BIPOLAR ANDROGEN THERAPY (BAT):  A Heads Up:   A BAT Protocol is Now Open for Enrollment at the Seattle Cancer Care Alliance 

The Bipolar Androgen Therapy (BAT) — What is it? The Pilot Study: 

The pilot study evaluating BAT therapy was reported in Science Translational Medicine, Jan 7, 2015, authored by Drs. Schweizer, Denmeade et al.: “Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer (CRPC): Results from a pilot clinical study.”  The term “bipolar” reflects the design of a new therapy regimen which rapidly alternates from a supraphysiologic level of serum testosterone (T) to a near-castrate level in the course of one month in repeated cycles.

The concept underlying the BAT is that rapid cycling from very high to low levels of T would maintain cancer cells’ sensitivity to androgen deprivation and may delay the progression toward CRPC, a routine development in the course of androgen deprivation therapy (ADT) due to cellular adaptation to a persistently androgen-depleted state. Another mechanism under consideration is that supraphysiologic doses of T are toxic to prostate cancer cells by interfering with DNA replication or inflicting double-stranded breaks in DNA, a lethal injury.

The pilot study evaluated 16 asymptomatic men with CRPC with low to moderate metastatic burden. The patients remained on ADT with an LHRH agonist, e.g. Lupron. The regimen began with a 400 mg intramuscular injection of testosterone cyprionate which, in 2 days, raised serum T level to >1500 ng/dL. This was repeated monthly.  At day 14 the serum T averaged ~600 ng/dL and by day 28 the T level averaged ~150 ng/dL.  The normal T level is between 130 – 700 ng/dL. “After three cycles, those with a declining prostate-specific antigen (PSA) continued on intermittent testosterone therapy monotherapy.” At the onset of BAT all the patients were progressing during androgen deprivation therapy (ADT) and failing additional androgen suppressive regimens.

The median values for age of patients was 71; PSA, 20 ng/mL (range 1.4 – 819);  T level < 20 ng/dL; and length of prior continuous ADT, 45 months. 75% had Gleason score > 7. Thirty percent of the men had 2 or 3 prior therapies.

The BAT treatment was well tolerated. The most common side effects were edema, hair loss, fatigue, and nausea — all of mild to moderated severity.  (A chemotherapy agent, etoposide, was used for three cycles in the pilot study, but is not included in the current protocol.)

 

Results of the Pilot Study:  Seven of 14 evaluable patients had “high-rates” of PSA response; 5 of 10 showed radiographic improvement.  “Although all patients (10 of 10) showed eventual progression, four men remained on the BAT for more than one year.”

 

The conclusion:   The key finding was that in this group of men who were progressing on ADT therapies before BAT, “All patients (10 of 10) demonstrated PSA reductions upon receiving androgen-ablative therapies after BAT, suggesting that BAT may also restore sensitivity to ADTs.”

 

The Current BAT Protocol Now Open for Patient Registration

(See NCT02286921 at Clinicaltrials.gov for details).

The protocol requires that “Eligible patients will have metastatic disease CRPC with no disease related symptoms and progression on ADT and will have progressed post-treatment with abiraterone.” ADT

will be continued. One additional prior treatment with second-line hormone therapy is allowed. The primary endpoint is radiographic progression.

The patients are randomized (see schema below) between BAT and Xtandi (enzalutamide). There is a “cross-over” feature after the failure of either BAT or enzalutamide.

 

The Protocol Schema:   This protocol fits nicely into clinical practice since abiraterone (Zytiga) is the most common secondary therapy after progression on (say) Lupron. The protocol is available at 15 locations in the USA and the target for enrollment is 180 men. (“SOC” in the schema refers to standard of care.)

For registration In Seattle the principle investigator is Dr. Michael Schweizer. Contact: (206) 288-6252; email, [email protected].

 

BOTTOM LINE: If found effective, the BAT regimen could offer a promising new therapy for prostate cancer.

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