Hormone refractory/ castrate resistant

[Blair77]

If you respond to Zytiga/ Enzalutamide are you still considered hormone sensitive? I assumed my husband was hormone refractory once his PSA started rising on Lupron/ Casodex combo. It’s still to be determined if he will respond to the Enzalutamide.

[Cmdrdata]

Good question. With the advent of new (last few years) hormonal drugs and others in the pipeline, I wonder if the definition have now changed?

[pjoshea13]

They used to think that when a man failed ADT he had become "hormone refractory". When it was realized that the androgen receptor [AR] continued to play a role in most cases, the term was replaced with "castrate resistant".

& so we now have Zytiga to close off adrenal sources.

Androgen can be synthesized within the cancer cells. e.g. DHT can be derived down a path that does not include testosterone. Avodart can block that. And a statin can deprive the cells of cholesterol, which is the starting point for steroid hormones.

To block androgens that manage to get through, there are the AR antagonists - Casodex, Enzalutamide, etc.

When they have figured out to eliminate the AR axis entirely, will we have durable remissions - or will they need to revive "hormone refractory"?

-Patrick

[Blair77 in reply to pjoshea13]

Thank you!

[Hidden]

If you respond to Zytiga or Xtandi you are still hormone sensitive. The cancer just becomes better at using smaller amounts of androgens to reproduce. This is why they refer to it as "castrate resistance". The "castrate" level of androgens eventually becomes high enough for the cancer so further reduction or blocking is required. Testosterone levels of around 15 are common with castration, but Zytiga for example will further reduce them to close to zero. Xtandi blocks the receptors. Either way, both of these drugs will only work if the cancer is hormone sensitive.

[Tall_Allen]

"Hormone sensitive" means the cancer is still sensitive to castration.

"Castration resistant" means that PSA increases in spite of castration levels of testosterone.

Second line hormonal agents (e.g., Zytiga, Xtandi, Erleada) are effective in spite of castration resistance.