PSA Rising While on Lupron and Zytiga

[jfoesq]

DX 7 yrs ago at age 54 with several bone mets, PSA in 40s and Gleason 9. Went on Lupron and Zytiga INTERMITTENTLY for 5 yrs with 3 "vacations". (also, had prostate removed along with >30 lymph nodes). After last vacation, my doc allowed the PSA to rise to 5.2 and 1-2 mets showed slight increase and a met in lymph node may have developed, (I wish "we" hadn't let the PSA go up so much before ending my vacation). I re-started Lupron. My old doc stopped seeing patients and my new doc took me off the Zytiga. I continued to respond to Lupron (without Zytiga) for 2+ years, with PSA dropping over time to <.05., until: Oct/19 PSA .08 Then, 2 weeks later in Oct.19 , PSA rose to .12.

Zytiga added to Lupron results: PSA went to .08, .08, .10. and back up to .12. in 2 week intervals. I assume PSA will be .16 or higher when tested again next week.

So- it appears as though the PSA will continue to rise with both the Lupron and Zytiga. Doc wants to continue with the same treatment and scan me in 6 months.( I think scan should be sooner.) Wondering what next step(s) should be and when. If scans show changes, do I take Docetaxel? OR something else. I appreciate your responses.

[Tall_Allen]

This may be helpful:

pcnrv.blogspot.com/2019/12/...

[jfoesq in reply to Tall_Allen]

Thank you for your response, Allen

[tango65]

Your PSA is still at a low value. I could consider to request to measure PSA every month and determine what the trend is and how fast the PSA is increasing. You could also request treatment with Provenge since your PSA is going up even when testosterone is a castration levels.

You could change prednisone for dexamethasone which could make zytiga to work again for a while There are clinical trials to resensitize the cancer to Zytiga using modified niclosamide:

clinicaltrials.gov/ct2/resu...

health.ucdavis.edu/synthesi...

[Faith1111 in reply to tango65]

I have a question, why do you suggest Provenge when PSA continues to rise and testosterone is at castration level? Is that a good time to start it? And why?

[tango65 in reply to Faith1111]

Since his PSA is going up having castration levels of testosterone, his cancer could be considered castration resistant.

Provenge is approved for the treatment of patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). It is usually used when the disease is more advanced than his cancer and other therapies have failed.

I have read that there are MOs using Provenge earlier in the disease process in order to have the immune system already prime against the cancer with the hope it could make Provenge more effective. We should remember that Provenge has been proven to prolong overall survival.

There are not hard data showing that this is more beneficial than using Provenge later. IMHO, I believe that is better to have the immune system primed to fight the cancer as soon as possible. Unfortunately, Provenge is not approved for castration sensitive cancer.

This is a retrospective study done in mCRPC patients treated only with ADT:

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

[Faith1111 in reply to tango65]

Thank you so much for your prompt reply. My brother is going to Dana-Farber tomorrow and this is one of the questions we will be asking his Dr. I believe he fits that criteria right now with no symptoms, zero testosterone and PSA rising on Zytiga. He may be coming off Zytiga and considering what to do next. Thank you so much for sending over the study

[tango65 in reply to Faith1111]

You are welcome. Dana Farber is a good place. I consulted a couple of times there in 2004 and 2006 and they help me to get into the clinical trial for the vaccine Prostvac which stopped the progression of my castration sensitive cancer for 7 years. Prostvac does not work in castration resistant cancer. My son trained as MO and hematologists at the Dana Farber and worked there for many years doing basic research .

I wish you the best of luck on this journey, a fellow traveler,

Tango.

[MarkBC in reply to tango65]

I'm curious about your comment that Prostvac was effective against your castrate sensitive cancer. Mine is still castrate sensitive after 19 months on ADT and chemo at the beginning. I haven't heard about Prostvac.

[tango65 in reply to MarkBC]

Prostvac is an experimental vaccine. There are some data in phase II trials (I was part of one of them) showing a positive effect in hormone or castration sensitive cancer.

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

A phase 3 randomized control trial in mCRPC did not show any advantage.

The vaccine is still used in some clinical trials:

clinicaltrials.gov/ct2/resu...

Perhaps, you could qualify if you are interested.

The vaccine did work for me. I had a PSADT of 2 months in 2006. I entered the study in January 2007 with a PSA of 0.5. I received several vaccinations for 2 years. My PSA initially increased to 0.6. By the 3-4 month it went back to 0.4 and then to 0.3. It remained between 0.3 and 0.4 for 7 years. The lowest it got was 0.2. My testosterone was normal all the time. There is a lot of science in the genesis and production of this vaccine. It is very disappointing that it did not work in the phase III randomized trial in CRPC.

[Kevinski65 in reply to tango65]

Did u get this at NIH? If so didn't they make u take Xtandi as well?

[tango65 in reply to Kevinski65]

I got it at BIDMC (Boston) in 2007 and at NIH (Bethesda) in 2016. No, they did not require Xtandi.

The cancer was hormone sensitive and not metastatic by conventional scans. It was a BCR after prostatectomy and salvage IMRT to the prostate fossa and the whole pelvis.

From 2007 to 2009 I received the vaccine for the first time. PSA went down a little (0.5 to 0.3) and remained stable until 2014 (testosterone was normal). I received a booster (5 doses) of the vaccine in 2016 at NIH when the PSA got to 2, but it did not work.

[Kevinski65 in reply to tango65]

I see, I thought it was pulled completely but I stand corrected.

[George71 in reply to tango65]

is Prostvac available for non met. castrate sensitive PC? -- just rising PSA not on ADT?

[tango65 in reply to George71]

It is only available in clinical trials. You need to check the trials and see if you could qualify:

clinicaltrials.gov/ct2/resu...

Perhaps, this one could be a possibility:

clinicaltrials.gov/ct2/show...

Best of luck!!

[George71 in reply to tango65]

Thanks Tango

[tango65 in reply to George71]

You are welcome.

Best of luck!!

[jfoesq in reply to tango65]

Thx, Tango

[tango65 in reply to jfoesq]

You are welcome.

Best of luck.!!!

[Grumpyswife in reply to tango65]

Hi Tango 65, I am having difficulty convincing my husband's MO to try dexamethasone as a replacement for prednisone as Zytiga is no longer lowering his PSA.

I have printed some of the articles but do you have any recommendations for anything more substantial I can do to convince him to let us try it? His PA told me today that the doc (who is the smartest person she knows) only follows the NCI guideline for proven treatments.

Thanks.

Mary

[tango65 in reply to Grumpyswife]

I am not aware of RCT about the advantages of changing from prednisone to dexamethasone. This is one of the articles:

nature.com/articles/s41416-...

There is not medical reason to refuse to make the change. Prednisone is given with abiraterone to decrease the production of ACTH and avoid the increase in aldosterone which can cause sodium retention, edema, hypertension and hypokalemia.

One can obtain the same result using dexamethasone instead of prednisone. Some MO are not using prednisone at all. They are using eplenerone (an aldosterone receptor blocker) instead of prednisone, particularly in type II diabetic patients. Sometimes is not smart to follow NCI guidelines blinded without taking in consideration the pathophysiology of the medical problem and anecdotal information.

[kapakahi in reply to tango65]

And there's always the downside of "guidelines" - they're for everybody, based on statistics. Well, an individual is not everybody; an individual is unique, and while guidelines may work for some people or even most people, they will not work for everyone. Any good doctor should know this. Of course, that doctor would have to take of the blinders.

[tango65 in reply to kapakahi]

I agree.

Best of luck!!

[tom67inMA]

Before you give up, Google "abiraterone bounce" and see if it may apply to you. PSA can increase at the start of treatment before dropping, and that's generally associated with better outcomes than simply dropping right away.

[jfoesq in reply to tom67inMA]

Thx. I will check it out.

[jfoesq in reply to tom67inMA]

Just checked it out. I will keep my fingers crossed that I am just having a beneficial bounce.

[Grumpyswife]

You may want to consider Xtandi as well even though there is only a small chance it will work after Zytiga fails. However, My husband eventually failed on Xtandi but then got 5 months from Zytiga/Prednisone.

[jfoesq in reply to Grumpyswife]

Thx. Was he on Zytiga before the Xtandi too?

[Grumpyswife in reply to jfoesq]

No. He had Provenge while he was on ADT and Casodex. Then went to Xtandi for 18 months or so until it failed. Then he started Zytiga with Prednisone and surprisingly got another 5 months--until now. Now he is considering chemo but is elderly and hobbled by the previous treatments.

[jfoesq in reply to Grumpyswife]

Thank you for the information. And I wish you and him the best

[Mrsram]

Hello my father was diagnosed with cancer a year ago and has been receiving the hormone injection every 3 months. His doctor checks his PSA levels every 3 months before giving him injection to ensure that his PSA levels are staying low. So far he’s doing great and now doctor has him on ERLEADA. Doctor is planning on using this drug along with hormone injection . Hope everything works out for u best of luck

[jfoesq in reply to Mrsram]

Thx. Same to you and your dad.

[Hidden]

These PSA values are very low for metastatic prostate cancer. Small changes from .12 to .16 for example really should be ignored. They are insigificant noise. Just remember: Measurable is not always meaningful.

Beyond the PSA rise, you really need to see a change in imaging to determine progression. It will be difficult to see anything at those PSAs. My doctor told me it's very unlikely to have progression at those kind of low values. He also told me he has had patients that have been on Zytiga for several years with PSAs fluctuating around 1-2.

I would stay the course for now. I don't see any indication you need to change treatments. If your PSA does start rising consistently to something over 2, you can also switch steroids to Dexamethasone (SWITCH trial). That could buy you some more time.

[jfoesq in reply to Hidden]

Thx

[Escudilla]

7 years. I hope I'm doing as well at years.

[jfoesq in reply to Escudilla]

I hope you are too.

[Rod98168]

Hi jfoesg, I've been on zytiga 250 mg with low-fat breakfast and 50 mg of eplerenone for two and a half months after my last intermittent vacation and my PSA has dropped twice as fast as it did when I was on lupron and 250mg with a low fat breakfast plus 5 mg of prednisone. My PSA was at 4.2 when I started my intermittent therapy again. I started this therapy after reading a study that said you can use the much lower dosage of zytiga and and another study that added eplerenone to eliminate the prednisone to control the mineralocorticoids, because prednisone weakens your immune system and your bones. I'm very happy that I did this as my PSA went down from 4.2 to 0.026 in 8 weeks, which is twice as fast as it ever did on the standard protocol therapy. I rarely have hot flashes and my ankles and calves no longer swell up. And the eplerenone is a potassium sparing diuretic which helps to keep my blood pressure low. My Urology oncologist is aware of my new protocol therapy and is still in disbelief that it actually works better than the standard FDA-approved protocol therapy. I would encourage you to check out the low zytiga therapy study and the use of eplerenone instead of prednisone study. I tried to add those links to this info I'm giving you but for some reason the link isn't coming up but both studies can be found at, ncbi.nlm.nih.gov. I hope this info helps you.

[jfoesq in reply to Rod98168]

Thank you, Rod.

I will definitely look this up and discuss with my MO.

Best to you.

[Concernedwife24 in reply to Rod98168]

We need this study too. My husband is just going to start lupron zytiga and prednisone.

[Rod98168]

I also do a periodic fast which may also be contributing to my PSA dropping faster than usual. I fasted for 4 days the last time which was a month ago and plan to fast again next week. IA study by the USC Norris Cancer institute website says that fasting for at least 2 days helps to boost your immune system and causes the chemotherapy to be more effective in killing cancer cells. It also has the added benefit of preventing illness while on the chemo therapy because fasting protects your healthy cells and weakens the cancer cells in your body.

[jfoesq in reply to Rod98168]

And, again.

More thx.

[jfoesq in reply to Rod98168]

Rod- I was able to find the info regarding the use of Eplerenone with Zytiga,. It appears as though the Eplerenone is used when people have troubling side-effects from the Zytiga and/or Prednisone, but I didn't see anything suggesting its use when the normal course of Zytiga with Prdenisone is no longer effective.

Unfortunately, I couldn't find any info about the fasting you mentioned and not sure it would apply to me as I am already taking the Zytiga.

[Rod98168 in reply to jfoesq]

Here's another link about the low dose 250 mg by Ziga versus high dose. Also regarding fasting for cancer, it works for all cancers and the link for that at the Norris Cancer institute, is cancer.keckmedicine.org/fas...

[Rod98168 in reply to jfoesq]

I forgot to include the link for the zytiga study of low dose vs high-dose results. It is, cancer.gov/news-events/canc...

[jfoesq in reply to Rod98168]

Thx again, Rod. I read it all- interesting info. I will read the fasting article again. As for the Zytiga- it doesn't seem to make a difference whether one takes high or low dose and low dose needs more study.

[Maxoscarlady]

You could try immune therapy with provenge stay on Zytiga when you do this some have had good results from this