drug interactions (PDIs) and adverse cancer treatment outcomes in a large national cohort of older adults with advanced cancer. The authors note that polypharmacy and PIMs have suspected roles in many adverse events in older patients with cancer, including toxicities, but cause and effect links have been unclear.

This secondary analysis uses data from an earlier nationwide, multicenter, cluster-randomized study by the same team that appeared in The Lancet (doi:10.1016/S01406736(21)01789-X). Known as the Geriatric Assessment for Patients 70 Years and Older (GAP70+) study, it assessed clinician-rated grade 3–5 chemotherapy toxicity in older adults with advanced cancer who were undergoing a new cancer treatment regimen.

In the Cancer study, the authors note that a host of variables exist beyond the age and possible disabilities of the patients. Other factors that can contribute to difficulties include health care system–level issues, such as poor transitions of care, interdepartmental communication, multiple pharmacies, and “prescribing cascades.”

There were 718 patients enrolled in the study between July 2014 and March 2019 who had provided written consent. The subjects ranged in age from 70 to 94 years, were predominantly male (56.4%) and non-Hispanic White (87.5%), and had a stage III/IV solid tumor or lymphoma (87.5%). Gastrointestinal cancer was the most common type (246 patients; 34.3%), and it was followed by lung cancer (180 patients; 25.1%).

Four hundred forty of the 718 patients (61.3%) were taking five or more medications, 198 (27.6%) were taking eight or more, and 104 (14.5%) were taking more than 10. The researchers found that 447 patients (62.3%) received one or more PIMs according to the 2019 American Geriatrics Society Beers Criteria (range, 0–8 PIMs), and 206 (28.7%) received at least one PIM according to the Screening Tool of Older Persons’ Prescriptions (STOPP) criteria. All told, there were 482 patients (67.1%) with one or more PIMs.

There were 177 patients who had at least one potentially major PDI (category D or X).

The researchers found that the mean number of grade 2 or higher toxicities was 8.0. They also found that 178 of the study participants were hospitalized within 3 months of their treatments. For those patients prescribed fewer than eight medications, the mean number of grade 2 or higher toxicities was 7.7, which escalated to 9.8 for patients taking eight or more medications.

Dr Ramsdale says that a key finding of the study is that it suggests a link between medications taken for noncancer diagnoses and how well older patients tolerate cancer treatment. “You might initially think that people taking more medications have more health problems, and therefore might do worse with cancer treatment [because of those problems], but we adjusted for … other health conditions in our mathematical models.” Specifically, she points out that taking eight or more medications was associated with a higher median number of chemotherapy toxicities. In addition, the use of PIMs was associated with increased hospitalization, and drug–drug interactions were associated with early discontinuation of cancer treatment.

“This study adds new information in the realm of cancer,” says William Dale, MD, PhD, the George Tsai Family Chair in Geriatric Oncology, director of the Center for Cancer and Aging, and professor and vice-chair for academic affairs in the Department of Supportive Care Medicine at City of Hope in Los Angeles, California. “While the issue of polypharmacy in geriatrics is fairly well-known, in the cancer world there is very little data to guide us on … the use of medications that aren’t cancer-directed. So, in that way, this is new and important, with a much more granular insight about how we need to think about polypharmacy in older adults with advanced cancer.” (Although Dr Dale did not participate in the Cancer study, he is a coauthor of the study in The Lancet.)

Dr Ramsdale says that this study is unique because it looked specifically at older, more vulnerable, or frail adults receiving treatment in their communities rather than at academic centers. “We often don’t have data about these patients even though they represent what is more typical for older adults receiving cancer treatment,” she says.

Dr Ramsdale adds that the detailed information they were able to gather about exactly what medications the patients were taking, how they were doing during cancer treatment, and how much cancer treatment they received was valuable: “This information is often unavailable to researchers.” For example, she notes, they have information not only about patients’ prescription medications but also about which over-thecounter medications they were taking. “The data collected allowed us to develop a very detailed picture of the total medication burden as well as the full scope of potential interactions between the various therapies the patients were taking,” she says.

Dr Dale says that many older adult patients begin cancer therapy already on multiple medicines for a variety of issues, and clinicians might “defer and continue them” without considering possible ramifications. “It might be better to check [with the patient’s primary care physician] and see if the patient can stop taking them during cancer treatment, because the more medicines you take, the more likely it is that that you’ll have unexpected problems.”

He adds that the problem could become even more acute with so many new medicines, including new cancer drugs, being introduced. “In some cases, we don’t have enough data to understand if (potentially) there are any avoidable adverse interactions.”

One place where clinicians can check for guidance on drug interactions is the website deprescribing.org— a site developed by experts in treating older adults. “They provide guidance on general principles for appropriately stopping medications,” says Dr Dale.

There is also the common dilemma of determining which physician is in charge of managing prescriptions and which physician is the correct one to coordinate medications for patients as they enter into oncology care. “It might be that no one wants to touch the medicines from the other clinicians,” says Dr Dale. He recommends that experts in overall care for older adults, such as geriatricians, take the lead. “Our expertise in both polypharmacy and care coordination issues allows us to take responsibility for needed reconciliation across different specialties.”

Dr Ramsdale agrees. “Cancer treatment decisions are complex, particularly in older adults where we don’t have as much data. This research suggests that patients and their care teams should be discussing their other medications in light of a cancer diagnosis and treatment decision-making.”

Dr Ramsdale also believes that there may be opportunities to reconsider some medications or adjust regimens and perhaps reduce some of the risk of cancer treatment toxicity and or increase the cancer treatment’s effectiveness. “To validate the result sof this study, we need to [examine] prospective interventions, suchas ‘de-prescribing’ interventions, to determine if these help patients to better tolerate and benefit from their cancer therapies,” she says.