Enzalutamide and PSMA

[Blair77]

Below is an article posted in urotoday. Too bad my husband doesn’t have any left he can take before his PSMA scan on 1/23. Article:

There is preliminary evidence for prostate-specific membrane antigen (PSMA) upregulation effects of androgen receptor blockade in prostate cancer. In an attempt to find the best condition for PSMA radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC) patients, we evaluated the effect of oral enzalutamide in patients, predominantly having previously progressed on enzalutamide treatment.

Ten patients with advanced mCRPC scheduled for PSMA radioligand therapy were examined with 68Ga-PSMA-11 PET/CT before and after a mean of 11.8 days of enzalutamide 160 mg/day. Imaging results were compared using total PSMA tumor burden quantification. We assessed whole-body total lesion PSMA (TLP), defined as SUVmean × tumor volume and calculated TLP-to-liver ratio (TLP-LR), TLP-to-parotid gland ratio (TLP-PR), and TLP-to-kidney ratio (TLP-KR).

The mean (median) increase of TLP-LR, TLP-PR, and TLP-KR in the cohort was 49.3% (38.8%), 45.1% (23.5%), and 54.9% (37.6%), respectively. These increases were statistically significant (p = 0.002, p = 0.014, and p = 0.014), while PSA values did not change significantly (p = 0.846). Seven of the 10 patients had previously undergone enzalutamide treatment with eventual progression, formally classified as treatment failure. No side effects were noted in the short term.

Our results suggest that enzalutamide could be considered as a PSMA radioligand treatment enhancing primer medication, which may increase PSMA expression by a dimension of 50% in mCRPC. The effect was shown even in patients having previously failed enzalutamide treatment for arrest of progression in the mCRPC setting. Our observation deserves evaluation in a prospective setting.

European journal of nuclear medicine and molecular imaging. 2020 Jan 03 [Epub ahead of print]

Florian Rosar, Sebastian Dewes, Martin Ries, Andrea Schaefer, Fadi Khreish, Stephan Maus, Hendrik Bohnenberger, Johannes Linxweiler, Mark Bartholomä, Carsten Ohlmann, Samer Ezziddin

Department of Nuclear Medicine, Saarland University, Kirrberger Str. 100, Geb. 50, 66421, Homburg, Germany., Department of Urology, Saarland University, Homburg, Germany., Department of Nuclear Medicine, Saarland University, Kirrberger Str. 100, Geb. 50, 66421, Homburg, Germany. [e-mail].

[tango65]

Please, see this link posted yesterday:

healthunlocked.com/advanced...

[Tall_Allen]

It's temporary.

[Blair77 in reply to Tall_Allen]

Right, but wouldn’t it help if your about to do lu 177? Wouldn’t you want the max uptake?

[Tall_Allen in reply to Blair77]

Yeah - why not try it?

[Blair77 in reply to Tall_Allen]

I doubt Dr Aggarwal will prescribe it for him ☹️.

[Tall_Allen in reply to Blair77]

He might. Show him the study and see what he says. If it conflicts with the rules of his clinical trial, he can't. Getting insurance to cover it may be problematic anyway. BTW, I met Rahul Aggarwal and really like him - I found him to be very flexible and knowledgeable..

[Blair77 in reply to Tall_Allen]

I think I will ask, just so I can’t say I didn’t try. My husbands getting the LU177 outside of a clinical trial so it won’t mess with any regulations. Dr Aggarwal is personable and I think he knows his stuff. However, he really likes treatments that have strong clinical data. He wasn’t really excited when I told him we were going to try LU177 in Germany, he wanted my husband to stick with chemo or other proven therapies.

[MichaelDD in reply to Blair77]

I too am with Dr Aggarwal. I would ask him anything. When my GS68-PSMA scan found my lung metastasis he formed a plan with my other oncologist.. He said to me "we are going to have you around for years-not months". That was a year and 3 months ago. I could not have been blessed with a better medical team then what I have now.

[Schwah in reply to Tall_Allen]

Might it also help right before a psma scan to better light up any PC lesions?

Schwah

[DakotaDon]

Hi Blair 77,

I have been squirrelling away some Xtandi for lean times and just learned I have received another grant from PANF for more funds this year. Therefore, I could happily send you a two weeks supply if it would help. Please private message me at [e-mail] if interested.

DD

[MateoBeach]

There are other studies of enzalutamide for enhancing PSMA expression for 177 LU-PSMA treatment underway in Australia. The caveat is being castrate resistant (and probably already being on ADT therefore). For HSPCa starting enzalutamide is expected to reduce PSMA expression, as does when starting ADT de novo. This is currently being sorted out.

I am currently mHSPCa and am undergoing ADT "washout" to recover non-castrate T levels before my first Lu-PSMA treatment to (hopefully) improve PSMA expression. I will likely do the enzalutamide before a second treatment to cover both bases, since this is not yet known for hormone sensitive persons.