Intro and Immunotherapy question

Hi Everyone,

This is my first post but have been following the group for a year which has been very helpful.

Brief history-Diagnosed 5/2015. T4, Gleason 9 PSA never over 4.2, Adenocarcinoma with "Signet Ring Cell" structure. 6 lymph nodes and spot on scapula. Lupron & Taxitare (6 rounds) immediately, PSA .06 and scapula not showing. 2-4/2017 HDR and exterior beam radiation. 10/2017 PSA .265 & mets on 2 ribs and scapula now visible again.

My onc recommends immunotherapy before Zynga/Xtandi. Any comments from those who have had Provenge would be appreciated. A trial is available which adds Yervoy (Ipilimumab) after the Provenge. If anyone has experience with this I would love to hear about it.

The Signet Ring Cell type I have is rare and considered very aggressive. If there is someone out there with the same type please let me know your experience.

I hope this isn't too much to ask at once.


32 Replies

  • The side effects of Provenge are limited. It's not possible to prove it works in an individual, but I believe I got benefit. The Yervoy is promising. If you qualify for the trial, you could help yourself and many others.

  • Thank you Yost for your comments. It is hard committing to a therapy that, on the Yervoy side could have some severe side affects when there is no proof it will help. After the Provenge, do you think your benefit was from slowed cancer growth? I’m told only 7% actually experience a lowered PSA.

  • Hi Mike,

    In the Fall of 2016 I was offered a Clinical Trial of Provenge immediately followed by Yervoy (Ipilimumab) at UCSF. I did the Provenge independently to start. I think the Provenge "took" with my immune system, because of the way I felt, starting about 36 hours after the reinfusions. My PSA was in the 60-80 range then. It did not drop, but it did not keep going up either. (I've had extensive metastatic disease for almost 4 years, and did not do Provenge until I was almost 3 years into treatments.)

    I subsequently declined getting into the Trial to add the Ipilumumab. At the time, I personally made that decision based on multiple factors. My consulting specialist and my own research did bring up the potential Adverse Events of Ipilimumab, as per earlier clinical trials and clinical experience. Many involved "rescues" involving massive amounts of steroids if various parts of the body were attacked by a runaway immune system, due to the CTLA-4 inhibitor of Ipilimumab "releasing the hounds" of killer T Cells. They were high enough, in my mind, that I instead decided to start consideration of either Zytiga or Xtandi as a next treatment option. Not long after I started Xtandi, the Clinical Trial results of Ipilimumab vs. Placebo in advanced prostate cancer were announced, showing no significant benefit, yet many of the same Adverse Events, including 9 patient deaths on the Ipilimumab arm due to Adverse Effects of the drug.

    Many more details about my individual experience with Provenge are contained in my Reply to this Thread from several months ago. "Your mileage may vary.", of course.

    Taking Provenge earlier, rather than later, and while overall disease burden is low, might possibly have more long term benefits, too. Just a hunch. There will likely never be a clinical trial to "prove it". It is also very expensive, and typically requires Insurance preapproval. The Provenge provider and your doctor's staff typically handle that and all the logistical scheduling details for you ahead of time.


  • Thanks Charles for the links and thoughts, I appreciate your response. It is the UCSF trial I'm considering. I'll proceed with Provenge but not sure about the trial. The UCSF trial and the Yervoy trial are different as the current trial is hoping Provenge will set the stage for the Yervoy to work. In the Yervoy trial the stage 3&4 side affects are pretty alarming. My onc says the 3&4 side affects are around 5-8%. for the current trial, I'll need more explanation.

    Several who have had Provenge have stated they thought it helped but no one has given specific reasons. I'm told only 7% have a lowered PSA so I assume recipients think it slowed cancer progression. I was hoping for a window of no growth before going to Zytiga or Xtandi. It sounds like you didn't have a very gap between Provenge and Xtandi.

    The fact I have "only" 3 bone mets is a plus because, according to my onc in the Yervoy trial those with minimal cancer faired the best. Another reason he is suggesting the trial for me.

    Decisions, decisions..........


  • Hi again, Mike.

    Yeah, I had a whole lot of "mets" from the get-go when my PSA was just over 5,000 at original diagnosis, and still had considerable numbers of "mets" as my PSA was again rising from a nadir of 1.0 after initial ADT with Lupron + Zometa.

    To Recap the second "hill" of my PSA "roller coaster" ride, and some of the events/trends:

    Jan 2016 PSA 5.9

    Apr 2016 CT and NM Bone Scans "Stable" for bone mets and lymph nodes, PSA 24.4

    May 2016 Consulted at OHSU, PSA 30.6

    Jul 2016 First Consultation at UCSF, PSA 43.0

    Aug 2016 NM Bone Scan (Stable), Familial Gene Testing (negative), Ga-68 PSMA PET/MR at UCSF (10 "hot spots", mostly bone mets), PSA 48.4

    Oct 2016 Provenge, unrelated A-Fib incident, blood clot in arm used for leukapheresis, did not feel well at all during most of this month, PSA 99.0

    Nov 2016 Started Xtandi, PSA 94.8

    Feb 2017 PSA 6.2

    May 2017 PSA 3.4

    Aug 2017 PSA 1.5

    Oct 2017 PSA 1.4

    I knew all along that I could go with either Zytiga or Xtandi. I chose the Xtandi, in part because I didn't want to have to take the constant Prednisone that would counteract the other things that Zytiga could do in the body.

    Since starting Xtandi my background fatigue has been growing. A little bit of gynecomastia started (no big deal, personally), and my skin got drier, too.

    Now I have to contemplate what will be my own Plans C, D, E, F someday down the road.

    As you say, Mike, "Decisions. Decisions."

    I also feel very Grateful to have been largely asymptomatic, pain-wise, for the past 4 years, despite all the bone "mets".


  • Thanks Charles for the info, it helps to see the big picture. I can only hope I can have future bone mets for the length of time you have and still function. Can you still travel and do normal activities on Xtandi?

    Is your oncologist at UCSF?

    I read the info you sent on the Yervoy trial and the % and severeness of the SEs is scary. I need to find out what the dosage is on the Provenge/Yervoy trial, it's not listed in the trial info online. With my aggressive type I likely won't have near as much time as most so I tend to think aggressive regarding treatments, but one has to balance that with the quality of life.


  • >hope I can have ... bone mets ... and still function...

    >Can you still travel and do normal activities on Xtandi?

    My initial NM Bone Scan lighted up like a Christmas Tree. Not all the bone mets were symptomatic. Only one bone met area at L4-L5 was causing severe pain which put me in the ER and Hospital at original diagnosis. Lupron (and Zometa) took away the pain within 3 weeks. My huge initial PSA drop on ADT was paralleled by my larger lymph nodes reducing in diameter by about 1/2, and even more than that, in terms of volume. Another NM Bone Scan a year later was lighted up only about 1/2 as much. CT Scans showed comparable findings. I'd note that some prostate cancer bone mets may be the type that cause overgrowth of bones rather than holes in bones, so they can still show up on CT scans, but not necessarily be symptomatic if "damped down" by ADT or other treatments.

    Xtandi during the past year for me has been mostly a continuation of the trend I've felt on Lupron for the past 4 years. More background fatigue, though. Less peak energy. I am age 69 now instead of age 65. I still walk 1-2 miles each day. I still mow my lawns (albeit deliberately slowly, and taking breaks to cool down in hot weather). I drive the car just fine. I drove the 810 mile round trip to the PCRI Conference in Los Angeles in September of this year.

    I have a local "neighborhood" oncologist who sees all kinds of cancer patients about a mile from where I live, with whom I started at first, and where I get routine Lupron, etc. More recently I've consulted at UCSF:

    If you would like, send me a Message with an email contact for you, and we can continue trading any further "details" that way, rather than clogging up this Forum any more than necessary, or dragging out this Posted thread.


  • The 2 year negative study on Yervoy was reported by Tomasz Beer in oregon, well known and respected. I myself would always weigh heavily his conclusions.

    I have had Provenge. I put more weight in the negative side now than the positive side, but some patients like it.

  • Thanks martingugino, the article is quite a read. I’m seeing red flags because I’m told Provenge will not lower PSA so stopping progression would be the benefit but I’m having a hard time finding someone who has had that experience. BBruce said it arrested progression for him but didn’t state how long. Was progression stopped for you and if so how long, if you don’t mind me asking. It sounds as if you might not have taken Provenge knowing what you know now . True, or am I miss reading your comments?

    The Yervoy trial I read , used by itself looks pretty bad. The UCSF trail I’m considering uses Provenge to identify the PC cells followed by Yervoy to release immune cells to attack them. Independently these two drugs may not do well but together might be beneficial. I’m still on the fence as the side affects from the Yervoy trial were a little scary. The Yervoy dosage etc. I need to ask about. Thanks again,


  • I did Provenge because 1) it was FDA approved at the time, 2) my doctor was in a wait and see mode (wait for WHAT?) 3) and I hoped it might be that Provenge fought circulating tumor cells, and that was why one did not see a PSA decline, but got a survival advantage.

    Now with the idea that (apparently) only a few of the circulating tumor cells are "stem" cells (is this even true??) , that logic seems less important.

    I might possibly still do the Provenge, based on Chuck Drake's dismissal of the criticism, but I would definitely make a serious effort to find out what he has to say about this alternate view of the trial results. [I would look more carefully than I have at the data in the article. I have not because the decision is behind me, I suppose, and other things are more relevant for me.]

    The idea of the trial (you say) is that the dendrites (ie Provenge) see the prostate cancer, (because they see the PAP on the cell membrane) and the Yervoy disables the shields that the cancer cells try to put up. This sounds a little like fantasy, since the dendrites are antigen presenting cells, that have to rouse T-Cells first to become allergic to PAP, of which there is a lot of in the blood. ie: there is a blood test to measure PAP levels. Maybe these speculated T-cells ignore "free floating" PAP, and only see membrane bound PAP?

    The KHAN academy has great videos on the immune system: dendrites, b-cells, antibodies, T-cells....


  • That is good advice Martin, scientifically over my so I need to get up to speed. Thx for the link.

  • Well basically, Provenge is classified as a vaccine, similar to the flu vaccine. The difference is that with flu, the point is to present the body with a weak version of a future external danger, that the immune system can attack. With cancer, the vaccine has to be something (a protein) that isn't too harmful to the patient if it is attacked by the immune system, but that is something (or very like something) that the cancer cells need to survive.

    Luckily, we don't need the prostate. So that provides some leeway.

    With Provenge the target is (membrane-bound?) PAP (aka PSAP).

  • A few short videos from PCRI on Provenge

    Dr Chuck Drake:

    Dr Eugene Kwon

  • Yervoy is approved for other things, so the safety should be reasonable. Check of course, and Kwon likes it. (Of course, he worked on the intial trials of it.)

  • I once read a case report of a man given Lupron + Provenge. After a while the Lupron was stopped and the guy went several years with no climb in PSA. I think the theory advanced here was that Provenge can't handle an aggressive cancer but if the cancer is seriously weakened by ADT, the immune system can tackle the weakened tumor cells.

    I realize that a report of a single case is useless for drawing conclusions, but it raises questions about when is the best time to take Provenge. It sounds plausible that getting ADT and Provenge together would work better than getting them separately. We've seen now that that is true with ADT + chemo. It's something to discuss with the oncologist.


  • Interesting information Alan. I have just become CR after being on Lupron 18 months. My onc wants me to start the Provenge soon as he says it works best before the cancer gains strength.

    I think you are suggesting Lupron and Provenge before becoming CR, if so that horse left the barn, unfortunately. I’ll ask my onc if that was an option in his mind. I’m still on the fence regarding the Provenge followed by Yervoy trial.


  • Actually, I don't think that Provenge is FDA approved to take before CR. Other than that, the word is take it earlier rather than later, and don't let it impede any other treatment that you are considering, or is warranted.

  • I have taken them. Zytiga & Xtandi may work for couple of years , and they will lower your PSA by higher than %70-%80, provided you are on the right diet, Provenge will not. Having couple of more years of quality life is very nice.

    Unfortunately, these drugs will start mutation of TP53 , L702H and H875Y genes . Specifically after TP53 ( genome guardian) mutation , the PC becomes more aggressive and metastatic.

    I can’t trace back which genes of mine mutated due to Provenge. Provenge did stabilized my PC and stopped it’s progression.

  • Thank you Bruce, several have commented Provenge helped but didn't explain in what manor. I guess even though it does not lower PSA, in your case it stabilized it stopping progression. If this is correct, how long did this last before moving on to Zytiga & Xtandi? Did you use both Zytiga & Xtandi? I have read, since they both operate in a similar fashion once one runs it's course the other will not be affective. Was your experience different?


  • Mike

    I had tree treatment of Provenge, every two weeks . I took Zytiga first , then Xtandi. Xtandi didn’t work in my case. You shouldn’t take them together , one block the effect of the other. In my case Xtandi didn’t work.

    A better Immunotherapy over Provenge , and a lot cheaper Is high-dose vitamin C by intravenous infusion. Here is the link on NIH site.

    Your oncologist may not know, or may act as if he doesn’t how to administer the high-dose vitamin C treatment . You may have to research and collect the required info and present it to your oncologist .

  • Thanks BBruce - wow, something new everyday, I'l look into it.


  • The trial to see what the effect of taking them together is ongoing.

    It may not be approved or standard of care, but it is not accurate to say that you should not take them to gether.

    I assume that cost is the reason that they are not taken together, and that it has not been the subject of a (completed) trial.

  • This is the trial I'm considering.

  • A nice thing is that UCSF has lots of smart people, and if you want to go there in the future, they will already have your records.

  • BBruce: Your link to Vitamin C says

    "While generally approved as a dietary supplement, the U.S. Food and Drug Administration (FDA) has not approved the use of IV high-dose vitamin C as a treatment for cancer or any other medical condition".

  • Hi Martingugino

    Thanks for reply and copying a comment from the link I sent . If you do more research on IV high-dose vitamin C as a treatment , you will see a lot more , for example in this link , from NCBI

    Patient-1 : you will find a patient-1 cancer was almost gone , by using IV high-dose vitamin C. If you continue do research you will find some hospital in US use IV high-dose vitamin C for cancer treatment. These hospital will send you the protocol they use if you fax them your prescription. Please spend more time doing research on the material you post .

    Thanks again.

  • You posted a link, and I posted what that link said.

    What's the problem?

  • Dont stop after provenge, or delay any othertreatment because of it.

  • Provenge does not "last", in the sense that your treatment should not be conceived as a series of sequential failures.

    Ah, I see I already said that.

  • I'm always surprised by these discussions. If you can get Provenge and insurance will cover it, why not? I did it and the side effects were minimal. No, it doesn't reduce PSa and may take months to become effective. But if it can help it's worth a shot.

  • I just finished Provenge treatment so too early to know results. I am stage 4 and been fighting since 2006 after radical surgery. I just joined this site so I will try to let you know future prognosis.

  • WW7070 thanks for the reply, I would appreciate a update as you progress. Good luck, Mike

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