Xtandi and T Level

Hi all
Husband has been on Xtandi now since April 2015, doing well with no real side effects and great reduction of PSA. Became castrate resistance on Lupron after only 4 months PSA started rising to 2.1 after falling only to a low of 1.3. In April before started Xtandi T level was 25. In May PSA went to 0.7 and T went to 48, this month PSA down to 0.3 (which is great) but T is now 50. What the heck???? Is still receiving Lupron every 4 months. Has anyone seen this or is there any studies on this? Haven't really been able to find much of anything. Not seeing urologist until August. Give me your thoughts!!!
Thanks
Dawn

In my simplistic way I think of Zytiga as super Lupron and of Xtandi as super Casodex.

As a G9, you may want him to switch from a urologist to a medical oncologist who specialzes in PCa

Hi Dawn,

It sounds like the Xtandi is doing just what it's supposed to do. It doesn't stop T from getting manufactured, it just blocks its use by the cancer cell.

It also sounds like extraprostatic sources of T (mostly from the adrenals) are kicking in.

That's why I like the idea of taking Lupron (or Firmagon) together with both Zytiga and Xtandi. When you take one after the other it doesn't work very long because you get cross resistance. Zytiga shuts down adrenal and intraprostatic sources of androgen, Xtandi blocks androgens from getting used and prevents the androgen receptor from going inside the cell where it is invulnerable. This combo is available in clinical trials, but sometimes a good medical oncologist can talk the insurance company into it.

Of course, the best thing he can do to extend survival and quality of life is to go for a course of Taxotere (usually 6 cycles at a time with infusions every 3 weeks). Lots of studies now showing that it works better with earlier use.

- Allen

Fnp256 said...
Had a consult with med onc about 3 weeks ago concerning starting Taxotere. Was told that because husband is already castrate resistant he does not meet protocol for early Taxotere cycles.

I agree that he does not meet the CHAARTED protocol, which is for hormone sensitive cases with multiple mets. However, Taxotere was approved for use in metastatic castrate resistant PC in 2004, and can certainly be started now, if your medical oncologist agrees. The fact that the survival advantage starts at 17 months while hormone sensitive and goes down to 2.5 months when castrate resistance, seems to argue for using it sooner rather than later, whatever the hormone responsiveness level.

Fnp256 said...
As he is already on Xtandi and there are no studies of patients on Xtandi receiving Taxotere there is no protocol for treatment at this point so he must start to fail Xtandi before Taxotere can be started.

He is correct that chemo is effective after Xtandi and Xtandi has been FDA-approved for that use. It is also true that Xtandi is more effective used earlier (as most drugs seem to be) compared to how it used to be used - only after chemo.

Waiting for one medication to fail before starting another has been the standard of care. It reflects a sequential approach. The alternate POV is what I call the "cocktail approach." While there are no published studies yet on the cocktail approach, it is in numerous clinical trials. On the other hand, we know the failings of the sequential approach. Xtandi and Zytiga create cross resistance to one another when used sequentially, with or without docetaxel in between. Waiting for failure means waiting until the cancer has devised strategies for getting around the other medications as well. Will the "cocktail" approach work any better? I certainly can't guarantee that. It's just a shot.

All we have so far is the early results of a small pilot study that showed that the combination of Zytiga and docetaxel was effective at reducing PSA by more than 50% in 90% of patients, and by more than 90% in 70% of patients. These are higher levels than we would expect from either alone.

Phase 1b study of abiraterone acetate (AA) and docetaxel (D) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Fnp256 said...
We will certainly be talking to the, though about adding Zytiga along with the Xtandi. Do you have any documentation to studies showing the advantage to the combination?

So far all we have are the interim results of one of the clinical trials of the combo in patients with mCRPC. PSA was reduced by more than 50% in 76% of the patients, and by more than 90% in 45% of the patients.

Enzalutamide (ENZA) in combination with abiraterone acetate (AA) in bone metastatic castration resistant prostate cancer (mCRPC).

I think you can start to see why I suspect a cocktail of all 3 agents might work better than a sequential approach.

- Allen