Xtandi for PSMA expression: Advice... - Advanced Prostate...

Advanced Prostate Cancer

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Xtandi for PSMA expression

leebeth profile image
30 Replies

Advice, please.

My husband is scheduled for his first Pluvicto treatment on August 16. His oncologist just called, and is starting him on Xtandi (enzalutamide) not because he expects it to have much effect on his rapidly advancing disease, but in hopes it will increase PSMA expression and increase the efficacy of the Pluvicto.

Should he take the full 160 mg dose? Ease in by starting at 80 mg? Take it at night?

Any advice about this and even if it’s a good idea, I am all ears.

Husband just finished Jevtana/carboplatin 8 cycles. Is on Orgovyx. Has daily hyperbaric oxygen treatments for severe radiation cystitis. By the way, after 12 of 40 treatments, he is much improved after 3 months of misery. Gross hematuria, urgency, frequency and pain have all subsided.

30 Replies
Tall_Allen profile image
Tall_Allen

Good idea! Full dose if he can handle it.

leebeth profile image
leebeth in reply to Tall_Allen

Thank you. So far he has handled everything else with ease. So 🙏🏻!

smurtaw profile image
smurtaw

I'd ask his MO.

We could guess at it though.

Upregulation of PSMA Expression by Enzalutamide in Patients with Advanced mCRPC - PMC

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

Since the exam is in about two weeks, he could take 40 mg for 2 days, 80 for 2 days, and then the full 160. His serum levels should be around 66% of steady-state. If he takes the full dose for 2 weeks his serum levels would be 74% of steady-state.

I've taken Xtandi before and I was rather surprised at the lack of side effects. I did 40 mg for a week, then went to 80 for a week, and then 160. I don't know if that ramp had anything to do with it, The reason I ramped up was that I was prescribed Zytiga and took the full dose from day one. After a few weeks, I was very bothered by fatigue and reduced the dose on my MO's advice. Then, without her knowledge, I slowly titrated the dose up and felt fine on it. Then I told her and she stored it in her brain as a data point.

Your husband has a defined target date though. I don't know how long it takes for PSMA expression to be fully modified by Xtandi. A chart such as the serum level chart I am attaching would be nice.

There is some support for night time use. Changing the Timing of Enzalutamide Intake from Morning to before Sleep at Night Overcame Enzalutamide-Induced Dysgeusia - FullText - Case Reports in Oncology 2019, Vol. 12, No. 2 - Karger Publishers

karger.com/Article/FullText...

His MO should be the best bet for those questions.

Xtandi serum level vs time.
leebeth profile image
leebeth in reply to smurtaw

Thank you! My brother was in a trial some years ago and he received both enzalutamide and abiraterone at full dose. He eventually cut back to 3/4 dose, but he really did fine. Of course, the trial ultimately showed that both drugs together had no advantage, but he tolerated it all pretty darn well for a guy in his 70’s at the time. His MO is prescribing it at my suggestion, so dosing is really up to me. This has been most helpful.

Praying we can knock this cancer back for a while.

Benkaymel profile image
Benkaymel in reply to smurtaw

Sounds like a good idea to ramp up. I'm due to start enzalutamide soon so will go with the 40/80/160 ramp-up per week per your suggestion. Thanks

smurtaw profile image
smurtaw in reply to Benkaymel

I would talk to my MO first. I'm not certain that Xtandi would be like Zytiga and some other drugs that are easier to take when they are ramped.

Perhaps a longer ramp time if you are going to use it long-term. Maybe two weeks or so at each lower level?

smurtaw profile image
smurtaw

You're welcome. It was odd that the trial showed no improvement. I expected big things.

Best of luck!

leebeth profile image
leebeth in reply to smurtaw

Many were very hopeful the combo would work! It did create a lot of side effects. He tried but eventually dropped to 3/4 dose on each drug.

EdBar profile image
EdBar

Full dose, take it in the evening, fatigue is one of the main side effects.

Ed

Muffin2019 profile image
Muffin2019

How long were the cycles of jevtana, how far apart and side effects, any steroid use during the cycles?

leebeth profile image
leebeth in reply to Muffin2019

He had 8 cycles, along with carboplatin, three weeks apart. He had daily prednisone 10 mg, and dexamethasone three days following chemo. No side effects at all except for one bout of neutropenic fever after the 4th. I personally think that one fraction of palliative radiation to his shoulder in that time frame had an effect on his bone marrow. The oncologist says no, but I am not convinced that didn’t contribute.

Muffin2019 profile image
Muffin2019 in reply to leebeth

Thank you, I hope everything turns out good, keep posting. If I back to the steroids then back to the weight gain and tampering to get off it, still have some from the last meds.

leebeth profile image
leebeth in reply to Muffin2019

He never really experienced a weight gain, but his abdomen was a bit bloated!

Muffin2019 profile image
Muffin2019 in reply to leebeth

I just dropped 10 pounds on xtandi and a blood thinner that was causing issues.

leebeth profile image
leebeth in reply to Muffin2019

Wow, he can't afford to lose 10 pounds! A blood thinner caused weight loss? That is rare.

Muffin2019 profile image
Muffin2019 in reply to leebeth

Not supposed to but my appetite went south, either the eliquist or xtandi caused nausea. The blood thinner made me feel cold and twice passed blood in the urine then passed 2 blood clots after stopping it. It was originally prescribed for a superficial blood clot in my left leg that my mo thought it caused swelling in my ankle.

leebeth profile image
leebeth in reply to Muffin2019

I have been on Eliquis for years. I WISH it caused weight loss! I think it was the Xtandi. If it was simply a superficial clot, anticoagulation is not really needed, but cancer causes a hypercoag state so be on the lookout!

Stoneartist profile image
Stoneartist

I recently switched from evening to morning - and noticed less SE simply because I was active and focussed on other things. Sleep better as well

Rondief profile image
Rondief

Hi leebeth,Your husband is on the same track that I am currently on. I finished 9 infusions of Cabazitaxel/Jevtana at the end of May.

In early June I started Xtandi at the full dose 4x40 in preparation of beginning Pluvicto in July. After about 3 weeks of Xtandi it was kicking my a$$ with fatigue, loss of appetite (I lost 15 pounds), and a bit of nausea. We stopped the Xtandi on July 7th in hopes of getting my wits about me prior to my first treatment of Pluvicto on July 12th (by the way the Pluvicto treatment was a breeze with constipation as the only side effect).

I restarted the Xtandi on July 18th but at the lower dose of 2x40, so far I feel great. I also started taking with dinner but I don’t know it it will make a difference. I have an appointment with MO tomorrow, 8/1 and we are going to discuss increasing the Xtandi to 3x40 or 4x40. If he can handle the full dose go for it! According to the research synergism between the two seems to have huge benefits.

Feel free to message me anytime. Since I’m about a month ahead of your husband, maybe we both can benefit in comparing notes.

Take care and all the best,

Ron

leebeth profile image
leebeth in reply to Rondief

Thank you SO much. Let's keep in touch!

CAMPSOUPS profile image
CAMPSOUPS in reply to Rondief

Hi Rondief,I'm having a bout of "too lazy to look at your bio". lol.

A question for you and Leebeth.

Are you moving onto Pluvicto after Cabazitaxel/Jevtana (in Leebeths hubby's case Jevtana/carboplatin ) because that was the plan all along or because of progression after the chemo tx?

Thanks.

leebeth profile image
leebeth in reply to CAMPSOUPS

Really both. It was the plan all along. My husband’s PSA is down from 41.3 to 2.7, but his scans don’t show improvement and a few areas of worsening. Does this mean chemo failed? Not really, because his scans were progressing very rapidly prior to chemo. So, it at least slowed it down, and maybe helped a few areas be less dense so that the Pluvicto can work better. (That’s theoretical.) I thought it was interesting that his latest PSMA report did not give specific SUVmax values and I plan to ask about that.

I have a zillion questions already for the nuclear medicine guy but if anyone wants to give me more questions, I am all ears!

CAMPSOUPS profile image
CAMPSOUPS in reply to leebeth

Thanks leebeth that absolutely covered my question and of course things are never black and white as your answer attests to.I wish you two the best!

I trust he had a FDG pet scan along with the PSMA scan.

leebeth profile image
leebeth in reply to CAMPSOUPS

He had a choline scan, and since the PSMA showed much more cancer, his Mayo docs, U of Chicago docs, and his local MO think that is sufficient to demonstrate no discordance, except in the opposite direction. I hope they are right! He is having both the Pylarify and the Ga scans when we get to Mayo on the 15th.

Rondief profile image
Rondief in reply to CAMPSOUPS

Mine was more about timing. I’ve already run the gambit of Casodex, Docetaxel, Zytiga, and Cabazitaxel.

Pluvicto was not available until this past June so it was just the next step in the journey.

Otherwise it may have been Radium 223 (Xofigo) which I am told would have eliminated the use of Pluvicto.

CAMPSOUPS profile image
CAMPSOUPS in reply to Rondief

Thanks. I feel the sequencing or choices of treatment after running the gambit become a little murky. Not sure anymore why one is chosen over the other. Pluvicto seems to be all of a sudden overwhelmingly recommended.

In my mind what happened to chemo (docetaxel or more favorably Jevtana/Cab) being used to resensitize the cancer so that Xtandi could possibly be effective after Zytiga fails ?

I guess the benefits of Pluvicto from the trial approval showed much more benefit?

You don't have to answer I am just letting my pea brain wander.

leebeth profile image
leebeth in reply to CAMPSOUPS

My husband’s MO made it clear to us that at this point he did not expect the enzalutamide to have any effect on his cancer other than increasing PSMA expression to make the Pluvicto as beneficial as possible. Maybe that is simply based on how very aggressive my husband’s cancer is, and the fact that abiraterone had no benefit. From the day he was diagnosed, they have talked about Lu-177 for him.

CAMPSOUPS profile image
CAMPSOUPS in reply to leebeth

Thanks and before I get further lost in the weeds of discussion I have meant to say I am sorry to hear of the low response he has had from treatment.

So far I've responded to treatments. No outlier long time milestones. Neuvo dx 1621 PSA and fully metastasized initial Dox chemo and Lupron/Eligard kept PSA around 8 for about 11 months. Started Zytiga and it is failing now after about 13 months. Will do the prednisone to dexamethasone switch and I am getting ahead of myself thinking of when the benefit of dexamethasone wears off.

leebeth profile image
leebeth in reply to CAMPSOUPS

I hope you get some mileage out of the switch to dexamethasone! My husband did not respond to that at all. I think we all “get ahead of ourselves” and think of what the next steps are, as we want to be prepared!

Rondief profile image
Rondief in reply to CAMPSOUPS

It’s also about Pluvicto’s availability. Until June 2022, it was not a tool in the toolbox, unless you went to Europe where it’s been available for 10 years and shown great success.

For me it just happens to come at the end of my journey but for many it may come earlier. Time will tell, long after I’m gone, where it fits the best based in the toolbox of treatments.

Take care,

Ron

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