The search identified 137 studies of which 17 studies were eligible for inclusion (Fig. 1). There were no discrepancies between the individual scores of the two screening pharmacists. Eight studies applied a tool not developed for the oncology population or a palliative cancer care population. In two articles, the authors recommended a methodology specific for oncology patients without applying or validating the tool. Since a few studies applied the same tool, in total, nine different tools or guidelines were identified. Table 1 summarizes these tools and guidelines and Table 2 shows the outcomes of the studies applying these tools. All identified tools and guidelines are further described below.
Table 1 Summary of tools and guidelines identified Table 2 Outcomes of PIMs in studies applying tools or guidelines Tools specifically for cancer patients
OncPal
Three of the included studies evaluated the use of the OncPal guideline specifically developed for deprescribing in palliative cancer patients. Lindsay et al. [10] describes the development and validation of this guideline against an expert opinion panel in a single-center study. The OncPal guideline was shown to match the deprescription of 617 medicines in 61 patients with an accuracy of 94% when compared to the expert panel. In the 61 patients, 70% were taking at least one PIM, and of the total medicines that were used in the patient group, 21.4% were assessed as PIMs. The OncPal guideline gives deprescribing advice on 8 classes of drugs. Two other studies also assessed PIMs using the OncPal method (Table 2). Marin et al. [20] compared PIMs prior to and after a palliative care consult in non-curative in patients with cancer. They expanded the medication categories in the OncPal with anticoagulants and benzodiazepine receptor agonists and showed that a palliative care consult could reduce the percentage of PIMs from 21 to 14% in palliative cancer patients. Wenedy et al. [21] assessed the appropriateness of discontinuation of medications in cancer and non-cancer home hospice care patients using OncPal. No absolute amounts of PIMs were measured. However, the use of most of the preventive medications was discontinued in 60 to 70% of the included patients, with proton pump inhibitors being the drug class most often de-escalated or halted.
6-Step method
The 6-step method as proposed by Gonçalves [11] is described in Table 1. This is a systematic method to make deprescribing more efficient and safer. This method was suggested and described in a review. However, it gives no detailed guidance on which drugs for which indications can be safely deprescribed, nor has it been assessed in actual patients.
Steps to deprescribe
Also Sharma et al. [12] propose a stepwise method to deprescribe in older patients with cancer to increase appropriateness and safety during deprescribing (Table 1). These steps should be carried out periodically. This method was recommended for older patients with cancer and did not focus specifically on palliative cancer patients. Furthermore, like the 6-step method described above, this method has not been applied on a patient population.
Futility criteria
Oliveira et al. [13] modified criteria for futility from Fede et al. [14] into a guideline to assess futility with 7 medication categories (Table 1). These criteria were retrospectively applied on data of 448 advanced cancer patients referred to the palliative care service. These patients had a median survival of only 15 days. The authors noted very high numbers of patients that were still on gastric protectants (50%) and statins (97%). It was noted that antihypertensive agents and antidiabetics should be interpreted differently in advanced cancer patients than in other patients, since higher values of blood pressure or blood glucose can be acceptable in this population, if asymptomatic.
Preventative medications
Todd et al. [15] carried out a systematic review into studies determining inappropriate use of preventive medication of 5 drug classes in patients with a life-limiting illness. In this review, they established a list with the most common inappropriate preventive medications used in this population (Table 1). Afterwards, they assessed the frequency of use of these medications in patients with advanced lung cancer in two hospitals (Table 2) [22]. No interventional study with the list of preventative medications has been published to date.
Medications for chronic diseases
Garfinkel et al. [16] described the medication use among end-stage cancer patients at the time of admission to home care hospice (Table 2). Medications that were included were used for chronic diseases. Drugs used for the oncological treatment were excluded. Appropriateness of medication was not assessed, but a stepwise recommendation for deprescribing was formulated based on the observation that at just 2 months before death, 23% of patients were still being treated with 12 or more drugs and 90% were still treated with 6 to 12 drugs.
Tools non-specifically for cancer patients
Beers criteria
The Beers criteria is a frequently used method to deprescribe in the overall geriatric population. Since the first edition, it has been updated many times based on new insights and evidence [17]. The Beers criteria are commonly applied on the palliative cancer population although it has been developed for the geriatric population. Zhou et al. [29] used the Beers criteria to estimate the frequency of six specific classes of PIMs in chemotherapy order templates for hematologic malignancies (Table 2). In 45% of these order templates, medications considered as PIMs by the Beers criteria were found. The authors wanted to draw attention to these potential risks. However, it could also be considered that the Beers criteria are not a perfect match to deprescribe in the cancer population. Karuturi et al. [23] applied the Beers criteria combined with drugs to avoid in the elderly (DAE) to identify PIM use in a cohort of older patients with stage II/III breast and colorectal cancer (Table 2). Also the frequency of these PIMs was evaluated at different time points. The use of PIM was lower at 3–6 months following initiation of chemotherapy when compared to baseline. Hong et al. [25] used the Beers criteria of 2015 to assess the frequency of PIMs in a population of geriatric patients with cancer undergoing first-line palliative chemotherapy (Table 2). However, medications typically used during chemotherapy (e.g., medications for nausea) were excluded. The authors state that modifying of the Beers criteria can be needed for the cancer population since several supportive drugs used during chemotherapy are considered PIMs by the Beers criteria. Nightingale et al. [26] combined 3 deprescribing guidelines: STOPP criteria, DAE, and the Beers criteria. The authors evaluated the frequency of PIMs in a population of ambulatory older adults with cancer. They divided the population based on the use of complementary and alternative medication (CAM). Herbal medications, minerals, or other dietary supplements, excluding vitamins, were considered as CAMs. The prevalence of the use of CAMs was 26.5%. In 2017, the same research group assessed appropriateness of medication use by the Beers criteria in patients who received a comprehensive geriatric oncology assessment and received a pharmacist-led individualized medication assessment and planning (iMAP) intervention [28]. They enrolled 41 patients in their study and identified medication-related problems in 95%. The pharmacists’ interventions reduced the number of medication-related problems by 45.5%. Flood et al. [27] finally applied the Beers criteria to 47 hospitalized older adult cancer patients referred to the acute care for elders unit (Table 1). The frequency of PIMs was determined on admission, and recommendations for deprescribing were made in 28% of patients. Again, the most frequent PIMs identified according to the Beers criteria were in fact drugs used as supportive care during cancer treatment.
STOPP criteria
STOPP criteria have been shown to improve inappropriate medication use in the elderly when applied during hospitalization [18]. Inappropriate medication use is associated with the occurrence of adverse drug events (ADEs) and an intervention using the STOPP criteria can reduce ADEs in older hospitalized patients. Karuturi et al. [24] used these criteria for estimating the use of PIMs in patients with stage II/III breast and colorectal cancer receiving chemotherapy, but found no statistically significant associations by the number of PIMs and clinical outcomes. As described above, Nightingale et al. [26] also used the STOPP criteria combined with 2 other guidelines.
Medication appropriateness index
The medication appropriateness index (MAI) is a questionnaire to assess futility of the drugs used (Table 1). It can be used to determine why the discontinued drug was inappropriate. Domingues et al. [19] applied a modified version of MAI for cancer patients at the time of palliative care transition in a prospective study (Table 2). They included 71 patients and found polypharmacy in 85% of cases. Using the MAI, 28% of drugs used could be suspended.