Bipolar Androgen Therapy Showing Promise for Castration Resistant Prostate Cancer
Bipolar androgen therapy may benefit some men with asymptomatic CRPC who have a low to moderate metastatic burden.
It sounds counterintuitive, but according research published earlier this year it may be possible to treat castration-resistant prostate cancer (CRPC) with high dose testosterone therapy.
In an article published in Science Translational Medicine, researchers at Johns Hopkins reported that bipolar androgen therapy (BAT) may benefit some men with asymptomatic CRPC who have a low to moderate metastatic burden.1
The researchers conducted a study in which they gave a group of asymptomatic men with CRPC three 28-day cycles of an intramuscular injection of testosterone and 2 weeks of etoposide.
Men who showed decreases in prostate-specific antigen (PSA) levels after three cycles were continued on testosterone injections alone.
BAT floods prostate cancer cells with testosterone at a critical juncture and so the cells are killed by the hormone shock. It is well known that all men with metastatic prostate cancer eventually develop resistance to primary castrating therapy and secondary androgen deprivation therapies (ADTs).
It is believed that resistance develops in part because CRPC cells adaptively up-regulate androgen receptor levels through overexpression, amplification, and expression of ligand-independent variants in response to chronic exposure to a low-testosterone environment.
“We call it bipolar because we get the extremes with very high and very low levels of testosterone therapy,” said study investigator Samuel Denmeade, MD, who is a professor of oncology at Johns Hopkins University School of Medicine in Baltimore, MD.
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He and his colleagues conducted a pilot study in which 16 patients with asymptomatic CRPC who had low to moderate metastatic burden were treated with three 28-day cycles of combination testosterone cypionate and etoposide.
The men received a 400 mg intramuscular injection of testosterone cypionate on day 1 and oral etoposide (100 mg daily) on days 1 to 14.
Castrating therapy was continued in order to suppress endogenous testosterone production and to allow for the rapid cycling from supraphysiologic to near-castrate serum testosterone levels.
The researchers found asymptomatic men with advanced CRPC could be safely treated with BAT and achieve rapid cycling between supraphysiologic and near-castrate serum testosterone levels.
Using this approach, the researchers found there were PSA flares in some of the patients but there were no symptomatic flare reactions with BAT administration. In addition, BAT produced objective radiographic responses in 50% of patients.
“It is safe and we see the men feel very good, but further testing is need,” Dr. Denmeade said in an interview with Cancer Therapy Advisor. “The secret of our success is getting the level up so high. We hope to eventually come up with a specific product and we hope to explore the best way to deliver it and what may be the best delivery system such as a cream instead of the injections.”