Novel prostate cancer therapy may have dangerous side effect

In a new study, researchers found novel oral androgen signaling inhibitor therapies are linked to a higher risk of death in men with heart problems.

The research was conducted by a team from the Sidney Kimmel Cancer Center – Jefferson Health.

Men with advanced prostate cancer that progressed on androgen deprivation therapy (ADT) are typically treated with novel androgen signaling inhibitor therapies such as abiraterone acetate and enzalutamide.

Previous research has shown there is a small but significant increase in the risk of cardiovascular toxicity in men treated with ADT.

However, little was known about the short-term mortality in men with heart problems treated with these novel oral androgen signaling inhibitor therapies.

In the study, the team examined data from 3,876 patients with advanced prostate cancer.

About 67% of the men treated with abiraterone acetate or enzalutamide had at least one pre-existing heart condition (such as congestive heart failure, acute myocardial infarction, stroke, atrial fibrillation, and ischemic heart disease) in addition to prostate cancer.

The team found higher mortality after starting ADT in these patients.

The team then examined the outcomes by chemotherapy use, since patients whose cancers no longer respond to chemotherapy tend to have more advanced disease and shorter life expectancy than those who have not been on chemotherapy.

They found that compared to patients receiving the same therapy for prostate cancer without pre-existing heart conditions, those with at least three heart conditions had a 43% increase in the relative risk of 6-month mortality (if they had chemotherapy before using the oral androgen signaling inhibitor therapy) and a 56% increase in the relative risk of 6-month mortality among patients without documented chemotherapy use.

In essence, having three or more pre-existing heart conditions was linked to roughly a 50% increase in mortality.

In addition, the researchers examined changes in hospitalization rates following the use of the two oral androgen inhibitors.

Among the no-chemotherapy group, abiraterone acetate is linked to an increase in post-treatment hospitalization but the same pattern was not observed in enzalutamide patients.

Among patients with at least three pre-existing heart conditions and no history of chemotherapy, enzalutamide is linked to a 41% lower post-treatment hospitalization rate compared to abiraterone acetate.

The researchers found that abiraterone acetate is linked to increased hospitalizations in patients taking various classes of medications.

They say in addition to blocking androgen synthesis, abiraterone acetate may interact with many drugs and lead to a higher risk of toxicity from a wide range of other medications.

Further studies are warranted to understand the potential mechanisms underlying the observations.

The lead author of the study is Grace Lu-Yao, Ph.D., MPH, professor and vice-chair of medical oncology at Thomas Jefferson University.

The study is published in the journal European Urology.

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