What Next After Xtandi Fail?

[ppulatie]

Morning all. Don't post much but now is the time.

Been fighting the Beast since Nov 2016. On Lupron from the beginning and Xtandi since Nov 2019.

Hit Nadir of .21 in Dec 2022. Since then, PSA has been jumping around, but trending upward. End of 2023, it was at .67.

Feb 2024, PSA up to .87.

Yesterday, it was 1.16.

Have Oncology appointment tomorrow. Time to talk what comes next. (We have been expecting this.)

DNA testing is definitely a go. But what comes next? Triple therapy adding Doxy to mix? Or something else?

Must say I did not think I would be considering this till end of year.

[RyderLake2]

Hello,

When ARPI (Androgen Receptor Pathway Inhibitor) drugs like Xtandi start to fail then you have to look at therapies that kill cancerous cells (cytotoxic) rather than just putting them to sleep. Some people have some success switching to an another ARPI drug like Zytiga (abiraterone) which has a different mechanism of action than Xtandi. The most common cytotoxic method is through Docetaxol or chemotherapy. If you are PSMA positive and you can find a clinical trial nearby, there are a number of trials investigating the use of Lutetium-177 a radiopharmaceutical infusion before chemotherapy. Talk to your medical oncologist. Good luck!

[ppulatie in reply to RyderLake2]

Thanks. About what I expected. See oncologist tomorrow.

[God_Loves_Me in reply to ppulatie]

one important note : many times dr will not refer you radiations oncologist.

[Tall_Allen]

Docetaxel can extend Xtandi usefulness:

prostatecancer.news/2022/10...

[ppulatie in reply to Tall_Allen]

Thanks TA. Gonna go over this with Oncologist tomorrow.

[God_Loves_Me]

Base your BIO

May 16, 2024, PSA at 1.15. Trendline appears to be about doubling of PSA every 3-4 months now.

Doubling time is little concerning..

1 How about SBRT radiations if you have mets less than 5

2 Docetaxel - Best results with Xtandi and it will rechallenge the xtandi

source : prostatecancer.news/2019/12...

3 Pluvicto with Xtandi :

prostatecancer.news/2024/04...

4 Xofigo :

prostatecancer.news/2021/02...

5 Clinical Trials of ADC

healthunlocked.com/advanced...

6 immunotherapy drugs

healthunlocked.com/advanced...

[ppulatie in reply to God_Loves_Me]

Thank you. Lots to go over tomorrow with doc.

[Shamrock46]

My husband was on the same treatment. He also had lots of side effects from the Xtandi and at the time his PSA started doubling/tripling at a rapid rate, he began to have mobility problems....getting up from sitting and walking. The Lupron also started affecting his memory. He was offered Abiraterone but chose not to take it due to cardiac problems including cardiomyopathy and an implanted ICD. MO and cardiologist said the drug could land him in the hospital. He was also offered bisphosphonate therapy but that sounded even worse. Since he was prone to SEs, he didn't want to chance necrosis of the jaw which would have meant 2 surgeries....one for the jaw and one for a piece of leg bone to replace the jaw. That seemed a worse solution than the cancer and wasn't guaranteed to help since after ADT the cancer is said to come back more aggressively. He was sick, literally, of all the SEs and chose to stop all treatment in April 2023 with a prognosis of 1 year....and died a few weeks ago on his own terms. Quality of life was more important to him than quantity and he especially didn't want any time in a hospital, choosing palliative care and finally hospice to get him through at home. It's all about what you're willing to endure since every treatment is a tradeoff, but make sure you are an informed patient and understand how much time each choice would provide and at what cost, not just financially but physically and mentally. Most doctors aren't fully honest about all that's involved and hedge their answers with things like "most patients tolerate "x" pretty well." Our MO also told us at the beginning that all the drugs work only until they don't because the cancer eventually outsmarts them all." Good luck!

[Survivor1965 in reply to Shamrock46]

Very sorry to hear this Shamrock. Really sorry for your loss. It was hard to read peace out to you.

[ppulatie in reply to Shamrock46]

Thanks. After 7.5 years, know pretty much what to expect with each treatment and cost/benefit of each. Now it is just what is next.

[j-o-h-n in reply to Shamrock46]

You're such a Lady...

Good Luck, Good Health and Good Humor.

j-o-h-n

[HikerWife in reply to Shamrock46]

Thanks for sharing this. We're only 1.5 years into the journey (stage IV, numerous bone mets), but understand that these types of decisions are in our future. It helps to hear your story. Wishing you comfort and strength. I'm glad your husband had you by his side.

[JJFR60]

More o r less same here. 6 years on Xtandi but PSA started going upwards in march 24.

Started Cabizetaxel (chemo) last week. Had two options , Docetaxel or Cabizetaxel . According to recent studies done at Rotterdam University Hospital Erasmus MC ( my hospital) and one in France , cabi is for effective if in the past Docetaxel has been given as in my case.

So hoping for a good response, only 9 more sessions 😕

[ppulatie in reply to JJFR60]

Good luck

[dhccpa in reply to ppulatie]

Great. Please post a follow-up after your visit. Many of us are on the edge of CR.

[ppulatie in reply to dhccpa]

Will do

[dhccpa]

How about Provenge? See what your doc says about that.

[ppulatie in reply to dhccpa]

On the list

[God_Loves_Me]

may be ARV-766 work if Xtandi fail

2minutemedicine.com/novarti...

[anonymoose2]

No opinions just stating fact. I was on Xtandi and then put on Zytiga. My numbers came down. Good luck! 🙏

[God_Loves_Me in reply to anonymoose2]

How many months did you took Xtandi ?

[anonymoose2 in reply to God_Loves_Me]

26

[ppulatie in reply to anonymoose2]

52 right now

[j-o-h-n]

Hope all goes well with your M.O. appointment.

Good Luck, Good Health and Good Humor.

j-o-h-n

[ctflatlander]

I'm in the same boat. 80yo started 2017, Lupron, Zytiga, debulked the prostate, orchiectomy, psa rising to .82 I'm going for scans nest week and considering triplet w/Xtandi. Good luck with your decision. Bob

[ppulatie in reply to ctflatlander]

We decided today to just keep checking PSA every 6 weeks and make treatment decisions based upon current tests. Then at some point change medications dependent upon how I am responding.

[God_Loves_Me in reply to ppulatie]

Tell us more about question you discussed.

[Seasid]

Niclosamide and Bicalutamide Combination Treatment Overcomes Enzalutamide- and Bicalutamide-Resistant Prostate Cancer

Chengfei Liu; Cameron M. Armstrong; Wei Lou; Alan P. Lombard; Vito Cucchiara; Xinwei Gu; Joy C. Yang; Nagalakshmi Nadiminty; Chong-xian Pan; Christopher P. Evans; Allen C. Gao

aacrjournals.org/mct/articl...

[God_Loves_Me in reply to Seasid]

Tall_Allen do you recommend this combination?

[Seasid in reply to God_Loves_Me]

More info:

Therapeutic Approaches to Targeting Androgen Receptor Splice Variants

ncbi.nlm.nih.gov/pmc/articl...

[God_Loves_Me in reply to Seasid]

Thank you , does dr prescribe Niclosamide and Bicalutamide ?

[ppulatie in reply to God_Loves_Me]

Did Bicalutamide. Got 10 months. Then switched to Xtandi.

[Seasid in reply to God_Loves_Me]

Some clinical trials for Niclosamide. You could understand better the drug and hopefully there are some results.

clinicaltrials.gov/search?t...

[Seasid]

No it is very toxic

[Seasid in reply to Seasid]

NiclosamideWithin the landscape of existing therapies and compounds undergoing clinical trials, several avenues hold promise for directly targeting AR-Vs. A notable contender is niclosamide, which exhibits potent inhibitory effects on AR-V7. Niclosamide’s mechanism of action for prostate cancer is expected to involve hindering AR-V7 recruitment to androgen-responsive elements such as the PSA promoter and curbing its protein expression by instigating degradation [16]. Furthermore, preclinical data suggest this compound demonstrates proficiency in curbing prostate cancer cell proliferation in vitro and mitigating tumor growth in vivo [16]. Notably, niclosamide not only overcomes resistance to enzalutamide but also synergizes with enzalutamide therapy, thus portraying its potential utility in advanced prostate cancer cases, particularly those resistant to enzalutamide [16].

The therapeutic trajectory of niclosamide encountered hurdles in 2018 during a Phase I dose-escalation study testing oral niclosamide plus standard-dose enzalutamide in men with mCRPC previously treated with abiraterone (NCT02532114). The trial revealed that the doses needed to attain efficacious plasma concentrations yielded substantial toxicity, precluding the viability of niclosamide as an oral anticancer agent. Consequently, the trial was prematurely halted due to futility, casting uncertainty over the future development of niclosamide as a cancer therapy due to its poor pharmacokinetic properties [17].

Fortunately, further research has been conducted to establish the maximum tolerable dose and recommended dosage of niclosamide. A Phase Ib trial investigating reformulated niclosamide in tandem with abiraterone acetate and prednisone in men with CRPC elicited findings that underscored the combination’s favorable tolerability profile and the achievement of therapeutic niclosamide concentrations (NCT02807805). Encouragingly, select patients recorded noteworthy declines in PSA levels, coupled with radiographic ameliorations. The findings suggested that the combination of niclosamide and abiraterone is clinically active [18]. Phase II of this trial is ongoing.

A recent investigation has endeavored to amend niclosamide’s poor pharmaceutical properties by analyzing the efficacy of a novel series of niclosamide analogs and further characterizing the structure-activity relationship of the compound. Several analogs exhibited equivalent or improved anti-proliferation effects in cell lines, potent AR-V7 downregulation, and improved metabolic activity [19]. Further investigation into the clinical use of these compounds may yield exciting results for the field

[Seasid in reply to Seasid]

Niclosamide Wikipedia

en.wikipedia.org/wiki/Niclo...