ASCO 23 - Transdermal square-wave testosterone therapy

[pjoshea13]

This might interest followers of BAT.

As you no doubt know, Denmeade's BAT cycle is a 28-day modulation of testosterone [T] from ~2,000 ng/dL down to near castrate.

The BAT cycle typically begins with a T-cypionate injection into muscle.  In the new pilot study, T was delivered daily, transdermally, for a minimum of 12 weeks.  The dose was adjusted, as needed, to reach the target of 900-1,500 ng/dL.  Upon disease progression, therapy was switched to Enzalutamide (Enza) until progression.  (This could be repeated again within the 12 month study period.)  As with BAT, the men had CRPC & on ADT throughout.

For results, see: meetings.asco.org/abstracts...

[cesces]

I always wondered about the 4 week cycle.

What is the right cycle and why.

Using the patches isn't so obvious to me.

[MateoBeach]

Square wave is a better framework for designing BAT regimens. The original, one injection of 400mg T-cyp every 28 days is more a sinusoidal variation. Not maintaining y truly high T levels above 1500 ng/dL for long, then Just a gradual decline because of the 7 day terminal half-life. Never getting to castrate level by the end at 28 days. So it does not actually provide good alternating exposure to Hera high T levels and then castrate T levels.

I and others are working to optimize more sensible regimens but it also depends upon the aggressiveness (growth rate ) of the PC which is suggested by the PSADT. For slower growing cases, longer cycles seem more appropriate. For me that is now 12 weeks of high T via 400mg T-cyp every two weeks. But for the last 3-4 weeks I switch to testosterone gel so it will be quickly cleared at the end of the high T cycle. Then go to castrate sharply (square wave) with Orgovyx ADT for a month, and include darolutamide AR blockade for the first week. Still a work in progress. But makes more sense than the original BAT protocol to me.

Smurtaws experiments with very rapid micro cycles or pulses are entirely different and might have greater efficacy. But for me, I want to stick with one general strategy for longer to evaluate durability of my currently favorable response. Paul / MB

[Ramp7 in reply to MateoBeach]

Good points to consider: Aggressive nature of individuals cancer. I like the steep cut off in T, as opposed to a gradual reduction. Cycle length. Even an adaptive theory component to BAT.

[Ramp7]

The approach I have employed and discussed with Denmeade is to have Lupron has a background agent while administering T. But the idea of Xtandi is a good consideration. To date I have only completed one cycle. Initiation of the second one should commence soon.