Hormonal therapies for advanced prostate cancer linked to a higher risk of falls and fractures – . Health Blog

Falls are one of the leading causes of death and injury in the elderly, and the risk increases significantly in older people being treated for cancer. Now researchers are reporting that a newer class of drugs for advanced prostate cancer has been linked to a significant increase in the risk of falls.

These drugs, called androgen receptor inhibitors, or ARIs, target testosterone, a hormone that speeds up the growth of prostate tumors. Unlike traditional hormonal treatments that affect the body's ability to make testosterone (known as androgen deprivation therapy, or ADT), ARIs prevent testosterone from binding to its receptor on cancer cells. The study evaluated three ARIs – apalutamide, enzalutamide, and darolutamide – and each can limit prostate cancer progression and extend survival. The researchers emphasized that the benefits of using ARIs outweigh the risk of falls and fractures, which are rare even in treated patients.

What the investigators did

To generate the results, the researchers conducted a systematic review of previously published studies that compared ARI treatments to placebo. A total of 11 studies with a total of 11,382 men met the evaluation criteria. The mean 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 seizure disorders.

What they found

The results showed that 525 of 6,536 ARI-treated men (8%) had suffered falls compared to 221 of 4,846 men (5%) who were given a placebo. About half of the falls in both groups resulted in fractures. However, degree 3 fractures that caused more severe injuries were 1.6 times more likely to occur in men taking ARIs. Apalutamide was associated with the highest risk of falls (12%), followed by enzalutamide with 8% and darolutamide with 4.2%.

Why ARIs increase the risk of falls is not known. Apalutamide and enzalutamide both cross the blood-brain barrier (which makes them useful for treating brain metastases) and, therefore, can have more severe central nervous system side effects, including falls. The drugs can weaken men by decreasing skeletal muscle mass and strength. Concomitant use of other drugs such as benzodiazepines (including Valium) or opioids can also increase the risk.

To help prevent falls in older men, investigators recommended risk screening tools that are more commonly used in non-cancer populations. They selected the Hendrich II fall risk model, which predicts falls based on independent risk factors including depression, impaired bladder and bowel function, dizziness, use or withdrawal of anti-epileptic drugs, treatment with benzodiazepines, and poor performance on a "get-up-and." -Go test of standing up from a sitting position. Men who score high on a screening assessment must take precautionary measures. It is possible that certain bone health drugs like denosumab can protect against fractures. However, data on these drugs in advanced prostate cancer are limited, so there is no way the researchers can make a strong recommendation.

"I applaud this study as it highlights an often overlooked problem in older men, many of whom are frail and have lost bone density and mass due to lower testosterone levels as a result of overall treatment," said Dr. Marc Garnick, Professor of Medicine with the Gorman Brothers at . Medical School and Beth Israel Deaconess Medical Center, Editor of the . Health Publishing Annual Report on Prostate Diseases and Editor-in-Chief of HarvardProstateKnowledge.org. “Falls and traumatic fractures are a devastating event for this patient population, and studies like this are long overdue. Hopefully, as studies like this one come to light and more data is collected, best practices for fall prevention at the point of care will be developed and implemented. "