Several years ago, Samuel Denmeade, M.D., Director of the Division of Genitourinary Oncology at the Sidney Kimmel Comprehensive Cancer Center, and colleagues came up with a new concept for treating advanced prostate cancer that seemed counterintuitive: they gave a patient testosterone, lots of it. And then they took it away with androgen deprivation therapy (ADT). And then they gave high-dose testosterone again. And then more ADT.
They called this alternating approach “Bipolar Androgen Therapy” (BAT) because it cycles between polar extremes of very high and very low male hormones. “The idea,” Denmeade explains, “is to mess up the cancer cell’s ability to adapt.” Paradoxically, although low levels of testosterone can make prostate cancer cells grow, “at high doses, the cancer cells don’t grow as well, or they die.”
Denmeade and colleagues within the Prostate Cancer Research Program are testing BAT in several clinical trials:
The ACROBAT study is testing the rapid cycling of an oral form of testosterone in men whose cancer has just progressed to the castrate-resistant state (CRPC).
The STEP-UP study is evaluating the effectiveness of repeatedly alternating BAT and enzalutamide in men with CRPC cancer who have progressed on abiraterone.
The BATRAD study is testing whether the effectiveness of the bone metastases-targeting drug 223- Radium (Xofigo) can be enhanced when given in combination with BAT. This study is being performed in collaboration with Pedro Isaacsson Velho, M.D., in Porto Alegre, Brazil.
Recently, medical oncologist Mark Markowski, M.D., Ph.D., led the COMBAT study, which tested the effect of BAT in combination with immunotherapy. In another recent study, published in the Journal of Clinical Investigation, medical oncologist Laura Sena, M.D., Ph.D., and colleagues demonstrated that BAT has profound effects on the metabolism of CRPC cells. “Based on this work,” says Denmeade, “she has developed the innovative APEX clinical trial that combines BAT with DFMO, an oral drug that can block the production of key metabolites required for prostate cancer cell growth and survival.” This trial is open for patient accrual. For more information about these trials, please call 410-614-6337.
