Dr says Enzalutimide... what about Cabazitaxel?

[Tak-Druk]

Hi Folks... looking for shared wisdom/thoughts/opinions/experiences to help me in my current decision point.

I've made it into my 50s, living with cancer for about 8 years now...

2012: Diagnosis Gleason 4+4=8 and tx with Cyberknife (PSA 21)

2014: Scans confirm metastatic disease confirmed in lungs and one bone lesion (PSA 10), tx with 6 rounds Docetaxel and begin Lupron/Casodex

2018: PSA first becomes detectable after 3+ years on Lupron/Casodex, discontinue Casodex but no appreciable drop in PSA. Approved and received Provenge.

2019: April: Biopsy to investigate blood clots in urine shows cancer cells in urethra bladder opening (PSA .07). December: Scan finally show new tumor growth - bone lesion, pelvic lymph node, new nodules in lungs (PSA 1.23)

Present day- time to bring on a new obstacle to the cancer growth. Doctor recommends Xtandi (enzalutimide). I'm wondering about going back to chemo first with Cabazitaxel. My thinking was inspired by this recent study (ncbi.nlm.nih.gov/pubmed/315... "CONCLUSIONS:

Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen-signaling-targeted agent (abiraterone or enzalutamide)."

What would you do and why?

Would Cabazitaxel make me ineligible for PARP inhibitor studies? (My doc says I have to fail on Xtandi first... I have a CHEK2 mutation).

I am also in contact with a different doc who is doing interesting things with various cancers including PCa, using low-dose metronomic chemo and alternating treatments. I'm bringing these questions to both docs. Any experience with this decision process would be welcome. In the end, I believe there is no "right" answer, I'll just do the best I can with the tools and information I've been given and live with the results (and eventually die with the results as well.)

It feels a bit more sad and scary at this point, because most treatments seems to be talking in terms of months instead of years.

Thanks for your consideration and any responses...

[cesces]

Why not both.

I believe there's a recent clinical trial supportive of such an approach.

[Tak-Druk in reply to cesces]

Thanks... I'm waiting to hear my docs opinions on this too. My sense is that my primary MO likes to get the most out of each intervention by stringing then along sequentially.

[Tall_Allen in reply to Tak-Druk]

The combination of docetaxel + Xtandi for mCRPC increased progression-free survival and reduced PSA vs docetaxel-alone at 6 months, but the benefit was short-lived. There was no benefit in overall survival, and toxicity was higher for the combination.

urotoday.com/conference-hig...

[abmicro in reply to Tak-Druk]

ditto

[Tall_Allen]

Cabazitaxel is approved for men in whom docetaxel no longer works, although your MO can probably get it for you anyway. I like alternating hormonal and chemo therapies, and think it's a good idea to try an advanced hormonal therapy (Xtandi or Zytiga) before trying another taxane.

After that, you can try cabazitaxel + carboplatin. Often platins are effective in the same cases where PARP inhibitors are effective. So if the chemo cocktail works for you, you can try a PARP inhibitor afterwards as a maintenance therapy. It is too early to tell from TRITON 2 if it works against CHEK2, but by then there will be more data.

After that, you can try Xtandi or Zytiga (whichever you haven't tried). Sometimes the chemo will resensitize the cancer to the advanced hormonal.

[Tak-Druk in reply to Tall_Allen]

Thanks Tall Allen. I appreciate your opinion and contributions here.

[cesces in reply to Tall_Allen]

Ta, what do you think about concurrent

hormonal and chemo therapies?

Is there any data out there on this?

[Tak-Druk in reply to cesces]

Hi Cesces... not sure about concurrent therapies. The question would be for me: if I can get X months/years controlling growth with Enzalutimide and Y months/years controlling growth with Cabazitaxel, can I get X + Y + Z months/ years by combining the two concurrently? It would need to have the "Z" factor of added time to be worth combining. I don't know if they would amplify the benefits together in that way.

My MO seems to think that pulling the trigger on two treatments at once is a waste of ammunition, and I'd be better off stringing out each individual intervention for as long as it helps. So my question is really which order would be best... wondering if hitting the tumors with chemo first, might make the Xtandi more effective.

However, I also appreciate Tall Allen's suggestion above that Xtandi, then chemo, the Zytiga could be a good sequence.

[cesanon in reply to Tak-Druk]

1. I will always defer to TA

2. I do recollect some statistics based research that has been confirmed by clinical trials, that evidenced that when you have growing populations of adaptable prostate cancer cells.... that it is best to hit them hard with everything at the beginning as opposed to sequencing treatments. But Ta basically has all the research in his head in a giant spread sheet... so I would listen to his recommendations. I myself would probably take them over that of my own Docs. And what he is talking about is specifically targeting the PCA's behavior.

[Tak-Druk in reply to cesces]

I do think I had a really good run on Lupron by combining with Docetaxel at the outset. The idea I have from this is that the chemo knocked back the cancer so the Lupron had less work to do and might have been more effective. Thus my thinking that Cabazitaxel before Xtandi might be similar (which I guess could be concurrent also, as in my initial experience with Docetaxel/Lupron.)

[cesanon in reply to Tak-Druk]

"chemo knocked back the cancer so the Lupron had less work to do and might have been more effective"

Agreed. That was my thinking. But Ta's thinking is a lot more nuanced. Make sure he has the full detail of your medical history, then ask him to confirm his recommendation.

[Hidden]

I would agree with your doctor about going to a second-line ADT drug and not to chemo at this point. I chose Zytiga, but Enzalutamide is also a good choice.

Something else you can start looking into is molecular testing for mutations that have targeted treatments avilable for them.

I would save chemotherapy for after the second-line ADT stops being effective, then possibly go back to another androgen-based drug after chemotherapy.

I have discussed possible chemotherapy after Zytiga with my doctor. He looked at how long it took for my PSA to rise after chemo to determine whether Docetaxel had been effective and worth rechallenging. Since my PSA rose again within 6 months, he felt Docetaxel would not be effective enough to rechallenge and I should go straight to Cabazitaxel.

[Tak-Druk in reply to Hidden]

I appreciate your input... helpful. Thanks. Your choice seems to align with TAs info below! I believe that I've done a Guardant test, but I think that a fairly recent one did not come up with any free floating tumor cells.

[Tall_Allen]

I think you should also consider Zytiga before Xtandi:

pcnrv.blogspot.com/2019/12/...

[Tak-Druk in reply to Tall_Allen]

Wow TA... thanks so much. That link is awesome, with great info that's easy to digest. My doc seemed to suggest that I would weather the Xtandi side effects well since I'm relatively young and fit, and that was a selling point to do it first... but now I'm curious to get more info on why she didn't go with Zytiga. I'm going to use that article to jump start this conversation.

[immunity1]

You have given us a decent summary of your recent history. Given the information we have at hand I like the idea of using alternating treatments or even better, combining them. Cost may come into it also. I would recommend other than what your MO has suggested or has been mentioned on this site. Namely, Lu177 treatment following a PETScan to detect whether your lesions are PSMA-avid or not (in which case this treatment is invalid). But you will be up for $60K or so, for a course of 4 treatments (the number may vary). I had this treatment 3y ago and it delayed progression of soft tissue pelvic lesions for ?2y. As a second choice I would use Zytiga before Xtandi; both before Cabazitaxel. Yes, the sadness as the road gets a little bit steeper. All the best. =Rob

[j-o-h-n]

"talking in terms of months instead of years." How about 360 months ? My bet....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 02/20/2020 6:49 PM EST

[Tak-Druk in reply to j-o-h-n]

Right on... I'll take it! Thanks

[Patrick-Turner]

My doc said Cabazitaxel tended to work a bit better than Docetaxel where this had failed. But the studies I have read say Cabazitaxel is only marginally better than Docet.

While on continuous ADT, Taking Cosadex, Xtandi, Zytiga after ADT alone fails to hold down Psa will only delay the Pca progression and mean time for the delay gained is months not years. PsMa scans showed my countless soft tissue mets and bone mets grew bigger and more numerous while on Zytiga, Psa went from 6 to 2 for a couple of months then rose to 12, so I had 5 shots Docetaxel and Psa went from 12 to 50, and doc declared Docet failed at 4th shot, and referred me for Lu177, available here in Sydney, near where I live in Canberra 300km away. In Nov 2018, I began Lu177,had 4 shots by May 2019, Psa went to 1.6, but I'd also begun Xtandi after 3rd Lu177, so Psa continued down to 0.32 last Nov 2019. But now Psa is doubling in a month and is about 1.5, and CT scans showed to active bone mets but nothing else. I might need more Lu177. I have been fighting Pca since 2009, diagnosed Gleason 9 at age 62.

If you have good scan results with PsMa Ga68 PET/CT scans then perhaps Lu177 works especially well on soft tissue mets for you, but you need to get that scan. Your Pca may not all be treatable by Lu177, or chemo, because Pca can become a variety of different types of Pca so other scans, and tumor DNA analysis may be needed to match treatment to what is found in analysis. Many doctors may not be aware of who to refer you to for the more complex treatments. do not know

ADT, Cosadex, Xtandi, Zytiga are all anti male hormone drugs that stop its production in your testicles and adrenal gland, and interfere / block testosterone in tumours, but these don't seem to kill Pca cells. Pca is often slow growing so chemo only kills dividing cells for a short time while active in the body. EBRT had hardly any effect on my Pca. But Lu177 seemed to be the one to kill the most Pca cells, and with negligible side effects. Chemo has the worst lasting side effects, and not a very good record for extending OS time.

If I were you, I'd get a PsMa Ga68 scan tomorrow if possible. Without knowing full Pca status, your Pca treatment become guesswork. Lu177 is available in Germany.

Patrick Turner

[Tak-Druk in reply to Patrick-Turner]

I'm very interested in PSMA scan and Lu-177... I don't think anybody has the scans in the Seattle area... I was told I would have to go down to Portland. Also, cost would be an issue.

[Patrick-Turner in reply to Tak-Druk]

I live in Australia where PsMa Ga scans and LU177 therapy became available.

The PsMa Ga68 scans are PET and CT done using radioactive Gallium, and this type of scan indicates whether you would get a benefit using Lu177, that is radioactive Lutetium, administered in same way at the Gallium is, and you sit in a chair for awhile. I had to travel 800km from Canberra to Melbourne for my first PsMa scan in 2016, so I flew on plane and talked to a doctor after and stayed a night, and scan cost about usd$350. The whole trip was expensive. So what. It had to be done IMHO, and I had the dough.

Lu177 is given during what is called Theranostic Treatment, and I suggest you google that. Thereanostics Australia explain it, and companies in Germany where you may have to go to get Lu177 also explain it.

PsMa scans became available locally, so I didn't have to travel again to get scans, but then Lu177 became available in Sydney, so I had to travel only 300km to get that, so a slow train ride was fine- funded by Govt for pensioners.

I spent usd $27,000 on Lu177 plus 3 scans, and traveled 4 times to Sydney over 6 months. Medicare paid nothing, and I ain't insured, so its right out of my pocket, but I think well worth it. I would have been forced into palliative care if I had not used Lu177. Patrick Turner.

There are rules about Lu177 treatment, and you need a doctor's referral to get it

Patrick Turner.

[VictoryPC]

Intermittent Xtandi along with PCSPES. It works for me and a host of others. Xtandi is great as long as you maintain response to it. On 3 months, off 4 usually.