Phase II Trial of Bipolar Androgen Therapy (BAT) With Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC) On Enzalutamide (Xtandi)

One of the common adaptive resistance mechanisms in metastatic castrate resistant prostate cancer (mCRPC) is the over expression of the androgen receptor (AR). There is a theory that high dose testosterone (BAT) may induce tumor responses and restore normal AR expression allowing for the re-introduction of drugs that have developed a treatment resistance.

To evaluate BAT, researchers assessed men with mCRPC that was progressing while the men were on enzalutamide (Xtandi).  They evaluated their responses to BAT and if the resistance to Xtandi would be reversed after BAT. 

The subject men were minimally symptomatic and had mCRPC coupled with progression on Xtandi. The men received high doses of testosterone cypionate (400mg IM every 28d) while continued gonadal suppression (LHRH therapy with drugs like Lupron unless they had had an orchiectomy) until they had disease progression.

The men were evaluated with PSA tests each cycle, and CT/bone scans every 3 cycles. When the men showed progression on BAT, they were re-challenged (put back on) Xtandi (160 mg daily).

The trial included 30 men.  The researchers found that there were no dose-limiting toxicities from the testosterone.  Two men had transient pain flares after BAT was started. The common grade 1-2 adverse events experienced were musculoskeletal pain (40%), increased hemoglobin levels (37%), breast tenderness (17%) and rash (17%). Grade 3-4 adverse events that were potentially attributable to the BAT therapy occurred were pulmonary embolism, NSTEMI, and urinary obstruction.

The researchers concluded that BAT in some men with progressive mCRPC after Xtandi is effective. They also concluded that BAT is a safe therapy which provided positive responses in men with mCRPC who were asymptomatic and that after BAT some men were able to go back on (re-challenged) Xtandi with a positive effect. 

There is another trial that is still on-going comparing BAT to Xtandi in mCRPC.

 Clinical trial information: NCT02090114.

Joel T. Nowak, MA, MSW wrote this Post.  Joel is the CEO/Executive Director of Cancer ABCs.  He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.