|ORIGINAL ARTICLE: GERIATRIC ONCOLOGY SECTION
|Year : 2021 | Volume
| Issue : 1 | Page : 67-73
Polypharmacy and potentially inappropriate medication use in older Indian patients with cancer: A prospective observational study
Vanita Noronha1, Anant Ramaswamy1, Shreya Chandrashekhar Gattani1, Renita Castelino2, Manjunath Nookala Krishnamurthy2, Nandini Menon1, Vijay M Patil1, Vikram S Gota2, Shripad Banavali1, Kumar Prabhash1
1 Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra, India
2 Department of Clinical Pharmacology, ACTREC, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra, India
|Date of Submission||24-Feb-2021|
|Date of Decision||02-Mar-2021|
|Date of Acceptance||03-Mar-2021|
|Date of Web Publication||26-Mar-2021|
Professor and Head, Department of Medical Oncology, Tata Memorial Hospital, Parel, Homi Bhabha National Institute, Mumbai - 400 012
Source of Support: None, Conflict of Interest: None
Background: Polypharmacy and the use of potentially inappropriate medications (PIMs) are important issues in older patients with cancer.
Objectives: We aimed to study the prevalence of polypharmacy, and the use of PIMs, including the peri-chemotherapy supportive care regimens in older Indian patients with cancer.
Materials and Methods: This was an analysis of a prospective observational study of patients aged 60 years and over with a diagnosis of malignancy who were assessed in the geriatric oncology clinic at the Tata Memorial Hospital (Mumbai, India). Patients on five or more medications were considered to have polypharmacy; excessive polypharmacy was defined as ten or more medications and PIMs were defined and categorized according to the Beers criteria.
Results: Between June 2018 and October 2020, 285 patients were enrolled in the study. Polypharmacy was noted in 55% of the patients and excessive polypharmacy in 13%. Polypharmacy was noted in 70% of the patients with lung cancer, compared to 45% for other malignancies, P < 0.001. Unindicated medications such as vitamins and calcium were being taken by 20% of the patients and 23% were taking alternative medications (ayurvedic/homeopathic/naturopathic). Eighty percent of the patients were taking PIMs, commonly proton-pump inhibitors (33%) and tramadol (30%). The median number of PIMs was 2 (interquartile range, 1–2). Of the peri-chemotherapy supportive care medications, 53% were potentially inappropriate, commonly intravenous antihistamines in 39%, histamine H2 blockers in 15%, and steroids in 12%.
Conclusions: Polypharmacy and PIM use are common problems in older Indian patients with cancer. Recognizing the problem and taking steps to ensure safe medication prescription practices should be a priority.
Keywords: Geriatric, older, polypharmacy, potentially inappropriate medications PIM, elderly
|How to cite this article:|
Noronha V, Ramaswamy A, Gattani SC, Castelino R, Krishnamurthy MN, Menon N, Patil VM, Gota VS, Banavali S, Prabhash K. Polypharmacy and potentially inappropriate medication use in older Indian patients with cancer: A prospective observational study. Cancer Res Stat Treat 2021;4:67-73
|How to cite this URL:|
Noronha V, Ramaswamy A, Gattani SC, Castelino R, Krishnamurthy MN, Menon N, Patil VM, Gota VS, Banavali S, Prabhash K. Polypharmacy and potentially inappropriate medication use in older Indian patients with cancer: A prospective observational study. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Jun 21];4:67-73. Available from: https://www.crstonline.com/text.asp?2021/4/1/67/312110
| Introduction|| |
The number of older persons is increasing globally. According to a United Nations report, the proportion of persons in the age group of 60 years and older will double between 2007 and 2050 and the actual number will triple, possibly reaching approximately two million by 2050. The total population of India in 2020 was estimated to be 1.38 billion, 8.5% of whom were over 60 years old. By 2050, the proportion of Indians over the age of 60 years is expected to rise to 20%, making this group more populous than persons below the age of 15 years. It has been estimated that the number of cases of cancer in older Indian persons will increase from 0.6 million in 2020 to 1.3 million in 2050. Thus, the older adult population will form a large proportion of our oncology practice, and we need to learn how best to take care of our older patients with cancer.
Older patients with cancer often have several comorbidities requiring multiple medications. In a prospective Swedish study on 1,742,336 persons aged ≥65 years, the average number of medications taken was 4.6 (standard deviation, 4); 44% of the persons were taking five or more drugs (polypharmacy), and the prevalence of excessive polypharmacy (ten or more drugs) was 11.7%. The problems with polypharmacy include drug-drug interactions, increased risk of falls, and often unsuspected adverse effects. Various medications are considered inappropriate or potentially inappropriate in older persons because they are not well tolerated based on altered pharmacodynamics/pharmacokinetics, drug-drug interactions, or drug-disease interactions. According to the Beers criteria that were pioneered by Dr. Mark Beers in 1991, potentially inappropriate medications (PIMs) refer to medicines that are best avoided in older adults, as a general rule or in particular defined situations, for example, in adults with a particular disease or condition and in adults with impaired renal function. The current version of the Beers criteria was updated and published by the American Geriatrics Society in 2019.
At the Tata Memorial Hospital in Mumbai, India, we have established a geriatric oncology clinic in which we evaluate older patients with cancer. As part of the geriatric assessment, we record the medications and the chemotherapy plan of the patients. We aimed to study the prevalence of polypharmacy and PIM use in our patients. We also aimed to determine which the commonly prescribed PIMs were, and whether any of the supportive care medications given before and immediately following chemotherapy (peri-chemotherapy medicines) were PIMs.
| Materials and Methods|| |
General study information
In June 2018, we started the geriatric oncology clinic at the Tata Memorial Hospital (Mumbai, India) in which we evaluated older patients with cancer and performed a geriatric assessment. The data were prospectively entered into an Excel sheet and subsequently transferred to the Statistical Package for the Social Sciences (SPSS). On March 20, 2020, the Institutional Ethics Committee of Tata Memorial Hospital (IEC-III) granted approval for the observational study titled “Retrospective and prospective analysis of the results of a comprehensive geriatric assessment of older patients with cancer who have been evaluated in the geriatric oncology clinic at Tata Memorial Hospital,” project number 900596. The IEC granted a waiver of the requirement to obtain consent from the patients who had already been evaluated (retrospective portion of the study). Following approval of the study, written informed consent was taken from all patients before enrollment in the study. The study was registered with the Clinical Trials Registry-India, CTRI/2020/04/024675. The study was conducted according to the ethical guidelines established by the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice and the Central Drugs Standard Control Organization. There was no funding for the study.
We included patients aged 60 years and older with a diagnosis of malignancy who had been referred to the geriatric oncology clinic for assessment. Patients or caregivers who refused to undergo the geriatric assessment and those with an Eastern Cooperative Oncology Group performance status of 4 were excluded.
The two primary aims of the study were to describe the incidence of non-oncologic vulnerabilities in our older patients with cancer in the domains of function, falls, comorbidities, social, psychological, cognition, and nutrition; and to describe the occurrence of polypharmacy and PIM use. We have earlier reported the incidence of non-oncologic vulnerabilities. In this manuscript, we report the second part of the primary objective of the study, i.e., the occurrence of polypharmacy and PIM use.
Polypharmacy was defined as patients who were taking five or more medications at the time of assessment in the geriatric oncology clinic. Excessive polypharmacy was defined as taking ten or more medications. PIMs were defined as medicines that were preferably avoided in older persons or could be substituted by safer alternatives and were only to be used if the benefits clearly outweighed the risks. We used the Beers criteria to classify PIMs into five major categories, including medications that were considered potentially inappropriate in most older adults; medications considered potentially inappropriate in the presence of some diseases/syndromes, for example, heart failure, syncope, delirium, dementia/cognitive impairment, falls/fractures, and renal dysfunction (glomerular filtration rate <30 cc/min); medications that were to be used with caution; medications that if used together could lead to undesirable drug-drug interactions; and medications that required dose adjustment based on the renal function, for example, pregabalin and gabapentin. In patients who were at the end of life, and had been referred to the palliative care department, none of the medications were considered PIMs, as the benefits of the medicines (analgesics, sedatives, etc.) were assumed to outweigh the potential harms.
We asked the patients and caregivers for the list of medications that had been prescribed. We checked the hospital electronic medical records and the online prescription system for any medications that may have been prescribed in the hospital. We also recorded the over-the-counter allopathic medications, and the use of alternative medications. Combination medications were counted based on the individual constituent medications, for example, narcodol was counted as three medications, i.e., tramadol, paracetamol, and domperidone. Analgesics, other medicines that were taken on a routine basis, and non-prescription over-the-counter medications were included in the count of the patient's medications. We did not include the alternative medications in the total count of medications.
In patients who were planned for chemotherapy, the chemotherapy medications and the supportive care medications were not counted in the total number of patient medications (when evaluating for the presence of polypharmacy), however, we did evaluate the supportive care medications prescribed when assessing for the presence of PIMs. Similarly, antibiotics and other short-term prescriptions were not included in the list of the patient's medications, however, they were evaluated for potential inappropriateness.
As part of the geriatric assessment, we asked and recorded the presence of various symptoms/syndromes that had been included in Beers criteria, for example, insomnia, constipation, symptoms of prostatism, or urinary incontinence. We calculated the creatinine clearance by the Cockcroft–Gault formula, based on the patient's age, sex, weight, and serum creatinine.
As this was an observational study, there was no sample size calculation; we included all patients who fulfilled the study eligibility criteria within the study period.
Statistics were performed in IBM SPSS Statistics for Windows, version 20.0. Armonk, NY, USA: IBM Corp. We used descriptive statistics with absolute numbers and percentages. The association between the presence of comorbidities (as assessed by the Charlson Comorbidity Index or the Cumulative Illness Rating Scale-Geriatrics, the type of cancer and the presence of polypharmacy) and the presence of polypharmacy/PIM use was assessed using the Chi-square test.
| Results|| |
Between June 2018 and October 2020, we enrolled 285 patients in the study. The flow of patient enrollment and evaluation is provided in [Figure 1]. The median age was 70 years (range, 60–100). There were 228 males (80%); 77% of the patients had comorbidities including hypertension in 127 (45%), diabetes in 76 (27%), heart disease in 47 (17%), and chronic obstructive pulmonary disease/asthma in 41 (14%). All patients had solid tumor malignancies, most commonly lung cancer in 112 (39%) and gastrointestinal (GI) in 102 (36%). The intent of therapy was palliative in 163 (57%).
|Figure 1: Flow of patient enrollment and evaluation. (ACRONYMS: ECOG PS-Eastern Cooperative Oncology Group performance status)|
Click here to view
Number of medications
Nineteen patients (7%) were on no medications. One hundred and twenty-eight patients (45%) were taking between 0 and 4 medicines. Polypharmacy was noted in 157 patients (55%); excessive polypharmacy was noted in 37 patients (13%). The median number of medicines taken was 5 (interquartile range [IQR], 2–8). There was a significant association between the presence of polypharmacy and comorbidities, P < 0.001. Based on the type of primary tumor, polypharmacy was noted in 70% of the patients with lung cancer, 45% of the patients with GI cancers, 40% of the patients with head-and-neck cancer, and 52% of the patients with genitourinary primaries. Significantly more patients with lung cancer (70%) were noted to have polypharmacy as compared to patients with other malignancies (45%), P < 0.001.
Potentially inappropriate medications
Two hundred and twenty-eight patients (80%) were on PIMs. The median number of PIMs was 2 (IQR, 1–2). The most commonly prescribed PIMs included proton-pump inhibitors (PPI) in 93 (33%) and tramadol in 84 (30%). The details of the PIMs prescribed are provided in [Table 1] and [Figure 2]. Unindicated medications were being taken by 56 (20%) patients, specifically multivitamins/iron supplements in 49 (17%), calcium in 8 (3%), and statins in 5 (2%).
|Figure 2: The most commonly prescribed potentially inappropriate medications in older Indian patients with cancer|
Click here to view
|Table 1: The potentially inappropriate medications noted in our cohort of older Indian patients with cancer, along with the category of inappropriateness as per Beers criteria and the reasons why the medicines should be avoided|
Click here to view
Of the 186 patients in whom the history of using alternative medicines was documented, 43 patients (23%) reported use: ayurvedic – 28 (15%), homeopathic – 12 (7%), and nutritional supplements – 3 (2%). Based on the type of primary tumor, PIM use was noted in 85% of the patients with lung cancer, 81% of the patients with GI cancers, 79% of the patients with head-and-neck cancer, and 63% of the patients with genitourinary primaries. There was no significant association between the type of primary tumor and the use of PIM, P = 0.06.
Chemotherapy and peri-chemotherapy supportive care medications
Systemic therapy was planned or started in 234 patients, of which 63 patients were on oral medications such as tyrosine kinase inhibitors, capecitabine, or intravenous targeted agents (nimotuzumab) that were administered without premedications. Thus, 171 patients were planned for a variety of systemic therapy regimens that required a gamut of supportive care medications. The most common chemotherapy regimens were paclitaxel with platinum in 61 (36%), and pemetrexed with platinum in 28 (16%). The peri-chemotherapy supportive care medications that were administered as pre-chemotherapy and in the immediate post-chemotherapy period, included intravenous steroids in 150 (88%), oral steroids in 8 (5%), intravenous antihistamines in 66 (39%) including pheniramine in 57 patients (33%) and promethazine in 9 patients (5%), intravenous atropine in 7 (4%), intravenous histamine H2 blockers in 70 (41%), intravenous PPI in 8 (5%), oral PPI in 5 (3%), and oral olanzapine in 15 (9%). Fifty-three percent of the peri-chemotherapy supportive care medications were potentially inappropriate. The number and categorization of the inappropriateness of the peri-chemotherapy supportive care medications as per the Beers criteria are provided in [Table 2].
|Table 2: The peri-chemotherapy supportive care medications that were considered potentially inappropriate as per the Beers criteria in our cohort of older Indian patients with cancer, along with the category of inappropriateness and the reasons why the medicines should be avoided|
Click here to view
| Discussion|| |
In our cohort of older Indian patients with cancer, we found that polypharmacy was present in 55% and excessive polypharmacy in 13%. Patients with lung cancer were at a significantly higher risk of polypharmacy. Unindicated medications such as vitamins and calcium were being taken by 20% of the patients and alternative medications (ayurvedic/homeopathic) by 23%. In 80% of the patients, at least one prescribed medication was potentially inappropriate, commonly PPI and tramadol. Considering the peri-chemotherapy supportive care medications, 53% were potentially inappropriate, commonly intravenous antihistamines, histamine H2 blockers, and steroids. This extensive use of PIMs raises important questions regarding the safe medication prescription practices in older Indian patients with cancer.
The prevalence of polypharmacy and the use of PIMs has varied in the literature. Karuturi et al. from the MD Anderson Cancer Center in the USA reported that 28% of the patients with breast cancer and 25% with colorectal cancer were on a PIM at baseline. In a prospective observational study in Korea by Hong et al., polypharmacy was present in 45% of the patients, excessive polypharmacy in 9%, and PIM use in 46%. Leger et al. from France reported that the prevalence of polypharmacy and PIM use was 75% and 34%, respectively. Various other authors have reported the prevalence rates of polypharmacy to be between 11% and 96%. Studies done in non-oncology Indian patients have reported that the prevalence of polypharmacy ranged from 66% to 88%, and PIM use from 31% to 66% of the patients.,,,, However, there are very limited data on the prevalence of polypharmacy and PIM use in older Indian patients with cancer. Recently, Banerjee et al. reported that 15% of the older Indian patients with cancer were on over five medications. The prevalence of polypharmacy in our cohort of patients was much higher at 55%. Important differences between our patients and those assessed by Banerjee et al. and variation in the definition of polypharmacy may explain the difference in the numbers. Palliative/supportive therapy was administered to 24% of the patients in Banerjee et al.'s study as compared to 58% of our patients. We defined polypharmacy as > 5 medications, while Banerjee et al. reported the number of patients who were on 3–5 medicines and >5 medicines. Banerjee et al. did not report the prevalence of PIM use in their patients; we found that four out of every five of our older Indian patients with cancer were on a PIM. This is an alarming statistic and raising awareness of the problem of polypharmacy, and PIM use would be the first step in attempting to tackle the issue.
Polypharmacy has been linked to several poor outcomes in older patients, including a higher symptom burden, worse quality of life, increased need for admission to the hospital or prolongation of the length of hospitalization, increased risk of readmission to the hospital, an increase in the non-cancer health events, adverse events, drug interactions, and higher overall treatment and health-care costs., Regarding cancer-related outcomes, in a cohort of patients with acute myeloid leukemia, patients in whom polypharmacy was identified were less likely to receive intensive chemotherapy and transplantation. The 1-year overall survival of patients with polypharmacy was lower at 29% versus 49% in the patients with no polypharmacy (P < 0.001). However, this decreased survival was driven by the cohort of patients who were younger than 60 years old; in these younger patients, those with polypharmacy had a 1-year OS of 37% vs. 65% in those without polypharmacy (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.21–3.15), while in patients ≥60 years, there was no difference in survival noted (26% vs. 27% at 1 year; HR, 1.12; 95% CI, 0.81–1.57). Other studies have not shown an association between the presence of polypharmacy and toxicity,, response rates, or outcomes. It is unclear whether the relationship of polypharmacy and PIM use with poor outcomes is causative or merely correlative, i.e., whether polypharmacy, which is a factor associated with PIM use,, merely acts as a marker for a sicker patient, who therefore requires more medications, and has a poorer outcome.
We found that 53% of the peri-chemotherapy supportive care medications were potentially inappropriate. The most commonly prescribed peri-chemotherapy supportive care PIMs were antihistamines (pheniramine and promethazine), H2-receptor blockers, and dexamethasone. Zhou et al. had found that 45% of the chemotherapy regimen templates in the National Comprehensive Cancer Network for hematologic malignancies included one or more PIMs, commonly first-generation antihistamines, corticosteroids, and H2-receptor antagonists. These peri-chemotherapy supportive care regimens have been developed in a younger cohort of patients, and it is unclear whether these medications are actually needed in older patients with cancer to diminish the risk of allergy, emesis, etc., and are therefore appropriate or whether they lead to more toxicities in older persons and are potentially inappropriate.
The main limitation of our study is the fact that we have only described the prevalence of polypharmacy and PIM use and have not evaluated whether these have any association with outcomes such as chemotherapy toxicity or survival. Our goal was to raise awareness of the scope of the problem, and to induce us to think about safe prescription practices while caring for older patients with cancer. The next step would be to study the relationship of polypharmacy and PIM use with outcomes in our older Indian patients with cancer and to determine the optimal peri-chemotherapy supportive care medication regimen. Although we provided the information regarding the presence of polypharmacy and PIM use to the treating physician, with advice regarding change to more appropriate medications, we do not have the information as to whether the substitution of medication occurred. Involvement of a clinical pharmacologist and evaluation of patients by a multidisciplinary geriatric oncology team may help promote safer prescription practices in older adults with cancer.
| Conclusions|| |
Polypharmacy and the use of PIMs are prevalent in older Indian patients with cancer. Over half of the patients receive at least one PIM as part of the peri-chemotherapy supportive care regimen. Understanding the problem, discontinuing unindicated medications, and substituting less toxic more age-appropriate medications are important steps to ensure safe medication prescription practices in older patients with cancer.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Morin L, Johnell K, Laroche ML, Fastbom J, Wastesson JW. The epidemiology of polypharmacy in older adults: Register-based prospective cohort study. Clin Epidemiol 2018;10:289-98.
Hamilton H, Gallagher P, Ryan C, Byrne S, O'Mahony D. Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients. Arch Intern Med 2011;171:1013-9.
Beers MH, Ouslander JG, Rollingher I, Reuben DB, Brooks J, Beck JC. Explicit criteria for determining inappropriate medication use in nursing home residents. UCLA division of Geriatric Medicine. Arch Intern Med 1991;151:1825-32.
By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;67:674-94.
Noronha V, Ramaswamy A, Dhekle R, Talreja V, Gota V, Gawit K, et al
. Initial experience of a geriatric oncology clinic in a tertiary cancer center in India. Cancer Res Stat Treat 2020;3:208-17. [Full text]
Karuturi MS, Holmes HM, Lei X, Johnson M, Barcenas CH, Cantor SB, et al
. Potentially inappropriate medication use in older patients with breast and colorectal cancer. Cancer 2018;124:3000-7.
Hong S, Lee JH, Chun EK, Kim KI, Kim JW, Kim SH, et al
. Polypharmacy, inappropriate medication use, and drug interactions in older korean patients with cancer receiving first-line palliative chemotherapy. Oncologist 2020;25:e502-11.
Leger DY, Moreau S, Signol N, Fargeas JB, Picat MA, Penot A, et al
. Polypharmacy, potentially inappropriate medications and drug-drug interactions in geriatric patients with hematologic malignancy: Observational single-center study of 122 patients. J Geriatr Oncol 2018;9:60-7.
Sharma M, Loh KP, Nightingale G, Mohile SG, Holmes HM. Polypharmacy and potentially inappropriate medication use in geriatric oncology. J Geriatr Oncol 2016;7:346-53.
Rakesh KB, Chowta MN, Shenoy AK, Shastry R, Pai SB. Evaluation of polypharmacy and appropriateness of prescription in geriatric patients: A cross-sectional study at a tertiary care hospital. Indian J Pharmacol 2017;49:16-20.
] [Full text]
Subeesh VK, Gouri N, Beulah TE, Shivashankar V. A prospective observational study on polypharmacy in geriatrics at a private corporate hospital. J App Pharm Sci 2017;7:162-7.
Ramanath K, Nedumballi S. Assessment of medication-related problems in geriatric patients of a rural tertiary care hospital. J Young Pharm 2012;4:273-8.
Maheshkumar VP, Dhanapal CK. Prevalence of polypharmacy in geriatric patients in rural teaching hospital. Am J Phytomed Clin Ther 2014;2:413-9.
Narvekar RS, Bhandare NN, Gouveia JJ, Bhandare PN. Utilization pattern of potentially inappropriate medications in geriatric patients in a tertiary care hospital: A retrospective observational study. J Clin Diagn Res 2017;11:FC04-8.
Banerjee J, Behal P, Satapathy S, Kandel R, Upadhyay AD, Dwivedi S, et al
. Implementing and validating a care protocol for older adults with cancer in resource limited settings with a newly developed screening tool. J Geriatr Oncol 2021;12:139-45.
Schenker Y, Park SY, Jeong K, Pruskowski J, Kavalieratos D, Resick J, et al
. Associations between polypharmacy, symptom burden, and quality of life in patients with advanced, life-limiting illness. J Gen Intern Med 2019;34:559-66.
Park JW, Roh JL, Lee SW, Kim SB, Choi SH, Nam SY, et al
. Effect of polypharmacy and potentially inappropriate medications on treatment and posttreatment courses in elderly patients with head and neck cancer. J Cancer Res Clin Oncol 2016;142:1031-40.
Sehgal V, Bajwa SJ, Sehgal R, Bajaj A, Khaira U, Kresse V. Polypharmacy and potentially inappropriate medication use as the precipitating factor in readmissions to the hospital. J Family Med Prim Care 2013;2:194-9.
] [Full text]
Hamaker ME, Seynaeve C, Wymenga AN, van Tinteren H, Nortier JW, Maartense E, et al
. Baseline comprehensive geriatric assessment is associated with toxicity and survival in elderly metastatic breast cancer patients receiving single-agent chemotherapy: Results from the OMEGA study of the Dutch breast cancer trialists' group. Breast 2014;23:81-7.
Balducci L, Goetz-Parten D, Steinman MA. Polypharmacy and the management of the older cancer patient. Ann Oncol 2013;24 Suppl 7:vii36-40.
Shrestha S, Shrestha S, Khanal S. Polypharmacy in elderly cancer patients: Challenges and the way clinical pharmacists can contribute in resource-limited settings. Aging Med (Milton) 2019;2:42-9.
Dhakal P, Lyden E, Muir KE, Al-Kadhimi ZS, Koll T, Maness LJ, et al
. Prevalence and effects of polypharmacy on overall survival in acute myeloid leukemia. Leuk Lymphoma 2020;61:1702-8.
Iurlo A, Nobili A, Latagliata R, Bucelli C, Castagnetti F, Breccia M, et al
. Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: Effects on response rate, toxicity and outcome. Oncotarget 2016;7:80083-90.
Alkan A, Yaşar A, Karcı E, Köksoy EB, Ürün M, Şenler FÇ, et al
. Severe drug interactions and potentially inappropriate medication usage in elderly cancer patients. Support Care Cancer 2017;25:229-36.
Reis CM, Dos Santos AG, de Jesus Souza P, Reis AM. Factors associated with the use of potentially inappropriate medications by older adults with cancer. J Geriatr Oncol 2017;8:303-7.
Zhou A, Holmes HM, Hurria A, Wildes TM. An analysis of the inclusion of medications considered potentially inappropriate in older adults in chemotherapy templates for hematologic malignancies: One recommendation for all? Drugs Aging 2018;35:459-65.
[Figure 1], [Figure 2]
[Table 1], [Table 2]