In a single-center phase II study reported in The Lancet Oncology, Teply et al found that bipolar androgen therapy can induce prostate-specific antigen (PSA) response and resensitization to enzalutamide (Xtandi) in men with metastatic castration-resistant prostate cancer who progressed on enzalutamide.
The study included 30 asymptomatic patients treated at Johns Hopkins University with bipolar androgen therapy consisting of intramuscular testosterone cipionate 400 mg every 28 days until progression and continued luteinizing hormone-releasing hormone agonist therapy. Patients could have received no more than two previous second-line hormonal therapies and had to have progression on enzalutamide with a continued PSA rise after treatment discontinuation. After post–bipolar androgen therapy progression, patients were rechallenged with enzalutamide 160 mg daily. The co-primary endpoints were 50% decline in PSA concentration from baseline (PSA50) after bipolar androgen therapy and after enzalutamide rechallenge on intent-to-treat analysis.
PSA50 response was observed in 9 (30%) of the 30 patients; median PSA progression-free survival was 3.3 months. In total, 21 of 29 patients completing bipolar androgen therapy underwent enzalutamide rechallenge. On intent-to-treat analysis, PSA50 response was achieved on enzalutamide rechallenge in 15 (52%) of 29 patients. Median PSA progression-free survival among all patients undergoing enzalutamide rechallenge was 5.5 months.
The only grade 3 or 4 adverse event occurring in more than one patient during bipolar androgen therapy was hypertension (n = 3, 10%), with other events consisting of pulmonary embolism, myocardial infarction, urinary obstruction, gallstone, and sepsis. No grade 3 or 4 adverse events occurred in more than one patient during enzalutamide rechallenge. No treatment-related deaths were observed.
The investigators concluded, “[Bipolar androgen therapy] is a safe therapy that resulted in responses in asymptomatic men with metastatic castration-resistant prostate cancer and also resensitisation to enzalutamide in most patients undergoing rechallenge. Further studies with [bipolar androgen therapy] are needed to define the potential clinical role for [bipolar androgen therapy] in the management of metastatic castration-resistant prostate cancer and the optimal strategy for sequencing between androgen and antiandrogen therapies in metastatic castration-resistant prostate cancer to maximise therapeutic benefit to patients.”
The study was funded by the National Institutes of Health and National Cancer Institute.
Samuel R. Denmeade, MD, of Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, is the corresponding author for The Lancet Oncology article.
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