Metastatic castration-resistant prostate cancer that progresses after enzalutamide treatment may be effectively managed with bipolar androgen therapy, according to recent research published in The LANCET Oncology (online December 13, 2017; doi:10.1016/S1470-2045(17)30906-3).
Prior research has shown that prostate cancer that progresses after enzalutamide treatment does not respond well to further anti-androgen therapy. However, there is belief that rapid cycling between high and low serum testosterone concentrations—termed bipolar androgen therapy—in this disease setting may induce tumor response.
Samuel R Denmeade, MD, department of oncology, Johns Hopkins University School of Medicine, and colleagues conducted a study aimed at evaluating bipolar androgen therapy in patients with metastatic castration-resistant prostate cancer that progressed after enzalutamide. The phase II, open-label study enrolled 30 patients aged 18 years or older who had histologically confirmed and radiographically documented metastatic castration-resistant prostate cancer, with no more than two previous second-line hormonal therapies, and a castration concentration of testosterone.
Patients received bipolar androgen therapy until progression, followed by rechallenged enzalutamide. Primary endpoints included investigator-assessed 50% decline in prostate-specific antigen (PSA) concentration from baseline for bipolar androgen therapy and for enzalutamide rechallenge.
Researchers reported that 29 of the patients completed bipolar androgen therapy and 21 patients proceeded to enzalutamide rechallenge. Among this population, 15 achieved a 50% decline in PSA concentration from baseline as a result of therapy.
The only grade 3/4 adverse event resulting from bipolar androgen therapy in more than one patient was hypertension (10%; n = 3). No grade 3/4 toxicities occurred in more than one patients during enzalutamide rechallenge.
Dr Denmeade and colleagues concluded that bipolar androgen therapy is a safe and produces responses in asymptomatic patients with metastatic castration-resistant prostate cancer while allowing for resensitization to enzalutamide in most patients undergoing rechallenge. Further studies with bipolar androgen therapy are needed to define the potential clinical role in managing this type of prostate cancer, they wrote.—Zachary Bessette