1. < Prostate Cancer

Adverse effects of ADT for aggressive tumors

Posted by hanscasteels @hanscasteels, 6 days ago

Quick question - it’s been nagging me for a while and would appreciate any insight. In my case, I have a PSA reading of 25, a small, aggressive but apparently contained tumor, that has grown in a naturally low testosterone environment. My hypothesis is that therefore, given the limited testosterone availability, this tumors has found alternative pathways or is producing its own testosterone, thus leading to the high PSA readings. Apparently it also shows cribriform cells together with perineural invasion. If this hypothesis is correct, would the administration of Firmagon not be counterproductive to the objective of lowering testosterone, instead accelerating the environment that this tumor has grown in naturally, making it even more aggressive? If that’s plausible, are there countering strategies I should be thinking about? My oncologist is a nice dude, but seems to have issues thinking outside the dogma box

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northoftheborder | @northoftheborder | 4 days ago

I don't remember your exact situation, @hanscasteels , but as I understand it, if the tumour is still contained fully in your prostate (non-metastatic) and responds to ADT (castrate-sensitive) — aka "nmCSPC" — then I think it wouldn't be normal to prescribe a lutamide or other ARSI in addition to the ADT, but that might have changed recently.

Apalutamide is approved in Canada for two situations:

1. non-metastatic castrate-resistant prostate cancer (nmCRPC), where the cancer hasn't metastasised yet but has stopped responding to ADT.

2. metastatic prostate-sensitive prostate cancer (mCSPC), where the cancer has metastasised, but is still responding to ADT.

In the TITAN trial, I think they continued Apalutamide after progression from mCSPC to mCRPC (metastatic castrate-resistant prostate cancer) and that it still showed benefits, but it's not recommended to start on it if you already have mCRPC — there are other lutamides approved for that.

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1 reply
hanscasteels | @hanscasteels | 4 days ago
In reply to @northoftheborder "I don't remember your exact situation, @hanscasteels , but as I understand it, if the tumour..." + (show)
@northoftheborder

I don't remember your exact situation, @hanscasteels , but as I understand it, if the tumour is still contained fully in your prostate (non-metastatic) and responds to ADT (castrate-sensitive) — aka "nmCSPC" — then I think it wouldn't be normal to prescribe a lutamide or other ARSI in addition to the ADT, but that might have changed recently.

Apalutamide is approved in Canada for two situations:

1. non-metastatic castrate-resistant prostate cancer (nmCRPC), where the cancer hasn't metastasised yet but has stopped responding to ADT.

2. metastatic prostate-sensitive prostate cancer (mCSPC), where the cancer has metastasised, but is still responding to ADT.

In the TITAN trial, I think they continued Apalutamide after progression from mCSPC to mCRPC (metastatic castrate-resistant prostate cancer) and that it still showed benefits, but it's not recommended to start on it if you already have mCRPC — there are other lutamides approved for that.

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Three different scan don’t show metastasis, but that doesn’t mean it isn’t lurking somewhere. I am starting on Firmagon this week (it only took three weeks to get this going for heaven’s sake). Next is figuring out when to start considering alternatives or complementary services. Given the track record of the “professionals” here… might be an interesting conversation of me trying to convince those that think they own the universe (at least they behave that way)

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shelby29 | @shelby29 | 4 days ago
In reply to @northoftheborder "All great information. I'll just add that the second generation ARSIs (the so-called "-lutamides") have had..." + (show)
@northoftheborder

All great information. I'll just add that the second generation ARSIs (the so-called "-lutamides") have had stunning results for situations where they're tested and approved, both for delaying castrate resistance and for delaying progression after castrate resistance.

In my layperson's opinion, the main reason still to take a first-generation 30+-year-old ARSI like Zytiga would be either that you live outside the U.S. and there's no -lutamide approved yet for your cancer situation, or you live in the U.S. and your insurance will pay only for the older stuff (which is out of patent, and thus much less expensive).

Here in Canada, at least Apalutamide, Enzalutamide, and Flutamide (maybe more) have Health Canada approval, though Enzalutamide's approval was just last year, so it might not be in the provincial formularies yet.

I've been on ADT + Apalutamide (Erleada) for mCSPC since 2021, and consider it my miracle drug. 🙂

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I was taken off zytiga after 11 months because I suffered a heart attack. (Gleason 8 with cribiforms, stage 3tb)
Do lutamides affect the heart like zytiga?

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2 replies
northoftheborder | @northoftheborder | 4 days ago
In reply to @shelby29 "I was taken off zytiga after 11 months because I suffered a heart attack. (Gleason 8..." + (show)
@shelby29

I was taken off zytiga after 11 months because I suffered a heart attack. (Gleason 8 with cribiforms, stage 3tb)
Do lutamides affect the heart like zytiga?

Jump to this post

Prolonged QT interval is a rare but observed side-effect for Apalutamide, at least. I don't know how it compares to Zytiga, heart-wise, but at least you don't have to take a steroid with it, which might be helpful.

It would be a good question to ask both your oncologist and your cardiologist

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northoftheborder | @northoftheborder | 4 days ago
In reply to @hanscasteels "Three different scan don’t show metastasis, but that doesn’t mean it isn’t lurking somewhere. I am..." + (show)
@hanscasteels

Three different scan don’t show metastasis, but that doesn’t mean it isn’t lurking somewhere. I am starting on Firmagon this week (it only took three weeks to get this going for heaven’s sake). Next is figuring out when to start considering alternatives or complementary services. Given the track record of the “professionals” here… might be an interesting conversation of me trying to convince those that think they own the universe (at least they behave that way)

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I'm sorry you're having a bad experience with your current onco team.

I know you're concerned about delays, but you wouldn't have to pause your current treatment in K-W while you looked into transferring it to Princess Margaret in Toronto, which (as others have mentioned) is one of the top-ranked cancer centres in the world, and just over an hour's drive away from K-W (traffic permitting).

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jeffmarc | @jeffmarc | 4 days ago
In reply to @northoftheborder "All great information. I'll just add that the second generation ARSIs (the so-called "-lutamides") have had..." + (show)
@northoftheborder

All great information. I'll just add that the second generation ARSIs (the so-called "-lutamides") have had stunning results for situations where they're tested and approved, both for delaying castrate resistance and for delaying progression after castrate resistance.

In my layperson's opinion, the main reason still to take a first-generation 30+-year-old ARSI like Zytiga would be either that you live outside the U.S. and there's no -lutamide approved yet for your cancer situation, or you live in the U.S. and your insurance will pay only for the older stuff (which is out of patent, and thus much less expensive).

Here in Canada, at least Apalutamide, Enzalutamide, and Flutamide (maybe more) have Health Canada approval, though Enzalutamide's approval was just last year, so it might not be in the provincial formularies yet.

I've been on ADT + Apalutamide (Erleada) for mCSPC since 2021, and consider it my miracle drug. 🙂

Jump to this post

After my fourth reoccurrence, I was put on abiraterone. It Only got my PSA down to undetectable one time in 2 1/2 years but for 2 1/2 years it did not fail me and gave me 2 1/2 more years of very low PSA numbers before I moved onto Darolutamide.

With someone who has had reoccurrences it’s just a matter of time before the drug they pick (Zytigaor a lutamide) stops working, That’s the one thing we all face if you have advanced prostate cancer. Your cancer will eventually defeat the drug you are on and you have to move on to something different. I may get four years on Darolutamide Before my PSA starts to rise again, But Zytiga gave me another 2 1/2 years since I started with it. Very unlikely Darolutamide will work for 6.5 years. That is a hypothetical, Darolutamide May not last me four years, but whatever amount of time it gives me zytiga gave me 2 1/2 more years without reoccurrence.

Yes, the side effects of Zytiga aren’t desirable, but going there first can give more time before stronger measures are needed.

Then there is the Lancet article I have posted many times that recommends the best sequence is Zytiga followed by a lutamide.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30688-6/abstract?mc_cid=c2dca8aa74&mc_eid=99575fc699

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northoftheborder | @northoftheborder | 4 days ago
In reply to @shelby29 "I was taken off zytiga after 11 months because I suffered a heart attack. (Gleason 8..." + (show)
@shelby29

I was taken off zytiga after 11 months because I suffered a heart attack. (Gleason 8 with cribiforms, stage 3tb)
Do lutamides affect the heart like zytiga?

Jump to this post

I should add some personal experience. For two months in 2022–23, it was mistakenly thought that I'd had a heart attack at some point in the recent past (presumably in the wake of my emergency surgery and post-surgical complications in 2021), until further tests and a review of the original TTE imagery reversed the verdict.

During those two months, they did not take me off Apalutamide, or even float the idea that staying on it might be an issue.

Your mileage may vary.

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shelby29 | @shelby29 | 4 days ago

Heart attack happened 11 months after starting Eligard. Had 3 stents placed, then 5 months later triple bypass. Have an appt with cardiologist in a couple weeks and will ask about whether this drug is safe for me. They have me on Eligard for 3 years, so 1 year left.

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