Casodex after castration resistance?

[Nestorian]

After being undetectable on mono HT (Zoladex) for 67 months my dad's PSA started climbing in December 2022. In March it was 0.05. His testosterone level also rose from 0.6 to 1.2. The doctor recommended to add Casodex. After a month, in April his PSA was 0.024 and testosterone was 0.9. I have two questions:

1) How relevant is using Casodex at this stage? Wouldn't it negatively affect the effectiveness of Enzalutamide when/if my dad will have to use it in future considering they act using similar mechanisms?

2) Are those fluctuations in the level of testosterone normal for someone being on Zoladex for several years? Does it lose its effectiveness with time?

Thank you!

[GP24]

Casodex in this situation is old fashioned and not effective. You have to add Zytiga or Xtandi now.

[Tall_Allen]

There's nothing in your profile, so your questions are unanswerable. What is his situation? Has he been treated and recurrent? Metastatic? Was Zoladex his first and only treatment?...

[Nestorian in reply to Tall_Allen]

Sorry. My bad. Now I see the post is very vague. He was diagnosed with adenocarcinoma, PSA 11, GS 9. Clear bone scan. Had open RP. Three months after surgery his PSA was 0.4 and increasing. PET CT showed 1 spine met and a pelvic lymph node. Had full pelvic radiation and SBRT for spine and put on Zoladex. Went undetectable after one month. 5 years later psa became detectable (0.009) and gradually reached 0.05. Thanks for replying.

[Tall_Allen in reply to Nestorian]

Thanks - that background helps. His PSA is still very low, but that is at least partly due to the treating the spine met. There are more (invisible for now) where that came from. I believe the evidence leans towards hitting the invisible, micromets hard and fast with more intensive hormone therapy than just Zoladex. Adding Casodex is one step up, but adding one of the second generation hormonals (Zytiga, Xtandi or Erleada) may do a better job of setting the micromets back for a longer time. Castration resistance is delayed longer by using the stronger medicines.

Zoladex never stops suppressing testosterone.

[Nestorian in reply to Tall_Allen]

Thank you. Judging by your experience and knowledge could this rise of testosterone (from 0.6 to 1.2) lead to the rise of PSA or is it just an insignificant fluctuation and BCR is due to castration resistance? And is it normal for testosterone level on HT to go up after 5 years?As for Casodex the doctor recommended it because where we live second generation hormonals are not covered by insurance. That's why I wondered whether we could use it for some since it seems to be working. But what is worrying me is couldn't using Casodex lead to the resistance to all types of -lutamides that block the receptors and prevent him from using Xtandi (out of pocket) in future?

Sorry for asking so many questions. And thanks again for answering.

[Tall_Allen in reply to Nestorian]

That's still very much in the castration level.

There is no BCR - PSA is very low.

If you can't get a 2nd gen hormonal, you don't have a choice.

[j-o-h-n]

Ps. Dad's Age and Location?......update his bio.... all info voluntary - Thank you and him and good wishes to your Dad and to you....... keep posting!!!

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 05/07/2023 9:16 PM DST

[Nestorian in reply to j-o-h-n]

Thank you! He's 68. We live in Russia.

[RusLand in reply to Nestorian]

Hello, Nestorian! For me, as a person living and undergoing treatment in Russia since 2016, it is very strange to read that you cannot get all modern medicines under the Compulsory Health Insurance system..?! Absolutely all second-generation antiandrogens are available under the CHI and moreover, our insurance policy, unlike many countries, does not have a limited amount! You can be treated as much as you want and with any drug that a medical consultation will prescribe to you! Also with all high-tech research, including PET/CT and all genetic studies of HRR genes by the NGS method can be done for free without spending a cent on it. Since last year, in Moscow, at the Blokhin Center and at the Institute of Radiology in Obninsk, it is possible to undergo PSMA therapy using the Lutetium isotope (177Lu). Write to me in private messages and I will teach you how you can and should be treated by CHI in Russia! Good luck to your dad! And God bless us all!

[j-o-h-n]

Spasibo. Bud' zdorov.

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 05/08/2023 1:16 PM DST

[Nestorian in reply to j-o-h-n]

Spasibo dorogoi!

[RusLand]

Regarding your question.. Yes, there is an opinion among some specialists that taking Bicalutamide in the future may reduce the therapeutic effectiveness of second-generation antiandrogens, but no studies have been conducted on this! As well as there was no direct comparison of Bicalutamide with second-generation antiandrogens! In the ENZAMET study, there was an attempt to compare Enzalutamide with first-generation antiandrogens, but there was a cocktail of first-generation antiandrogens without revealing the exact proportions! But even in these studies funded by the manufacturer of Enzalutamide, they were forced to admit that in terms of the frequency of adverse events of the 3rd and 4th degrees, Enzalutamide irrevocably lost to first-generation antiandrogens. It is also necessary to understand that absolutely all second-generation antiandrogens were approved for use based on comparative studies, second-generation antiandrogens + ADT were compared with placebo + ADT. In fact, ADT was compared with ADT + antiandrogens of the second generation. All these studies are indicated in the instructions for these drugs! For example, in the PREVAIL study, the overall survival in the study interval was 32.4 months for the ADT + Enzalutamide group and 30.2 months in the ADT group. And we must also understand that all studies with second-generation antiandrogens were funded by the manufacturers of these antiandrogens!

In this context, of greater interest is this study, where the manufacturer of the new drug TAK-700 (Orteronel) risked a direct cut with Bicalutamide and lost in the III phase of its trials, where Bicalutamide demonstrated 70 (!) months of overall survival: ascopubs.org/doi/abs/10.120... I find on this forum many people who have been treated with Bicalutamide for more than 5 years and a personal record here, if I'm not mistaken, it is 13 years old! And I personally am very interested in what is the record for Enzalutamide...