ADT May Cause Cardiac Toxicity, But Unanswered Questions Remain

The use of androgen deprivation therapy (ADT) to treat prostate cancer comes with a list of adverse events (AEs) for nurses to look out for, ranging from hot flashes to cognitive impairment, muscle wasting, and anemia. Researchers and advocates in the field are now trying to spread awareness about another potential AE from this therapy — cardiac complications – though the jury may still be out when it comes to the hard science behind them.

“If you look at all the trials, they’re rather confusing. Most of the data are from observational and retrospective studies suggesting that there potentially could be a link,” Pei-Chun McGregor, MD, said in an interview with OncLive, a sister publication of Oncology Nursing News.

ADT’s Role in Prostate Cancer: What We Know

ADT is a key treatment modality for many men diagnosed with prostate cancer. It works by suppressing the testosterone that makes the disease grow. However, while ADT is efficacious, like other cancer treatments, it is not without its own set of AEs. McGregor described ADT as something that leads to “chemically-induced menopause” for men.

“That means [patients experience] all of the great things that come with menopause, which includes loss of libido,” she said. “Unfortunately for men, [this means] erectile dysfunction, hot flashes — many patients will experience that – muscle wasting, development of subcutaneous fat, anemia, fatigue, and cognitive impairment.”

Potential Link to Cardiac Complication: Spreading the Word

As McGregor mentioned, there are a few retrospective, observational studies that examined the potential correlation between ADT treatment and cardiac toxicities. For example, a trial of veterans included more than 37,000 men and showed that patients in the GnRH agonist — a common type of ADT – group had significant effects on their cardiovascular system, including increased rates of heart attacks, strokes, and sudden cardiac deaths.

Healthcare providers treating men on ADT should be aware of this potential correlation.

“If you talk to most internists, they would not know that ADT can cause adverse changes metabolically, and they might not be checking lipids or blood pressure.” McGregor said.

“Even for cardiologists, many of us don’t know, and some of the medications that are used to block testosterone have also been shown to increase their QT; if QT is increased, then [the patients] are at risk for arrhythmias, which means they can potentially die from an abnormal heart rhythm.”

Guidelines are currently being worked on that will hopefully make healthcare practitioners more aware of this AE, McGregor said, emphasizing that a team-based approach will become more important in caring for these patients.

“The whole field of medicine is really approaching a more multidisciplinary kind of care,” she said. “It’s no longer, ‘I’m in my own little box. I’m a heart doctor, I only look at the heart and that’s it.’ We really need to treat the patient wholly.”

Unanswered Questions and Next Steps

Upcoming studies such as the phase IIb PRONOUNCE trial are looking to address the potential correlation.

PRONOUNCE is a multicenter, randomized, controlled trial looking at cardiovascular events in patients with prostate cancer and also with underlying pre-existing cardiac disease. Participants will be randomized into 2 arms: the GnRH antagonist arm (degarelix [Firmagon]) and the agonist arm (leuprolide). The primary endpoint is time from randomization to the first major adverse cardiovascular event (MACE). Researchers are also looking at individual MACE endpoints.

“Very interestingly, from this trial, they are also looking at biomarkers — cardiovascular, inflammatory, and immune biomarkers – so that will be very telling,” McGregor said. “It’s the first trial to prospectively study this, so we’ll finally learn whether GnRH agonists have that potentially adverse signal toward the cardiovascular system over antagonists. It will be very exciting.”

And while McGregor is hopeful that the PRONOUNCE trial will offer much insight into the issue, there are still unanswered questions that will remain, such as whether or not there are drug-drug interactions for patients being given multiple agents to treat their prostate cancer.

“There’s a whole lot that we still don’t know, unfortunately,” McGregor said.

Read more:

Expert Looks Ahead in Prostate Cancer Treatment

Cancer Survivors, Spouses Affected by Cardiovascular Disease at Varying Rates

A version of this article was originally published on OncLive as, “ADT-Associated Cardiac AEs in Prostate Cancer Require Multidisciplinary Care.”