This article is more than 5 years old. Information may no longer be current.
Hormonal drugs for prostate cancer increase risk, incidence of cardiovascular events
Click Here to Manage Email Alerts
Patients who received hormonal regimens for the treatment of castration-resistant prostate cancer experienced a significant increase in incidence of and relative risk for cardiovascular toxicity, according to results of a meta-analysis.
Roberto Iacovelli, MD, medical oncologist in the division of urogenital and head and neck tumors at European Institute of Oncology in Milan, and colleagues sought to define the incidence and RR of cardiovascular events in a population of patients treated with new hormonal therapies for metastatic castration-resistant prostate cancer.
Incidence of all-grade toxicities (grades 1-4) and high-grade toxicities (grade 3-4) served as the primary outcome of the study.
Iacovelli and colleagues identified six prospective phase 2 or phase 3 studies that included a total of 7,830 patients. Within each study, researchers considered treatment with a novel hormonal agent plus prednisone in the experimental arm (n = 4,520) and placebo plus prednisone (n = 3,310) as the control.
Patients in those studies received the hormonal agents abiraterone (Zytiga, Janssen), enzalutamide (Xtandi, Astellas) or orteronel.
Using data from five of the studies (n = 6,375) to evaluate cardiac toxicity, the researchers observed an increased risk for cardiac toxicity with hormonal agents across all grades (RR = 1.32, 95% CI, 1.08-1.6) compared with placebo. The incidence of any-grade cardiac toxicity in the experimental arms was 14.8% vs. 11.5% for the placebo arms, which the researchers noted equated to a small absolute difference.
There was no increased risk for grade 3 to grade 4 events (RR = 1.35; 95% CI, 0.90-2.03).
Researchers used data from all six studies when evaluating the risk for or incidence of hypertension. Again, the researchers found an increased risk associated with hormonal therapy for hypertension of all grades (RR = 1.84; 95% CI, 1.37-2.46), as well as an increased risk for grade 3 to grade 4 events (RR = 1.77; 95% CI, 1.13-2.77) compared with placebo.
More patients who received hormonal therapies experienced any-grade hypertension (absolute incidence, 12.5% vs. 7.5%) and grade 3 to grade 4 hypertension (3.7% vs. 2.4%).
“We found that such new hormonal therapies significantly increased the risk for both all- and high-grade hypertension, but this was more evident in patients treated with enzalutamide,” Iacovelli and colleagues wrote.
The researchers noted it was unclear how the use of steroids, particularly in patients treated with CYP-17 inhibitors (abiraterone and orteronel), might elevate the incidence of cardiovascular toxicity.
Additionally, the researchers noted the findings were based on trial results rather than individual patient data and, when sub-analyzed, results were affected by the number of studies included and indirect comparisons. Also, trials used different versions of the Common Terminology Criteria for Adverse Events.
“Despite these limitations … even if high-grade events are not as frequent, they may nevertheless affect patient survival and quality of life, especially in those who received new hormonal therapies prior to docetaxel because of an expected median survival greater than 2.5 years,” the researchers wrote. “We suggest investigating patients for existing risk factors in order to optimize those who are modifiable, and carefully following them up for the onset of new treatment-related cardiovascular events.” – by Anthony SanFilippo
Disclosure: The researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts