Docetaxel Extends Enzalutamide Effectiveness

[Tall_Allen]

This is our first proof that resistance to enzalutamide can be reduced with docetaxel. It also shows that triplet therapy may be beneficial in patients who have already progressed to castration resistance. We would expect a larger effect if used at the first sign of castration resistance.

prostatecancer.news/2022/10...

[Seasid]

good news about docytaxel.

[cesces]

Thanks. Nice article.

[FISHLAND]

merci pour toutes ces informations précieuses

[Vishwa1890]

What is the effectiveness other way around? My dad had few cycles of docetaxel and then switched to Enzalutamide, after PSA rise.

[Tall_Allen in reply to Vishwa1890]

This may assist in your sequencing decision.

prostatecancer.news/2019/12...

[alephnull]

Thank you Tall_Allen!!

Because I have developed some concentration and other cognitive issues, is this saying:

My take: Starting docetaxel and continuing with enzalutamide WHEN enzalutamide starts to fail, will restart enzalutamides effectiveness.

OR

Should docetaxel be started before enzalutamide starts to fail.

[Tall_Allen in reply to alephnull]

The former

[EdBacon]

I got nothing on Xtandi after Zytiga. After 3 cycles of Cabazitaxel, I decided to start using the Xtandi I have left over in addition to the chemotherapy.

Don't know what the effect on my PSA is yet since I just started, but I had a complete reduction in hip pain that was making it difficult to walk. I would not be surprised if Xtandi is working again after a few cycles of chemo since it's been proven in the CARD trial.

I do get pain relief from Cabazitaxel for the first week or 2 after infusion, but then it comes back before the next infusion. Adding Xtandi takes it back down again so I'd guess it's working. Still waiting to see what effect it's having if any on PSA. In the meantime, I'll take the pain relief.

I think the combination of chemo and Xtandi should be explored more.

[Seasid in reply to EdBacon]

if something is reducing your pain it must be working.

[EdBacon in reply to Seasid]

Right. Can't see another explanation. As much as I hate pain, it can be very useful. It's the one of the ways your body talks to you. My pain has tracked very well wth progression. You just can't look at the "micro" level of every little ache or pain.

It's interesting that the Cabazitaxel chemo also reduced my pain from full time Norco level to pain free in around 4 days after infusion. For the first cycle, it lasted through to the next infusion. After that, the pain returned, but only after 2 weeks out from infusion. Added Xtandi and it was gone again within 3 or 4 days. It seems like the chemo works, but the cancer recovers from it before the next infusion.

There was a small phase 2 trial where they put patients on Xtandi with Cabazitaxel. There were 10 guys that had previously been treated with Zytiga like me. 3 of them had a PSA response of over 30%. I know it's a small sample, but well worth a shot especially if it's safe and you have the drug on hand. So glad I tried it. I am still pain free today. I'll take every day I can get.

[Seasid in reply to EdBacon]

what dose of Enzalutamide parallel to Jevtana reducing your pain? Full or half? Are you starting Enzalutamide only when you start feeling the pain?

[EdBacon in reply to Seasid]

I'm doing the full dose of 4 pills (can't remember how many mg. that is). I started using it at the end of the cycle when the pain started just to see what would happen. Then after it worked, I started using it following the protocol in the phase 2 trial. The patients in that trial took Xtandi every day except the day of infusion. The main difference is that in the trial, they were taking Cabazitaxel at the 25mg square meter vs. my dose of 20mg. per square meter.

ascopubs.org/doi/abs/10.120...

[Seasid in reply to EdBacon]

thank you very much

do you have a link to that phase Ii clinical trial?

[EdBacon in reply to Seasid]

clinicaltrials.gov/ct2/show...

[Seasid in reply to EdBacon]

thanks for the link

[Seasid in reply to EdBacon]

i believe that 20mg/ m2 should be fine

[EdBacon in reply to Seasid]

That's right. The 20mg dose was proven to be non-inferior in the PROSELICA trial. This trial is what the current recommended dose is based on.

ascopubs.org/doi/full/10.12...

[No17]

thank for the info. I'll eventually be at that cross road. Curious to see if a similar conclusion voulons be made for Darolutamide/Nubeqa

[Seasid in reply to No17]

nubeqa also stops working and it is similar to the other drugs Apalutamide, Enzalutamide

[Tall_Allen in reply to No17]

Probably so. Triplet for newly diagnosed also works with Nubeqa.

[MateoBeach]

I applaud the careful work that went into this study and I salute the heroic participants.

Unfortunately, it is testing a situation that we now know is not optimal: 2nd generation AR drugs should be used along with ADT when started and still HSPC rather, than waiting for castrate resistance to develop before adding them, as with these men. Then only about 1 in 3 had a response at 13 weeks and subsequently progressed. That was the P2 group and already in a tough situation. So docetaxel certainly worth the try at that point. But only gained median longer PFS of approximately 2 months ( 10 Mo vs 8 Mo roughly.)

[Seasid in reply to MateoBeach]

i agree with you but unfortunately nobody wants to pay for a triple therapy outside of the US

In Australia, Canada and UK healthcare system they don't want to pay

[EdBacon in reply to Seasid]

Same reason that Australia, Canada and UK don't prescribe Provenge. At $23K per month of life extension, they feel that the money can be used more effectively somewhere else.

[Seasid in reply to EdBacon]

i would pay for Provange but it is not even approved in Australia and you can't get Provenge here even if you would pay out of your own pocket.

you can get Xofigo in Australia but you should save up 60k A$ for 6 infusions.

in UK healthcare system they would pay for Xofigo but they are not putting giving you Prolia or Zometa infusions therefore you are simply not eligible for Xofigo on that ground as it could break bones without bone medication.

[Tall_Allen in reply to Seasid]

They will eventually, I think.

[Tall_Allen in reply to MateoBeach]

Most of the men in the study were recurrent, so Xtandi (or chemo) was not standard of care until they became mCRPC.

[Rocketman1960]

Great News! Thanks TA!