Hormonal therapies for advanced prostate cancer linked to a higher risk of falls and fractures – Harvard Health Blog
Falls are one of the leading causes of death and injury in older people, and the risk increases dramatically in older people being treated for cancer. Now, researchers are reporting that a new class of drugs for advanced prostate cancer is associated with a significant increased risk of falls.
Called androgen receptor inhibitors, or ARIs, these drugs target testosterone, a hormone that accelerates the growth of prostate tumors. Unlike traditional hormone treatments that interfere with the body’s ability to produce testosterone (known as androgen deprivation therapy or ADT), ARIs work by preventing testosterone from binding to its receptor on cancer cells. Three ARIs were evaluated in the study – apalutamide, enzalutamide and darolutamide – and each may limit the progression of prostate cancer and prolong survival. The researchers pointed out that the benefits of using ARI outweighs the risk of falls and fractures, which are rare even in treated patients.
What the investigators did
To generate the results, the researchers performed a systematic review of previously published studies comparing ARI treatments with a placebo. A total of 11 studies involving a combined total of 11,382 men met the endpoint. The average age of the men was 72 years and ARI treatments lasted between 5.4 and 20.5 months. Men were excluded if they had a history of heart disease or seizures.
What they found
Results showed that 525 of 6,536 men treated with ARI (8%) experienced falls, compared with 221 of 4,846 men (5%) who received placebo. About half of the falls in both groups resulted in fractures. However, grade 3 fractures causing more serious injury occurred 1.6 times more frequently in men taking ARIs. Apalutamide was associated with the highest risk of falls (12%), followed by 8% enzalutamide and 4.2% darolutamide.
It is not clear exactly why ARIs increase the risk of falls. Apalutamide and enzalutamide both cross the blood-brain barrier (which makes them useful for treating brain metastases) and therefore may have more side effects on the central nervous system, including falls. Medicines can weaken men by reducing the mass and strength of skeletal muscles. Concomitant use of other medicines, such as benzodiazepines (including valium) or opioids, may also increase the risk.
To prevent falls in older men, investigators recommended risk screening tools more commonly used in non-cancer populations. They chose the Hendrich II fall risk model, which predicts falls based on independent risk factors such as depression, bladder and bowel disorders, dizziness, use or discontinuation of antiepileptic drugs, treatment with benzodiazepines and poor performance on an “up-and-go” test of sitting uphill. Men who score high on a screening assessment will need precautionary interventions. It is possible that some bone health drugs such as denosumab may protect against fractures, but data on these types of agents in advanced prostate cancer are limited, so investigators could not make any findings. strong recommendation one way or the other.
“I welcome this study because it draws attention to an often overlooked problem in older men, many of whom may be frail and have lost bone density and bone mass due to the drop in testosterone values resulting from holistic treatment, ”said Dr. Marc Garnick, Gorman Brothers professor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, editor-in-chief of Harvard Health Publishing Annual report on prostate diseases, and editor of HarvardProstateKnowledge.org. “Falls and traumatic fractures are a devastating event for this patient population and studies like this are long overdue. Hopefully, with studies like this and more data collected, best fall prevention practices will be developed and implemented at the point of care.
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