Polypharmacy decreases the survival probability of older colorectal cancer patients


Colorectal cancer (CRC) is the fourth most frequently diagnosed type of cancer and a major worldwide public health concern. Despite the efforts in the development of modern therapeutic strategies, the prognosis of CRC mostly depends on the disease stage, and specific biological features. In 2020, 1.93 million new cases of CRC were diagnosed, and it was responsible for 916 000 confirmed deaths. CRC is more likely to be diagnosed in older adults, with more than half of those diagnosed above 70. Fortunately, treatment of CRC is improving, and now a 5-year survival rate has surpassed 60%.

Since CRC is more likely to be diagnosed in older adults, it also means that these are individuals living with multiple co-morbidities. These are individuals already taking several medications. Once diagnosed with cancer, they often also need to undergo chemotherapy and take medicines to alleviate the side effects of the chemotherapy. It means that most of these individuals end up taking many medications daily. German Cancer Research Center scientists Li-Ju Chen and Ben Schöttker hypothesized that taking too many medications (polypharmacy) might have its downsides. Thus, there is a need to find to what degree a prescription of too many medications to CRC patients is significantly associated with the 5-year survival probability.

Polypharmacy is usually defined as the concomitant use of 5 or more drugs by a single individual. It often reflects the coexistence of various health problems, including chronic diseases (eg, diabetes and heart failure), acute conditions (eg, infections), and symptoms (eg, pain), which accumulate with age. Polypharmacy increases the risk of adverse drug-related events in older adults. The researchers used a slightly modified polypharmacy definition by not counting pharmaceutically irrelevant drugs, such as vitamin products, and counting the number of active ingredients and not of pills. For example, two active ingredients against high blood pressure in one pill were counted as two medications. They further defined excessive polypharmacy as those taking eight or more drugs. The cohort study included 3,239 patients older than 65 years of age recruited between 2003 and 2016 across 22 hospitals in Germany at the time of the colorectal cancer surgery.

The authors’ findings showed that polypharmacy was identified in approximately half of the patients studied. Additionally, they found that almost a quarter of the patients investigated had excessive polypharmacy. Interestingly, the study found that male patients were at much lower risk of being under the polypharmacy category. Furthermore, polypharmacy prevalence increased with age, which is expected due to the rise of comorbidities with higher age. Generally, polypharmacy was associated with conditions like hypertension, various cardiovascular disorders, history of myocardial infarction or stroke, atrial fibrillation, chronic pain, depression, and hypothyroidism.

During the follow-up period of 5 years, 1070 patients died. Among them, 615 deaths or 57% were due to CRC, and 296 deaths or 28% had causes of death other than cancer. The research team found a weak association between polypharmacy and mortality due to CRC. In contrast, they found a stronger association of polypharmacy with non-cancer mortality. However, when they corrected the analyses for the influence of comorbidities on the results, this gap closed, and the risk of polypharmacy for CRC-related death was increased by 31%, whereas the risk for non-cancer-related death was comparably increased by 22%. They also noticed that this increased risk of death did not appear if the number of medications was up to 7, but with 8 or more drugs it increased significantly.

In a nutshell, the German study concluded that polypharmacy might increase the risk of death within the first 5 years after CRC diagnosis. Of note, this increased risk is insignificant in those prescribed up to seven medications. However, the increased risk became statistically significant in the case of excessive polypharmacy, which was defined as concomitant use of 8 or more medications. Thus, the researchers suggest that doctors should review the prescriptions of older patients living with CRC and perhaps deprescribe some of the less essential drugs if that is possible, particularly if the patient is taking eight or more drugs. The authors’ findings in the new study can increase awareness about the unique challenges of older patients with CRC and polypharmacy. Randomized controlled trials are needed that test the emerged hypothesis that reducing the medication number of CRC patients with excessive polypharmacy actually increases their survival probability.

Polypharmacy decreases the survival probability of older colorectal cancer patients - Medicine Innovates

About the author

Ben Schöttker

After studying pharmacy and public health, he did his PhD at the University of Lübeck, Germany. Since 2009 he is working as a scientist in the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center in Heidelberg, Germany. Besides work on biomarkers useful in ageing research, Ben Schöttker’s work has a focus on drug safety and effectiveness in older adults.

About the author

Li-Ju Chen

After receiving her bachelor’s degree in pharmacy in 2012 and master’s degree in clinical pharmacy in 2014 from National Taiwan University in Taipei, Taiwan, Li-Ju Chen has practiced as a pharmacist in National Taiwan University Hospital for about 3 years. Later on, she has worked as a research assistant and a research associate in the Health Data Research Center at National Taiwan University. In 2019, Li-Ju Chen started her Ph.D. under supervision of Dr. Ben Schöttker in the Division of Clinical Epidemiology and Aging Research (Division Head: Prof. Hermann Brenner) at German Cancer Research Center in Heidelberg, Germany. She recently completed her Ph.D. dissertation, in which she mainly investigated the associations of polypharmacy and co-medication quality (as assessed by the Fit for The Aged list) with survival outcomes and chemotherapy-related adverse drug reactions in a large cohort of older colorectal cancer (CRC) patients. Furthermore, she also investigated the roles of functional status, Charlson comorbidity index, frailty index, polypharmacy, and co-medication quality in the prediction of CRC survival.


Chen, L.-J., Nguyen, T. N. M., Chang-Claude, J., Hoffmeister, M., Brenner, H., & Schöttker, B. (2021). Association of Polypharmacy with Colorectal Cancer Survival Among Older Patients. The Oncologist, 26(12), e2170–e2180. https://doi.org/10.1002/onco.13961.

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