Immunology- Wherefore art thou - Advanced Prostate...

Advanced Prostate Cancer

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Immunology- Wherefore art thou

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12 Replies

Any ideas on how to undergo Provenge (Immunology) treatment while still hormone sensitive?

Or course the FDA wants castrate resistance, so no insurance support.

I know we are not there yet, but I think soon the treatment goal for we "advanced" guys will be Remission, instead of Attrition.

With that goal in mind (with what we have at present) I am on Zytiga/Prednizone/Lupron (14 months), have had whole pelvic radiation (4 lymph nodes positive with the G68 PET), will have chemo. Immunology is missing from this scenario.

Craig

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efsculpt profile image
efsculpt

Thanks, BBruce, lots of good information.

Craig

Tall_Allen profile image
Tall_Allen

Unfortunately, Provenge did not significantly reduce the biochemical failure rate or the metastatic failure rate when it was tried in men who were recurrent after RP and still hormone sensitive.

clincancerres.aacrjournals....

This may reflect a timing issue for immunotherapy - the prostate cancer may have to genetically change enough so that the immune system no longer recognizes those cells as "self." Perhaps immunotherapies start becoming effective when a greater population of PC cells have undergone genetic breakdown to castration resistance . Compared to other cancers, prostate cancer has so far proved to be especially resistant to immunotherapy.

leo2634 profile image
leo2634 in reply to Tall_Allen

Good morning Tall I just want to tell you I look forward to your comments and links in our ongoing fight. You my friend are a wealth of information and an inspiration to me to keep on fighting. I always told my children knowledge is power. Great to have you in our corner.

Brother in arms Leo.

Tall_Allen profile image
Tall_Allen in reply to leo2634

Thanks, Leo. That's very kind of you to say.

efsculpt profile image
efsculpt in reply to Tall_Allen

Dear Tall Allen:

Thank you for the input. I read the clinical trial but came up with a different conclusion. Provenge branch of trial had 3 months longer before Biochemical Failure, plus 48% of them had extended doubling time. That looks like significant positive results for hormone sensitive guys to me. How they concluded "no significant difference from control group" I can't say. Statistics! ("There are lies, damn lies, and then there are statistics!"- Mark Twain)

Regards,

Craig

Tall_Allen profile image
Tall_Allen in reply to efsculpt

Hi Craig-

It's a common mistake you made - blame those darned statistics! The important part was hidden in parentheses: HR = 0.936, P = 0.737. That means the small (6%) reduction was easily explained by random variations due to sample size. In fact, there is only a one in four chance that the time to BCR are really different. In other words, the Provenge treatment made no difference. It also made no statistically significant difference (P=0.421) in time to distant metastases (another well-established endpoint). By consensus, to reach statistical significance p must be ≤ 0.05

The other part of your comment speaks to something called "surrogate endpoints," which is a controversial topic, especially for PC. The authors used time to BCR as their PRIMARY endpoint, which is a good choice because early BCR after treatment is strongly correlated with survival. Survival is the endpoint we REALLY want to know about. In this regard, PC's main "benefit" - it is a very slow killer - is also the main problem in doing prospective clinical trials - it takes WAY too long to get the answers we are looking for. The authors of this study pose the question - could the change in PSADT (a SECONDARY endpoint in this study) be used as a surrogate endpoint? The answer so far seems to be no - it is too erratic, and while its value under, say, 9 months is prognostic, it is not established that all changes in PSADT, say from 12 months to 15 months, are prognostic for survival.

One of the problems in measuring the impact of Provenge has been the very small effect it usually has on PSA. One man in my support group who used it asked, "how will I know if it worked?" I answered, "Because you'll live longer." You see the problem.

efsculpt profile image
efsculpt in reply to Tall_Allen

Dear Tall Allen:

I had to look up "P" value and "HR" value (again!) but I have some idea of what you are saying. Statistical results of clinical trials are the backbone of PC treatment progress. However, I bailed out of Stanford because their treatments were statistically driven. At that time they were not using Zytiga with ADT on hormone sensitive patients (STAMPEDE/LATITUDE results were just coming out).

On Provenge, I can't say it's God's gift, it happens to be the "only kid on the block" at present. The $93,000 price tag for a treatment cycle (if you are not castrate resistant) removes it from "my block".....and then you only get 4 months?! It takes me that long to put my pants on in the morning.

Regards,

Craig

Tall_Allen profile image
Tall_Allen in reply to efsculpt

The price tags are a big problem, and getting insurance/Medicare to pay for a medicine that hasn't been proven is an even bigger problem. A 4 month improvement is actually a big one, as these things go. These medicines are often tested on men who have tried almost everything, and expected survival in the control group of the Provenge trial was just 21 months. Also, remember that these are medians (statistics again!), so half the men were already very sick and died before the 26 months, while the other half may have survived for a much longer time. In fact, almost a third survived more than 3 years. I agree that we want 10 years extra, but there is nothing on the horizon that promises to deliver that much, unfortunately.

efsculpt profile image
efsculpt in reply to Tall_Allen

Yeah. My new oncologist had to send copies of the Latitude and Stampede results to Medicare to get covered.

We all hope we are on the P<.05 side of the Null Curve.

Right now I'm on an immunology "kick". It's fascinating.

Ciao,

Craig

chillywilly profile image
chillywilly

I know UCSF is starting an immunology trial but I’m not sure about the details.

Try contacting this Dr.

urology.ucsf.edu/people/law...

efsculpt profile image
efsculpt in reply to chillywilly

Thanks, Chillywilly, will email Dr Fong. He's "hot!"

Craig

abmicro profile image
abmicro

Wait until your cancer becomes more stubborn and see if any clinical trials are open for other immune drugs combined with something else. A combined treatment is more effective than a single treatment. Provenge alone doesnt do much.

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