All the New Drugs: Take sooner (CSPC) or wait for CRPC

I'm new, but hope to be here a while. I put up a long post under the Title "Greetings from a New Member". I realize it would be better to have a descriptive Title, If there's a way to rename your thread I don't know it, So in order to have the Thread in one place I'll copy the post and two responses here.

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From me (anb)

Age 64. Diagnosed Stage 4 bone metastatic end of 2016. Femur, ribs, scapula. Started ADT beginning of February. PSA 240, now (July) 2.75.

Started Docetaxel beginning May. Had four treatments so far.

I'm in a Clinical Trial at NIH where I will receive Prostvac after the Docetaxel treatment is done.

I've done a enormous amount of reading. I see this decade has been explosive in this field (Provenge, Abiraterone, Enzalutamide, Ipilimumab, Nivolumab, Xofigo). One major problem I gather is that they haven't had time to figure out who gets what drug in what sequence and at what stage of the disease. Just this past month there was a blockbuster announcement at the Annual Urological Conference that Abiraterone showed significant efficacy when given along with ADT during to CSPC.
https://www.urotoday.com/conference-highlights/asco-2017/asco-2017-press-releases/96169-asco-abiraterone-slows-advanced-prostate-cancer-helps-patients-live-longer.html

I want to take an active role in my treatment. One big problem I have is that all these new drugs were approved based on studies involving castrate resistant CRPC. Therefore, aside from reimbursement issues, which are significant, it is not standard medical practice to prescribe any of these drugs while still CSPC. It seems possible that some of these drugs would be better if used earlier. That's what happened with Docetaxel eleven years after it was introduced and it's what just happened with Abiraterone. On the other hand, It's also possible that using these drugs sooner in the disease phase may cause them to poop out and you'd have been better off waiting. At this point it's guesswork, though the trend seems to be to use them sooner and as part of a multi-modal strategy.

The problem is that Dr's don't deal in guesswork. My view is that I don't want to wait around for the inevitable castrate resistant phase to get any of these drugs. I understand the medical community doesn't know the right answer, but I'd rather take a chance with an oncologist's best guess than do nothing. It's been hard to bring Dr's around to this view, but I'm making progress. I say to the Dr: -- give me your best guess, tell me all the things you don't know and all the risks you can think of. At that point, in my view, it ought to be my decision. Isn't that what informed consent is all about? The Dr's agreed in principle, though extracting information from them is not easy.

I have a little time to plan, since I can't have any additional treatment while I'm in the NIH Docetaxel/Prostvac Clinical Trial, which will end for me early January. So I'm working hard to come up with a plan.


I have a number of preliminary thoughts on how I might proceed. I'll give more details in due course, though I AM VERY INTERESTED IN THE REAL WORLD SIDE EFFECTS of Abiraterone and Xofigo in particular. And VERY interested if anyone has any experience with the Mayo Clinic Individualized Medicine Center.

anb
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halbert
Veteran Member

Click to send halbert email.Personal Homepage Not Available
Date Joined Dec 2014
Total Posts : 2818
Posted Today 3:05 PM (GMT -6) Quote This PostIgnore Posts From halbert.alert An Admin about This Post.
Anb, thanks for joining our club. It sounds like you're making good moves on your behalf. What I hear you asking is about how clinical trials are structured, and why. The short answer to your question, is that clinical trials are designed as they are to limit the 'noise' in the data. The reason we can't get 'off normal' drugs without being in the trial...is that the trial is trying to show that it works. It's circular reasoning, but that's it.

Maybe someone more knowledgeable will be along to give you a better answer.

In the mean time, welcome, and good for you for getting into the Prostvac trial. We're all watching to see how that one comes out.Age at Diagnosis: 56
RALP on 2/17/15, BJC St. Louis, Dr. Figenshau
58.5g, G3+4, 20%, 4 quadrants involved
PSA 3/10/15: 0.10
5/18/15: <.04
8/24/15: <.04
11/30/15: <.04
2/29/16: <0.04
8/30/16: <0.04
2/15/17: <0.006
My Story: www.healingwell.com/community/default.aspx?f=35&m=3300024
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GaryLK
New Member

Date Joined Sep 2015

The other reason doctors like to wait is that they want to keep "more bullets in the chamber". That is, they want to have more therapies to offer over time.

As my oncologist said to me the first time I met him. We will do Therapies A, then B, then C, then D, then E, and hopefully by that time they will have a F, G, and H available if any or all of the above don't work the way we'd like.

As they is no cure for advanced recurrent prostate cancer, that makes a lot of sense to me. Especially when you have a fast doubling cancer strain, as is my case.

Thus, I wouldn't take abiraterone any sooner than at a point where you know it works. Keep your "bullets" in reserve so as to always have ammunition ready to fight your cancerous enemy.Prostate cancer, RP, Gleason 4+4 = 8 (per pathology), diagnosed as recurrent (advanced) stage T4 (in liver), Average doubling time = 48 days, undergoing hormone therapy, 1st chemo scheduled to start in 3-5 weeks, Zytiga to follow, current PSA = 28.6
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anb Response
Posted Today 4:14 PM (GMT -6)

Thanks guys.

To Halbert: I know that's how Clinical Trials work and it makes sense -- they need to eliminate variables. I'm OK with that -- heck, I'm going to get Prostvac.

To GaryLK: I agree. There are two ways of looking at it. I call the waiting strategy "don't show your hand", meaning don't give the cancer a chance to mute out of it. The do it now strategy is "hit it hard when it's down, preferably from multiple directions". No one know the answer and it probably is different or different drugs.

I'm looking at history. Prior to 2004 all they had was ADT. In 2004 Docetaxel came online. For 11 years they would do ADT and when it pooped out the would move to Docetaxel. In 2015 they concluded, based on trials, that it is better to give them together. And just last month they found Abiraterone so effective it might be used first line instead of chemo.

I'm going with the hit it hard from different directions strategy, particularly if it's your first therapy.

anb-

Here are therapy options for metastatic guys who are hormone sensitive:
/pcnrv.blogspot.com/2017/06/newly-diagnosed-metastatic-m1-but-still.html

I think that Prostvac+docetaxel trial you're on is terrific. The docetaxel increases the presentation of antigens to the activated immune system, and the Prostvac counteracts the immune suppression that the docetaxel might otherwise cause - a synergistic combo. At least, in theory.

Don't worry about the therapies "pooping out." That's exactly what the recent clinical trials proved - that overall survival was better when docetaxel and abiraterone were started earlier. I expect Zytiga will be FDA approved soon for early use, but it may be some time before all the other drugs are. And unless you are very wealthy, your choices are to wait for FDA approval or to get them on a clinical trial.

Based on what we've learned so far with docetaxel and abiraterone, it is a bad idea to wait to use a therapy (see the section "What happens if they are used later?"). It may be that some therapies are only effective if used at a certain point in progression. Provenge, for example, has shown no benefit when used earlier. Docetaxel only showed a benefit when used after there were already multiple metastases. On the other hand, some (perhaps apalutamide or darolulatide) may forestall castration resistance, while others may resensitize castration-resistant PC. Only clinical trials can tell us.

My advice is to listen to everything TA says.

The dude knows his stuff.

Andrew

To Larry E: thanks for the tip on the Kwon video re order of treatment. https://www.youtube.com/watch?v=NkqizmvqJPo
It's 1/2 hour, so I'll get to that
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To Fairwind who said "This is America ! If you have enough money, you can ask for and receive any of these drugs anytime you want...Run your own clinical trial."

That's exactly what I want to do. One frustration is that Dr's don't think that way. They're reluctant to deviate from "Best Medical Practice", which is driven by Phase 3 trials. I don't have time for that.

I knew you had to be your own advocate, but I'm surprised how much I needed to learn on my own so I could ask specific questions about specific drugs that are approved for CRPC but not yet) for CSPC and then push to get the Dr's. to take this exercise seriously
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To Tall Allen: Great Info. InTheShop was clearly right when he said you know your stuff.
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TO ALL: Here's some more specific information about my situation. Biopsy: Cancer virtually everywhere in prostate. Gleason = 8. PSA beginning of this year: 240. Degarelix a few months, now Lupron. As of end of June PSA 2.75 and dropping. Chemo began May 2.

I have 5 bone metastases. That puts me just across the definitional line for "high volume". So, you could say, I'm Low-High Volume.

Here's my current thoughts on treatment plan, a work in progress. I subscribe to the theory that the cancer has been shocked by the Docetaxel and you should kick it hard while it's down from multiple pathways (aka multimodal). There's a risk that I might do better holding some in reserve but I'm not going in that direction. There is a limit to how much I want to put my body through. For example, I'm not looking at Jetvana and likely not Nivolumab or Ipilimumab.

The oncologist running the Prostvac trial I'm in suggested that afterwards I get Provenge as well. I will do that.

I want radiation-- either SBRT to the bone metastases or Xofigo. Xofigo benefit is that it attacks all bone Metastases, not just the ones that can be imaged. I don't know if it's as effective as SBRT. In addition to the obvious anti-cancer effects, radiation and immunotherapy work synergistically. I'm very interested in real world side effects of those treatments. As for SBRT they're generally only doing it if you have no more than 3 metatases. But who came up with that number?

I'm on the fence about ABIRATERONE. I don't know the long term effects of the prednisone they give you with it. I don't know the side effects and I will be living with them for the rest of my life. Also, I will be doing other treatments of limited duration. I'm thinking maybe do those first so I don't have to to deal with both those side effects and Abiraterone side effects. Maybe layer in Abiraterone after those. On the other hand the recent Abiraterone trial with CSPC moves me toward doing it sooner.

Nivolumab and Ipilimumab: I'm going to hold off on those. I figure there's only so many treatments I can pound my body with and those look like more will be known, hopefully soon, about who they can help. I gather they're working on biomarkers to identify those people who will benefit and they have focused recently on BRCA.

Enzalutamide: From what I've seen, if you take Enzalutamide and Abiraterone sequentially then whichever one you take second doesn't work that well. My oncologist was not keen on Enzalutamide generally, so I'm not planning on taking that now, though I haven't completely ruled out taking it simultaneously with Abiraterone.

I'd like to know more about the MAYO CLINIC INDIVIDUALIZED MEDICINE Center.

Lastly and most controversial: PR via Da Vinci if someone will do it. (One Dr. told me "the train has left the station on that; if anyone suggests doing a PR run away"). I've got an appointment with Dr. Tewari who has done something like 7,000 of them. There's not a lot of clinical stuff on PR in metastatic cases but what little there is (retrospective studies) says better OS. Also, the science makes sense to me: the prostate is the furnace, it is immunologically privileged and a continuing source of new cancer cells, and the cancer has been there the longest so the cells have had more time to mutate. Some have even theorized that new bone metastases are initially an intermediate stage and what's in the prostate is more advanced mutationally speaking.

Now all this sounds great but I plotted it out on a calendar. If I do PR, wait to recover, Abiraterone, wait until my body accepts it, then Xofigo (or vice versa) I'm spending all of 2018 and some of 2019 layering on treatments. I gather once your ADT has kicked in and you're finished with Docetaxel you feel pretty good for a couple of years. Those may be the best years I get. And it's guesswork how much all this will improve my OS.

anb

I'm surprised you mention Xtandi instead of Zytiga given the results of Zytiga in CSPC that just came out. My Dr. wasn't keen on Xtandi but I'll ask again.

Provenge I figure why not. It's only three treatments every two weeks -- you can knock it off in a month and the worst that happens is it doesn't do you any good.

From what I've read about systemic radiopharmaceuticals I liked the alpha emitters because they minimize harm to healthy tissue. I didn't understand your suggestion about Heidelberg. I thought it was Xofigo and that's that -- didn't matter where I got it.

As for the RP I thought it would be better than simply SBRT to the prostate because my understanding is that SBRT to the prostate doesn't kill everything. I was figuring RP followed by SBRT to that soft tissue area followed by (or contemporaneously with) Xofigo. I'm seeing Dr. Tewari end of this month and I understand he spends some time with you so I can ask him his take. I don't even know if he'll do the RP. And if it can't be done with Da Vinci I'm not sure I want it.

Keytruda, wow. I thought that might come in much later. Is there anything on that with CSPC? Has that even been approved for PC? It's one thing to get a Dr. to prescribe a PC medication that's currently only indicated in CRPC; quite another to get them to prescribe something that's not even in their current arsenal.

I'm going to be seeing the Dr. running my Clinical Trial at least 9 more times (2 more chemo and 7 for Prostvac). Last visit he started opening up to my exploring other treatments and said "let's continue this conversation".

CART-T is likely the future. I don't know if that will happen in time for me. They may be starting a Phase 1 trial for PC https://clinicaltrials.gov/ct2/show/NCT03089203 and I think that's about it. I'm guessing later phases will be on CRPC, but I'll be there in due course.

In any case I have some time since I can't do anything until January per the protocol for the Clinical Trial I'm in.

I'm really curious as to why your doc doesn't like Xtandi....

anb said...
Provenge I figure why not. It's only three treatments every two weeks -- you can knock it off in a month and the worst that happens is it doesn't do you any good.

Well, the "why not" is the danger of a runaway fatal immune reaction.

anb said...
From what I've read about systemic radiopharmaceuticals I liked the alpha emitters because they minimize harm to healthy tissue. I didn't understand your suggestion about Heidelberg. I thought it was Xofigo and that's that -- didn't matter where I got it.

I suggest you actually read the article and the links in it. There is a world of radiopharmaceuticals to get educated about. Xofigo is specific only to bone because radium substitutes for calcium. Lu-177-PSMA is now in a clinical trial (for mCRPC) in Houston. Ac-225-PSMA-617 is an alpha emitter testing in Heidelberg.
/pcnrv.blogspot.com/2016/12/ac-225-psma-617-extends-survival-update.html
But, as I said, I-131-MIP-1095 seems to be the most promising so far.

anb said...
As for the RP I thought it would be better than simply SBRT to the prostate because my understanding is that SBRT to the prostate doesn't kill everything.

No, that's not correct. In fact, sbrt with a wide margin, say 5 mm, and simultaneous targeting of the pelvic LNs can kill quite a bit more cancer than RP. It seems to create a stronger abscopal effect than conventional radiation.

anb said...
Keytruda, wow. I thought that might come in much later. Is there anything on that with CSPC? Has that even been approved for PC? It's one thing to get a Dr. to prescribe a PC medication that's currently only indicated in CRPC; quite another to get them to prescribe something that's not even in their current arsenal.

It was just approved for a rare variant that sometimes occurs with PC - look at cspivak's posts. A doctor may prescribe any approved drug off label if the patient is willing to pay for it.

To Tall Allen. On Provenge I though infection risk could be adequately managed with strict cautionary measures on my part. Is Provenge any worse than chemo in infection risk.

Also, just an fyi: in this Study I'm in I'm getting Neulasta because I've had chronic sinus infections the Dr. thought it advisable. I can say that they do bloods every three weeks and my WBC are coming in normal. In the trial the price is right. In the real world it's $6,000 per shot.

As to the other stuff I will read that article you suggested and get a little more educated about radiopharmaceuticals. I had thought Xofigo was it for PC.
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To cspivak: On getting genetic information, that is one of the reasons I want to go to the Mayo individualized medicine. I don't know their deal exactly, but they are a non-profit and I read somewhere that they take you if your case is "interesting". I believe they accept insurance and Medicare.

I asked my ONC about Mayo and he said "wait, your tumor is going to change". I come off the Study in January so I was thinking of going to Mayo in Oct. or Nov. and get their advice on what my "plan" should be once Trial is over.

Good discussion, and as always thanks to Tall Allen and others who share their wealth of knowledge. My husband has two of six cycles of Taxotere to go, and his MO (Morgans) and urologist (Penson) both want him to start Zytiga soon after. Their thinking is that we use what is available now in hopes of "knocking down" the cancer, resulting in a more sustained "remission". RP to debulk the prostate area and some lymph nodes is also under discussion. Here are the latest results on that course of treatment:

http://www.practiceupdate.com/c/55363/1/3/?elsca1=emc_enews_expert-insight&elsca2=email&elsca3=practiceupdate_uro&elsca4=urology&elsca5=newsletter&rid=MjY3MjE2OTYwNTYwS0&lid=10332481

The last studies I've seen are reviewed here:

/pcnrv.blogspot.com/2016/08/is-prostate-specific-radiation-still-of.html

Note well the caution expressed in the final paragraph. It will be some time before we have the results of any of those RCTs. Meanwhile, my feeling is that surgery has a high adverse event profile (especially incontinence), and it is likely the tumor has made it difficult to remove without impacting nearby nerves and other organs. Radiation would probably require multimodal treatment to overcome large radioresistant tumors, which also has adverse effects. I think it should be considered, but it is not an easy decision.

The ADT will shrink your prostate and should improve your peeing. You are right that RP will cure your prostatitis. Sometimes cancer growth in the prostate requires a TURP, but not usually. Usually, the shrinkage from ADT is enough. Radiation will shrink the prostate too (Mine went from 55cc to about 25cc) but it takes longer, and there will be acute inflammation immediately afterwards. At any rate, you have time to figure this out after you see how the ADT+chemo affects its size and your peeing.