Pluvicto plus Xtandi

[Rondief]

A question for Tall_Allen, j-o-h-n, LearnAll, tango65 and a lot of other guys smarter than me.

In Aug 2019 I had a Radical prostatectomy. Nov 2019 I was dx with mCRPC and 6 bone lesions throughout my body. 

I’ve run the gambit of Bicalutamide, Docetaxel, Abiraterone, Cabazitaxel, still taking Lupron and Zometa. 

At the beginning of June I started Enzalutamide (Xtandi) 4x40 mg. After about a month I started having issues with fatigue, loss of appetite, nausea and dizziness.

On July 7 I called my doc and stopped taking Xtandi and I started feeling better a few days later.

On July 12, yesterday, I had my first Pluvicto (lutetium Lu 177) treatment and other than a little nausea and fatigue I feel fine. 

Here’s my question, my oncologist wants to re-start me on the Xtandi at a 2x40 mg rate. Does this make sense?

Thanks in advance for everyone that responds.

[Tall_Allen]

The ENZA-P trial in Australia hopes to find the answer (with full dose Xtandi), The rationale is that Xtandi may increase ('upregulate") PSMA expression:

ascopubs.org/doi/abs/10.120...

[Rondief in reply to Tall_Allen]

Interesting that there could be some synergism. I already know that my body can’t handle the 160mg. I lost 15 pounds in one month and blacked out a couple of times from dizziness and fatigue. So I guess 80mg is definitely worth a shot if my body can handle it.

Thanks for the link and your thoughts.

Ron

[Shooter1 in reply to Rondief]

80 mg held mine in check for about 3 yrs. Still on it but may soon drop it.

Stopped end of July and started BAT on Aug 13. 400 mg of T-cyp in the gluteus maximus, Very easy to self administer. Life Is Good, even with a needle in you hand..

[Seasid in reply to Shooter1]

What will you take after dropping Xtandi? Why are you dropping Xtandi?

[Shooter1 in reply to Seasid]

Multiple progressions in bone mets even with radiation therapy while on xtandi. First mets zapped and held for 7 mo. with nice drop in PSA, then back with rising PSA. Zapped again and just stabilized for a couple of months. Hit them with Xofigo and the old mets stayed stable, but got 4 new ones in a 4 mo. period. Got to do something else. What????

[Seasid in reply to Shooter1]

Start a new post with this question. We can then think about, reply and you can then ask couple of oncologist for opinion. Detail everything i your post. István

[Seasid in reply to Shooter1]

And list clearly (less is more) wich treatments you had until now. I believe you didn't have chemotherapy yet? Your PSA is still very low. You see all of this only on PSMA PET scans? It is still very low volume?

[Seasid in reply to Seasid]

How about your blood work? Is it good? Usually they stop treatment when the bloodwork is out of range to much. Do you have bone pain? Are you getting bone medication? (I believe yes, otherwise they would not give you Xofigo.

[Seasid in reply to Shooter1]

I read carefully again your profile. Do you take bone strengthening medication? With Xofigo parallel you could have chemotherapy. I don't know how good is your blood work, but I hope that chemotherapy was also considered for you by the oncologists. After chemotherapy Enzalutamide or similar drugs (Abiraterone with Prednisone) could maybe work again and better. I am not a doctor but that is what I read on this forum. Therefore ask your oncologist to add chemotherapy (20mg/m2 of Jevtana is milder) to Xofigo. You can always stop chemotherapy treatment if you develop side effects. I hope that you are receiving denosumab for your bones. You are receiving too much local therapy what may not be helpful. You should only receive radiation and Xofigo if you have bone pain. You should focus more on systemic treatments. My oncologist professor Joshua said to me that Xofigo is good for the bones but it is not helping with the cancer. You should have chemotherapy if your PSA doubling time is rapid. Chemotherapy is effective for rapidly growing cancer. István

[Rondief in reply to Shooter1]

That’s great, I’m hoping for the same

[Seasid in reply to Tall_Allen]

Thanks, it is interesting.

[tango65]

it is not a bad idea since enzalutamide increases the PSMA expression in patients with mCRPC:

pubmed.ncbi.nlm.nih.gov/342....

[Seasid in reply to tango65]

And may eliminate or minimize the repopulation possibility with the PSMA negative cancer.

[Seasid]

Try to take the full dose of the Enzalutamide at least during the Lutetium PSMA therapy in order to avoid repopulation etc. Maybe your body will adjust to the medication. Try to increase it slowly and be extremely careful to avoid falls and injury. Enzalutamide is crossing the blood brain barrier and therefore has an effect on the CNS.

[Seasid]

Check the other drugs what you are taking with the hospital pharmacist for interference (compatibility) with Enzalutamide. I dropped all my none essential medication and supplements in order to prepare myself for Enzalutamide. Later I may reintroduce my none essential medication one by one. A drug holiday is a good thing if you have collected to take lot of none essential medication. I stopped statins, aspirin, metformin and now experimenting to stop my high blood pressure medication. I have sleep apnea and I am trying to improve that. I am still not taking Enzalutamide. You may actually need some high blood pressure medication with Enzalutamide. Do you have a blood pressure monitor? Do you have a PCP to help you on the day by day basis if you need medical advice?

[Rondief in reply to Seasid]

Seasid, I do have high blood pressure. I am taking 20mg Lisinopril daily. My BP Ron’s in the 120’s/70’s. I also take calcium daily and Omeprazole occasionally for acid reflux. I did check with the hospital pharmacy and none of those interfere the the Enzalutamide.

If I can 2x40 after a month I’ll consider increasing it but the 4x40 kicked my a$$. It was a case where the treatment was worse than the disease.

That for the insight,

Ron

[Seasid in reply to Rondief]

Wow. Your blood pressure is perfect. My goes up to 150 /90 and i feel better then when it is 120/70. I believe it only occasionally goes up. You can ask for a 24 hour blood pressure monitor from your pathology.

Allen Edel said one time that Enzalutamide should be taken the full dose, otherwise you are experimenting on yourself. I agree that you need to be careful when you are increasing the dose. Your body will hopefully adjust to the medication. I also taking occasionally proton pump inhibitors like you. I don't drink alcohol, stopped smoking and stopped drinking coffee in order to sleep better. I still drink hot chocolate, so I am still not cofein free. It is very important to take Enzalutamide during the Lutetium PSMA therapy. That is my personal interpretation.

[Seasid in reply to Rondief]

What would be your blood pressure without your high blood pressure medication? Can you ask for 24h blood pressure monitor? I checked the normal range for blood pressure for my age and it is under 145/90 . I wouldn't mind if occasionally goes even up to 160/90 during the day. I believe that lower blood pressure for older people can cause falls and that you don't feel well. I personally think that my biggest problem is my salt intake. If i could avoid salty food and if i could eat food with lot of arginine than I could keep my blood pressure under 150/90. I realized that after walking and phisical activity my blood pressure is normal. My blood pressure goes up when I am resting and my heart rate gos down to 57 per minute. I believe that your blood pressure medication could be causing that you feel bad. I am not a doctor but i don't believe that I could lower my blood pressure to 120/70 without side effects. My heart was checked by the heart specialist and he said that except some minor age related changes my heart is good. He wanted to put me on Betta blockers and calcium channel blockers because of some none life threatening arythmyas. I fletly rejected that drugs and stayed with perindopril arginine.

[Rondief in reply to Seasid]

I was dx with hypertension 170/120. We started at 10mg and it came down to 150/100. Through first and exercise 20mg has kept me at 120/70 range

[Seasid in reply to Rondief]

Did you check yourself for sleep apnea? It is not uncommon. You need to have an overnight sleep study in a hospital. I stopped breathing every two minutes for more than 10 seconds. I am using CPAP Resmed S9 with 9cm H2O2 pressure setting now.

[Fiddler2004]

Yes. Xtandi website lists 1/2 (80mg) dose as an option for those of us who've had adverse reactions at full dose. 🙏

[Seasid in reply to Fiddler2004]

That is good to know. Thanks.

[j-o-h-n]

To Rondief,

Asking me is like asking a guy going deaf what are the symptoms, and he replies "It’s a TV show about a little yellow family...but what has that got to do with my problem?"

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 07/14/2022 2:51 PM DST

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

Thanks for the chuckle. You know j-o-h-n, sometimes that’s just what the doctor ordered,

[Seasid in reply to Rondief]

My sister is a doctor. They are not God. My grandmother altered the doctors order in order to suit her, and she lived 89 years long. She could live longer, but developt heart failure, but her son was drunk and didn't take her to the hospital. You still need doctors and you should have regular access to them when you need them.

[Seasid]

I asked shooter.

[MateoBeach]

The drug companies and the clinical institutions they sponsor and pay to run phase 3 trials are very afraid of their drug not having a strong enough effect to produce the statistics that will earn FDA approval. So they use the maximum tolerated doses from their phase 1 trial which is on the edge of toxicity, or over it. It dose not tell anything about minimum effective dose that could work just as well with less toxicity for many or most.Real world usage has now shown us that 80 mg enzalutamide works quite well for many with lower toxicity. Just as 250 mg of abiraterone with a meal containing fat gives the same level of effect as 1000 mg taken on an empty stomach.

In response to TA’s statement I would point out that none of us are that median patient in the clinical trial, so each of us is an experiment. So we should take the information from the clinical trials and then monitor and adjust accordingly. We are navigating a diverse and largely unknown landscape.

I would be content with doing the 80 mg enzalutamide in an attempt to increase PSMA expression for your Pluvicto treatments. Repeat PSMA PET scan between treatments may show whether this is helping with your treatments as an individual. Good luck.

[Rondief in reply to MateoBeach]

Thanks buddy