After Disease Progression on Enzalutamide, Can Bipolar Androgen Therapy Make a Difference in Prostate Cancer?
Posted: Thursday, June 28, 2018
A Johns Hopkins University team studied 30 asymptomatic patients with metastatic castration-resistant prostate cancer whose disease had progressed on and after enzalutamide to see whether bipolar androgen therapy would significantly decrease their prostate-specific antigen (PSA) levels. The Baltimore researchers wrote: “Bipolar androgen therapy…resulted in responses…and also [in] resensitisation to enzalutamide in most patients undergoing rechallenge.” They deemed the therapy “safe” based on the rate and types of adverse events. The corresponding author of the study, published in The Lancet Oncology, is Samuel R. Denmeade, MD, of Hopkins’ Sidney Kimmel Comprehensive Cancer Center.
In this open-label phase II trial, bipolar androgen therapy consisted of intramuscular testosterone cipionate at 400 mg every 28 days until disease progression and continued luteinizing hormone-releasing hormone agonist therapy. Upon disease progression after bipolar androgen therapy, patients were rechallenged with oral enzalutamide at 160 mg daily.
Of the 30 patients, 9 achieved an investigator-assessed 50% decline in PSA (PSA50) concentration from baseline with bipolar androgen therapy, which was one of the two primary endpoints (P < .0001). A total of 29 patients completed bipolar androgen therapy , and 21 then continued to the enzalutamide rechallenge. Of the rechallenged patients, 15 achieved a PSA50 response, meeting the second primary endpoint (P < .0001; based on intention-to-treat analysis).
“Further studies…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,” concluded the authors.