Update on failing Enzalutamide

[CrocodileShoes]

Hello again friends,

I wrote recently after learning that Xtandi was no longer working, seeking options. Since then I have had a consultation with my Oncologist and we went through the (limited) range of options for someone who is living in the UK and being treated on the National Health Service.

Brief recent history: a couple of years ago PSA started to rise on the treatment that had worked well (bicalutamide and 3 monthly Prostap injections) So I switched to Xtandi just over a year ago. The side effects were horrendous, so I reduced dosage to one-quarter of usual dose. PSA initially fell, and once I'd recovered from an unconnected major surgery, moved back to the full dose. This floored me with exhaustion and, as the PSA doubled (to 3.3) I went back to one-quarter dose. After 3 months, PSA had risen (4.4) but more slowly. But it was clear that it was not the drug for me. So at last month's consultation, I began by asking if I could switch to one of the other 'mides' (Apalutamide, Darolutamide, etc) Our National Health Service is a national treasure, but the official guidance is that, once you've failed Enzalutamide, that's it - no more options.

I know that some of you have had some success switching, but I was told that I'd have to pay privately.

His option was chemo. I said no thanks - not yet.

Long story short: I asked for a second opinion, one that was up-to-date with all the latest trials. To his credit, that's now done and on July 27th, I will meet with Johan De Bono (or one of his earthly representatives, at the Royal Marsden Clinic. Johan's reputation precedes him and I know that he's leading the Lu-177 clinical trial and a few others besides.

I want to keep all options on the table. I have a pretty slow spread of mets (all bone) and my PSA is still modest. So, I don't want to be panicked into hasty action.

My inclination at the moment is to go stay with my friends in Melbourne and ask the Peter Mac centre to treat me as an international patient. Since the UK charges FOUR TIMES the costs in Melbourne or Perth, it's cheaper to go down under. Plus, they did a PSMA scan on me a couple of years ago, and I seem like a good candidate.

I'm not against chemo, and I know it will be a requirement one day, but it seems that sequencing is important, and my desire now is to hit it hard. That said, I've seen quite a few posts recently where Pluvicto has been short-lived in its effectiveness and it's a lot of money. So, here are my questions:

1. Do people concur with my onco, that once Enzalutamide has failed, it's really not worth pursuing the other 'mides'?

2. Can anyone recommend men on here who have travelled to Australia for Lu-177 treatment, so that I can pick their brains?

3. Is my resistance to chemo, logical or rational, and if I did follow UK SOC, would it have a negative impact down the line?

4. Finally (and I'm sorry there are a lot of questions), what else should I be putting in front of Johan De Bono as possible next steps (perhaps as combo packages)? I'm thinking of Cyberknife, BAT, Cisplatin, PARP inhibitors and Immunotherapies. But I'm trying to keep a completely open mind on this.

I wrote a book a few years ago about the rise in self treatment. I met a leading oncology researcher whose brother-in-law had just being diagnosed with glioblastoma. When I asked him about 'alternative' treatments, he said, 'It's funny, I used to tell people that was all quackery. And then when someone you love has glioblastoma, you find yourself Googling peach kernel extracts, clinics in Mexico and God knows what else. Conventional medicine has a lot to learn from impatient patients.'

Stay well, my friends - the lines are open......

[Tall_Allen]

The PRESIDE trial showed that docetaxel can extend enzalutamide effectiveness.

prostatecancer.news/2022/10...

Your post saddens me. I hear it all the time from patients who are fearful and ignorant about what docetaxel is really like. I blame movies, and patients who think that all chemo is alike. I'm not saying it is without side effects, but I do know that QOL is markedly better afterwards. I also know that waiting to use it later assures worse side effects and worse oncological results. I hope you will reconsider.

[CrocodileShoes in reply to Tall_Allen]

I appreciate your concern, TA. As I said, I've got no objection to forms of chemo - I know they've changed . My issue would be that Enzalutamide severely affect my QOL, so it's not an end-point that I'd want to aim for. And as Benkaymel confirms, the NHS would not allow me to switch options to apalutamide, et al. So, it would have to be chemo in tandem with something else for me. And I want to get a best guess on which would be most effective: chemo or Lu-177. I have no health care insurance (most people never need it in the UK) so I'm not crazy about spending significant amounts of money going to Australia. But the SE with Lu-177 do seem to be mild.

[HopingForTheBest1]

I was on combo chemo treatment of Cabazetaxel and Carboplatin. Had no serious side effects, and kept my hair. Unfortunately, after 13 treatments no real benefit. Went on to Pluvicto, as prior chemo treatment is required. Jury is still out after 4 treatments as to effectiveness. $135k billed to insurance for each Pluvicto treatment, and they paid $43k. My cost $0.Seeing DeBono is a great choice.

[CrocodileShoes in reply to HopingForTheBest1]

Could I ask when you might expect to know how effective Pluvicto has been?

[Scout4answers]

I would check out Mateo Beach's posts on J591 in Perth. He is very open and helpful.

[Hidden]

Enzalutamide has not failed, its the SEs you dont like.

Maybe word it that way to try another "mide"

[CrocodileShoes in reply to Hidden]

Well my PSA has been inching up while on Enza for 6 months, so that's enough for my onco to class it as 'failed'

[Magnus1964]

If you have not been on zytiga yet, you might give it a try. You may not be castrate resistant yet.

[marnieg46]

Have you thought of checking with Michael Hoffman to see if there’s a trial running at Peter Mac or at St Vincent’s in Sydney that might be suitable?

Definitely MateoBeach is the person with whom to connect to if you’re considering Lutetium in Oz. My understanding is that the medical facility that treated him has a base in Sydney which would cut down on cost and time involved in travel from a Melbourne base.

Not much help… but my husband’s MO told him that once Abiraterone fails, lutetium is next cab off the rank. Chemo wasn’t mentioned. He did take Enza for about 8 months when he first became castrate resistant but side effects were simply untenable.

I wish you well in your search for what is the best option for you.

[CrocodileShoes in reply to marnieg46]

Marnie: Is it OK to DM you?

[marnieg46 in reply to CrocodileShoes]

Sure . No problem 😊

[Benkaymel]

Your situation sounds similar in many ways to mine. I'm also on Prostap and Xtandi however in my case PSA continues to drop but the bone mets are stable while some lymph nodes are slowly growing.

I was told originally that I had 4 months to decide if I tolerated Xtandi during which I could switch to Zytiga. After that no option to switch to any other 2nd level hormone therapy drugs and once I came off Xtandi, the next (only?) option is chemo.

Like you, I am not against chemo but I want to be sure it's used when it's most effective. Triplet therapy at the start would have been but that wasn't on offer from the NHS. So now I need to be sure that I'm castrate resistant before chemo and with PSA still falling, I'm not.

I too had a PSMA-PET scan in January which indicated I was likely a good candidate for Lu-177 and since that doesn't require being CR, would like to try that next. I'm hoping that it may become available on the NHS in time for me. Alternatively, I'll have to consider self-paying options.

I wish you the best whatever you choose.

[Ian99]

Hi. We have similarities in our medical history, am also on Nhs. Am mCRPC. If you are having trouble with Xtandi, consider Zytiga, I am tolerating it ok after 18 months. Also you mention your scans show radiographic progression is slow; the question is is it enough to justify chemo; without it chemo can result in you soaking up toxicity and not the tumours. Which is why I have not yet begun chemo. Food for thought. Good luck.

[CrocodileShoes in reply to Ian99]

Hi Ian,

Did you fail Enzalutamide before being placed on Zytiga? My understanding is that there is a 3-month window in which you can change your drug of choice (usually from Enza to Ztiga) after that, the NHS does not allow it.

I don't know why the NHS takes this stance - presumably they believe that if you fail one you'll fail them all - but I know some guys in the US have successfully switched from one to the other.

In my case, I had only just started on Enza when I was rushed into hospital for emergency bowel surgery, and my oncologist told me to stop taking it. This lasted throughout my recovery, (more than 4 months) so I feel like I should have a case to appeal. I'm not hopeful however, and feel that, at this point, being transferred to the Royal Marsden might offer me the best chance of non-chemo options.

If you have sequenced Enza before transferring to Zytiga, please let me know!

Best wishes,

[Ian99 in reply to CrocodileShoes]

No, I was never offered Enzalutamide. I was on Bicalutamide for years. When it began to fail, I started Zoladex injections (ADT), phased out Bicalutamide and began Zytiga. I think you have a case for switching to a medication like Zytiga given your awful experience with Xtandi. I would certainly raise it at Royal Marsden.