It’s time for comprehensive polypharmacy reviews for older people with cancer

More often than not, a cancer survivor is an older person; in 2010, 63% of cancer survivors in the UK were aged 65 years or older, and this proportion is expected to increase to 77% by 2040^[1]
. The health of this group is likely to be compounded by a long-term condition considering that, of the 2.5 million people living with cancer in the UK, 70% have at least one long-term condition, with 29% reporting more than three long-term conditions^[2],[3]
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Older people with cancer may take medicines to manage these long-term conditions; their cancer treatments often require supportive care medicines and, as they age, they become more likely to be prescribed several medicines for multimorbidities. This puts them at risk of polypharmacy, where “multiple medications” are prescribed “inappropriately, or where the intended benefit of the medication is not realised”, which could put them at risk of adverse drug reactions and poorer health outcomes^[4]
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Older people presenting to cancer services can expect an oncologist to make decisions about their cancer treatment and secondary care may defer decisions about medication for managing long-term conditions to primary care. However, poor communication about medicines between the sectors can compromise patient safety and effective medicines management^[5]
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Here, we investigate polypharmacy in older people with cancer, and recommend comprehensive medication reviews in this population to address the issue.

Identifying the polypharmacy problem

Many explicit and implicit screening tools to identify polypharmacy have been described in the literature. Explicit tools, such as the Beers criteria and both the ‘screening tool of older people’s prescriptions’ and ‘screening tool to alert to right treatment’ criteria, known as STOPP/START, typically include medicines and/or drug classes, based on expert opinion, consensus and literature review^[6],[7]
. These tools are easy to use and do not usually require clinical expertise; however, medicines related to cancer treatment are generally not included in these reviews. Conversely, implicit tools, such as the medication appropriateness index (MAI) and the ‘NO TEARS’ tool are based on principles for medication review and do not contain drug- or disease-specific lists^[8],[9]
. They rely on expertise and knowledge, and while time-consuming, they encourage a person-centred approach^[10]
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Non-cancer medicines can be disruptive

Through use of these tools, polypharmacy appears to be higher in the cancer population than in the general population, and many studies suggest that most of the problems in these patients could be owing to medication prescribed for long-term conditions.

In 2018, Murphy et al. published their large population-based study that compared the prevalence of polypharmacy (≥5 unique medications) in cancer survivors versus non-cancer controls^[11]
. The results showed that 64% of people in the cancer group had polypharmacy, compared with 52% of people in the non-cancer group.

Meanwhile, Cashman et al. reported that older people with metastatic disease attending outpatient clinics were prescribed a median of 7 (range 1–17) medicines^[12]
. Up to 80% were taking chemotherapy, including cytotoxic therapy, targeted therapy, hormonal therapy and immunotherapy, and 81% were taking one or more preventative medicines, such as anti-hypertensives, lipid lowering agents and antiplatelets. Around 51% of this group experienced side effects caused by long-term condition medicines, which led the authors to question the appropriateness of continuing these medicines in patients with limited life expectancy.

Similarly, Lavan et al. looked at oncology inpatients, 97% of whom had ≥2 chronic conditions; 47% were prescribed ≥6 medications (polypharmacy), and 11% were prescribed ≥11 medications (major polypharmacy)^[13]
. Older patients (≥70 years), when compared with younger patients (<70 years), had higher rates of polypharmacy (63% vs. 38%) and major polypharmacy (19% vs. 7%). More than 21% of admissions were resulting from adverse drug reactions, but these were owing to medications commonly used for long-term conditions, rather than chemotherapy.

Potentially inappropriate medication criteria should be modified for the older cancer population

While the prevalence of polypharmacy appears to be higher in the cancer population, evidence suggests that most of the problems in these patients could be owing to medication prescribed for long-term conditions^[14]
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Supportive care medicines

Chemotherapy usually includes combinations of multiple-drug regimens, which often necessitate supportive care medications such as anti-emetics, corticosteroids, antibacterials, antifungals and antivirals. Benzodiazepines and anticholinergic agents are identified as inappropriate medication in multiple medication screening tools. However, these medication classes are commonly prescribed and essential for managing chemotherapy-induced nausea and vomiting in people receiving chemotherapy^[15]
. Several medications that are considered potentially inappropriate are frequently used as supportive care in chemotherapy services and should not be deemed inappropriate^[16]
. Perhaps potentially inappropriate medication criteria should be modified for the older cancer population.

In a study of 500 participants, Maggiore et al. evaluated the prevalence of polypharmacy and potentially inappropriate medication, and investigated associations between these factors and chemotherapy-related adverse events in older people undergoing treatment^[16]
. While polypharmacy and potentially inappropriate medication use were common, reassuringly, there were no associations with chemotherapy-related adverse events or hospitalisation during chemotherapy. Polypharmacy and potentially inappropriate medication use was acknowledged to significantly increase non-chemotherapy adverse drug reactions and falls, which could negatively affect a patient’s quality of life.

Challenges to reducing inappropriate polypharmacy

Polypharmacy can be harmful to older people with cancer, but there is limited information to support prescribers to make evidence-based decisions in this group because it is underrepresented in clinical trials^[17]
. The UK National Cancer Research Institute made recommendations to improve outcomes for older people with cancer, including comprehensive geriatric assessment, integrating geriatric teams in oncology, involving patients in their care, and putting a geriatric focus on industry trials^[18]
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Established medication screening tools, such as Beers criteria, STOPP/START and MAI, have been extensively used to identify potentially inappropriate medication in older people, but their utility in cancer patients is limited^[6],[7],[8]
. When considering the appropriateness of medication in cancer patients, prescribers must take into account not only the number of medications, but also consider life expectancy, goals of cancer treatment, intent of treatment (curative or palliative) and quality of life^[19]
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After a comprehensive review evaluating several medication screening tools in older people with cancer, Whitman et al. could not endorse the use of a single tool, but instead supported the concurrent use of Beers criteria, STOPP/START and MAI in this population^[15]
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While specialist oncology pharmacists undergo specific training, there remains a gap in the knowledge and skills required to manage complex older people

Similarly, the National Comprehensive Cancer Network (NCCN) clinical practice guideline on older adult oncology advises conducting a medication review as part of a comprehensive geriatric assessment, and recommends the use of all three tools to identify medications that pose high threat/low benefit. The NCCN guidelines also include a comprehensive list of medications commonly used for supportive care that are of concern in older patients^[20]
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Polypharmacy and the cancer workforce

A 2016 review suggests that the current UK healthcare workforce is not well prepared to meet the challenges of an ageing population with cancer^[21]
. While specialist oncology pharmacists undergo specific local training to demonstrate competency, there remains a gap in the knowledge and skills required to manage complex older people^[22]
. Educational needs should be reviewed to meet the complex needs of older people, which may extend beyond cancer care, and cancer care pharmacists should work closely with pharmacists who specialise in the care of older people. We should integrate these specialities to improve medicines optimisation for these patients; and pharmacy professionals should cultivate leadership in geriatric oncology, through programmes like the King’s College London’s Older Person’s Fellowship^[23]
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Improving the care of older people with cancer

Our recommendations — for policymakers and healthcare professionals working in the care of older people, and the care of cancer — include:

1. Recognise polypharmacy in people with cancer as an emerging issue;
2. Identify high-risk patients (for example, patients with frailty and existing polypharmacy) whose concurrent medicines for cancer and long-term conditions may negatively affect their health;
3. Realign education, training and practice of specialist oncology pharmacists to match the population’s demographic shift;
4. Explore integration of geriatric and oncology skills;
5. Provide recommendations for doctors and pharmacists working in general practice about how to optimise medicines for older people living with cancer, during and after cancer treatment;
6. Develop methods of referral for patients who cannot be managed in primary care;
7. Develop and evaluate a medication screening tool specifically for older people with cancer.

Know the current tools

There is no single explicit medication review tool that contains a comprehensive list of medicines for people undergoing cancer treatment with other long-term conditions. Until our recommendations can be implemented, healthcare professionals should familiarise themselves with the tools and use them to improve the lives of older people with cancer.