Dad is going to start ADT shortly. He has bone mets
One MO said to start with Zoladex and after two weeks to add xtandi ( starting 40 mg )
The other MO says to start only Zoladex and will think of xtandi or zytiga later at some point , maybe when Zoladex starts being less effective. He says if we use all bullets at once what will we do later ?
Which one is the better option as per experiences here ?
Both dismiss chemo at this age
The idea of sequential therapies is right up to date to 10 years ago. So let's update ourselves.
Massive clinical trials (CHAARTED, STAMPEDE, ARASENS etc. etc.) have all shown that piling up two or even three therapies up front gives demonstrably longer life expectancy. The old way was try one therapy, and it fails, and then try another therapy, and it fails etc etc.
Difference between the new way and the old way is measured even possibly in years.
The argument about "if we use all bullets at once what will we do later?" is not logical. You're not using all bullets at once. You're using (1) ADT, plus (2) an AR antagonist (Xtandi, which is enzalutamide) or an ARPI (also known as an ARAT, Zytiga, which is Abiraterone) - together these two types of med, ADT + one of an AR antagonist or an ARPI, is called doublet therapy and (3) if we add Docetaxel chemo, that makes it triplet therapy.
What happens after the likely failure of even triplet therapy is a bit of an unknown. It's still likely to be longer than individual therapies all together. But there are developing protocols on what has been labeled "re-challenge", after failure of modern public therapy. That's just one modality.
What the trials seem to show is that combination therapy up-front has significantly better results then the same therapies taken sequentially.
I am not advising you that this is appropriate because depending on the stamina and health of your Dad, these programs may or may not be appropriate. We are assuming metastatic PCa.
For the record, and despite the clinical trials, triplet therapy is not standard of care yet worldwide and even everywhere in North America. But there was no question about the implications of the clinical studies. Doublet therapy however is widely accepted and adopted.
And there's lots to read here on the forum and for searching on Google all about this.
After a diagnosis of metastatic prostate cancer one is overwhelmed. And it's hard to figure out if your doctors are up to date or not.
Thank you 😊🙏🏻
I re-edited it again.
Thanks much for your generous help
so one question comes to mind. If one is going to do both generation ADT which would hopefully keep testosterone and psa down , does it then matter much if one does Firmagon or an agonist - from the therapy point of view - I understand there may be other safety benefits though
I don't think so but Tall Allen it would provide a better answer. Aside from the other questions about side effects, which are still a little debatable, I think either agonist or antagonist ADT both are good.
Excellent explanation.
Great input! Really superb! I really appreciate when people give both generic and brand names. This especially helpful to novice posters. It is important to remember this is like learning a new language in a compressed time frame.
Thank you again for taking the time to do this.
I already mentioned several times that you have to add second generation ADT when there are bone mets. E.g. Enzalutamide or Apalutamide which could be called "Super-Bicalutamides".
Agree with doing both. Husband was put on just bicalutumide last year (a mono treatment) but it was ineffective and PSA started to rise. Now on quarterly Lupron and Erleada (apalutumide) since January. Responding to this much better and PSA declining quickly. Also maybe given his age (78) his MO not starting any chemo yet though we have asked about it. He has six bone Mets and latest scan showed improvement after the doublet therapy to date.
Whether your husband will live longer when a chemo is added is unknown. It has been shown in trials that the triplet therapy works better than ADT alone. But the trials were not designed to compare doublet therapy against triplet therapy. I would get Pluvicto when the combination stops working. By that time Pluvicto will be approved to be used earlier in the disease course.
Thanks. My father 😊
Tall Allen , would appreciate your comments here please
ARASENS used Darolutamide (Nubeqa) as ARSi. I am following that protocol, I have read that darolutamide does not cross the brain-blood barrier, so it should give less side effects in terms of possible seizures, brain fog and so on. In my case that is true, but I cannot compare to others.
"... I have read that darolutamide does not cross the brain-blood barrier, so it should give less side effects in terms of possible seizures..."
Have you found a source for that statement? I have found blood:plasma ratios for Xtandi and Erleada (27% and 62% ), but not for Nubeqa. My urologist said it was 19%. I do see these statements that do indicate some penetration of the brain:
"Darolutamide is a structurally distinct AR inhibitor with low blood–brain barrier penetration." ncbi.nlm.nih.gov/pmc/articl...
"Darolutamide... is associated with low penetration of the blood–brain barrier..." nature.com/articles/s41391-...
"... darolutamide does not cross the blood-brain barrier well..." targetedonc.com/view/next-g...
"Advise patients of the risk of developing a seizure while receiving NUBEQA." nubeqahcp.com
pubmed.ncbi.nlm.nih.gov/328....
anyway, on that aspect it looks much better than the others on paper
Yes, and I wish I could get it without chemo docetaxel. Nubeqa is only for PCa "in combination with docetaxel, OR that has not spread to other parts of the body and no longer responds to medical or surgical treatment that lowers testosterone (nmCRPC)." nubeqa-us.com
I strike out on three counts: I have spread, am responding to the doublet of Orgovyx and Abiraterone, and so am still CS.
I thought you could use it also in doublet with metastatic cancer
I initially wanted my doublet to be ADT plus Nubeqa for the BBB reason. But Nubeqa says no to doublet ( I added their link to my previous post), and my doctor said no. So I chose Abiraterone. And yet, I hear of many people taking Nubeqa in doublet.
agree with MO
One MO said to start with Zoladex and after two weeks to add xtandi ( starting 40 mg )
it would scare me if my MO did not at least discus the fact that adding a second agent early prolongs life. I think I would consider looking around. I think triplet therapy is also SOC in someone with detectable Mets. I would have liked to hear a discussion of this approach as well and why he did not like it for your father.
Dad is 83. They said at this age chemo can be very rough to handle
That probably depends on his individual health situation. Does he have cardiovascular issues, pulmonary or diabetes issues, or high BP? If not, he may do well on it. But you must assess.
I had 9 rounds of Jevtana at age 82…No problem….No hair loss or nausea….Started with 6 rounds which was no problem… My oncologist said let’s try 4 more..,,,After 3 more we stopped as my numbers were getting low…,But 6 was a breeze..,,,1 hour in the chair every 3 weeks..,
Thanks for sharing. What was your initial diagnosis?
I’m not as savy as most on this forum so I’ll tell you best I can…,My PSA was 194 and my PC had spread to 3 or 4 bones (ribs) and as I remember a couple other places….I was immediately put on Lupron (terrible crap) and did the Jevtana at the same time…Kept getting Lupron for 4 years….PSA stayed down but no energy, no libido, just surviving…yes those drugs keep you alive but QOL was zero for me…about 8 months ago I started BAT and stopped ADT (Lupron) a man needs testosterone..,,What a turnaround!,,,,Of course my PSA went up…At this stage of my life (now 86) I just want to feel good.,,last labs (2 weeks ago) PSA was 124…So what?…I feel pretty darn good.., The plan is starting Pluvicto in early July right after our bucket list cruise to Alaska in 2 weeks.,…..Then, when PSA goes down re enter BAT..,,Then when PSA goes up, stop and do Xtandi or some other drug to get the PSA down again so we can add BAT back in….I will never take another shot of Lupron again…I’m just not going to do anything just to stay alive…QOL is more important to me.,..Good luck in whatever direction your dad wants to go….
thank you. I hope you will continue feeling good and do all you want to 😊. What is BAT ?
We are on a cruise to Alaska in two weeks too! Enjoy as the scenery sounds simply incredible. This is why we are working so hard to stay above ground!
PS. We are awaiting the final results this fall of the PATCH trial which compares using estrogen instead of drugs like Lupron over a lengthy period of time for both QOL and mortality.
I guess if I was 60 or 65 I’d be trying anything…understandably so…but at 86 the clock is ticking and QOL is #1 priority for me…Patch sounds interesting…I’ll check it out…Thanks for the heads up..
Google “Bryce Olson ..a patients story” watch the vid and read the story…BAT basically is big doses of testosterone given ever 28 days…,also just google “High doses of testosterone for metastatic prostate cancer”..,,lots of info ….Unfortunately.Bryce passed away last year, but he never gave up and wasn’t afraid to try something new…and that’s how I feel.,,,Been dealing with this crap for over 10 years now..,.
Thank you. I will see it 🤗.
We have been looking into that too. My brother in law may be trying that.
I've been matastic for over 8 years and kept it completely under control with only 1st-generation intermittent ADT. The first four years, Lupron anda Casodex, then four years ago I discovered degarelix (Firmagon brand in the U.S., I think) and found it to cause much less severe side-effects yet keeps my PSA under control and lymph nodes from swelling with only 3-4 1-month injections per year. Even though a lot of recent research shows that zapping it with 2-3 different meds can indeed extent life, for me at 76 years old and already 20 years since I first disccovered PCa, the issue of side-effects ad quality of life have been paramount, so I've refused other treatments even when recommended by my doctor.
So you took Casodex for 4 years ? Nowadays doctors usually add a newer lutamide like xtandi etc and give the Casodex only for some days to prevent the Lupron testosterone surge. Was it your choice to remain on Casodex which is milder or the doctors ? I am asking as earlier the plan was to give Lupron to my dad who is 83 and the doctor wrote a prescription for 3 weeks of Casodex to be taken before the lupron.
But then after reading over here a lot we decided to go with relugolix as it is available here in India and seems to be safer for the heart.
Have consulted 2 medical oncologists - one said to discontinue Casodex and after two weeks to add 40 mg xtandi to the ongoing relugolix and another MO said to continue the Casodex for a month
Overall I like the first MO more so have discontinued the Casodex since 3 days which is when he started the relugolix
Would love to hear your thoughts
Dad has bone mets
Well, if your dad has bone mets, that complicates things, for sure. But no, the Casodex was my decision, not recommended by my doctors who continuously pushed me to get Lupron shots. However, after my PSA had shot up to 47 and a swollen lymph showed up in a PET/CT scan, I did Lupron plus Casodex for six months, at the end of which my PSA dropped to 0.03 and the lymph gland returned to normal. The side effects from that were so hideous (particularly hot flashes, heart palpitations, and depression) that I refused treatment for a full year. At the end of that year, my PSA had climbed up to 5.4 and the doctor really pushed me to start Lupron again, but I refused and told him I would only do Casodex till the PSA dropped again, then take a break till it climbed again. Generally, I took it only 2 weeks to a month at one time, then a break for 2-3 months. I continued this for about 2 years, when the Casodex quit working, then went back to Lupron until I discovered degarelix.
Yes, regulolox and degarelix both (called antagonist, vs agonists like Lupron) are much safer on the heart. On Lupron, my palpitations got so bad they showed up on an EKG so my family doc referred me to a big university hospital for heart tests, and the doctor there, who was also the department head said heart, veins, and arteries were in great shape, on problems at all. Now 4+ years on degarelix, I have only rare palpitations but have had those all my life. Hope this helps.
Stopping docetaxel at just 4 per Dr - good move or not?
PSA rise on Xtandi
Wait time for radiation is 6-8 weeks in BC Canada; will this cause an issue with triplet approach?
Making the Best CHOICE for Daddy. What to do next.....
Meeting with our oncologist for castrate resistance metastatic prostate cancer 
