NPfisherman in reply to whatsinaname4 years ago

Absolutely, agree... decreasing tumor burden, circulating cells, etc... earlier in the process makes sense and some MD's are becoming proponents of that stance...Hit it while it is weak makes sense to me....if you can get some radiation first, it may work even better. They are trialing that concept.

NPfisherman in reply to Tall_Allen4 years ago

From your study:

Results: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421).

More:

The primary endpoint, while reasonably selected, was also arbitrary. There are no data to suggest that reaching a PSA concentration of 3.0 ng/mL following a brief course of androgen suppression therapy is or is not predictive of subsequent development of metastases or cancer-related death. At the time this study was designed, relatively little was known about appropriate endpoints in the setting of PSA-only relapse after radical prostatectomy. Regrettably, relatively little progress has been made in this area and the field continues to struggle with the design of studies in this patient population. One area of marked progress is the increased understanding of the prognostic importance of PSA kinetics in general and PSADT specifically. PSADT has been shown to be the single strongest predictor of prostate cancer related mortality in this patient population (21–26).

Again: PSADT has been shown to be the single strongest predictor of prostate cancer related mortality in this patient population (21–26).

There are several issues with using this study. Individuals were given ADT prior to study. I do not believe they were given during study. It was also a small cohort. Please see the conclusion as well:

Conclusions: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy

They defined BF as a PSA>3, and if you look at the Figure 3--the PSADT was clearly superior for Provenge. Now, how would it work with ADT combination. I am unaware of studies that did both and looked at time to castrate resistance. Also, there were individuals who took much longer to get to PSADT in the Provenge group. Consequently, the question remains as to whether there is a subgroup that has a much greater response to Provenge than others. Once again, small cohort to draw conclusion on an arbitrary checkpoint.

To say the fish aren't biting and generalize it to all fisherman would, in a word, be to say all fisherman are equal in talent. This is not true.

When one needs a fish (ie: extend life/ cure) , then one will likely look at a variety of possibilities. Some are fortunate not to need a fish, or already got their fish..... Most of us here are forced to fish like maniacs---we don't get to choose when we fish---finding the fish is the key. We will look at what other fisherman do and if successful, adopt that tactic.

All the best,

Fish

Tall_Allen in reply to NPfisherman4 years ago

You don't seem to understand what those "p"s mean. Any p above 0.05 means that the difference is attributable to chance and is NOT statistically significant. You can't make a silk purse out of a sow's ear. Now this was in 117 men taking Provenge (and 59 controls) - it is possible that a larger study might detect a significant difference, but the difference is likely to be small if any.

I agree that overall survival would be a better endpoint, but for post-prostatectomy patients, it may take 15 years until there is usable data. Actually, biochemical progression-free survival has been accepted as a reasonable endpoint.

You also don't seem to understand the trial design. All men were on iADT, so progression only occurred during the vacation. PSADT was NOT statistically significantly different during the vacation among those taking Provenge.

You lost me in your fish metaphor.

Reply (0)Report

NPfisherman in reply to Tall_Allen4 years ago

Exactly, you don't fish, nor do you need to fish. So, why make a fish comment to begin with in replying to me?? I understand the p< .05 is statistically significant. I did understand they had ADT prior to the trial, and that was my point also---What would happen if Provenge were given while on ADT say, or plus Zytiga or Xtandi ? Will this help delay reaching castrate resistance? No one knows, and so, should someone not attempt to get a fish (ie: extend life/ or cure), by doing this and getting Provenge. As regards the PSADT, there were some that were delayed (statistical significance be damned) using Provenge which means there could be a group that benefits.

If there is clear data that is negative, then list it. Otherwise, the trial you listed did nothing more than cloud the water. It does not help the fishing. If I need a fish, I will use the best knowledge I have regarding fishing, but sometimes, you pull out a lure that has some success, and use it.

I know, you are now, truly lost....

Reply (1)Report

Tall_Allen in reply to NPfisherman4 years ago

What I wrote was: "Sometimes you got to fish when the fish are biting." Perhaps you are not American. In America, it is an aphorism that means that the best time to go after something is when the thing you are going after is available. it was not meant as a personal affront.

It seems that you're saying that even this trial was not early enough, that if ONLY they had gotten the Provenge 3-4 months earlier, before they even started ADT, that it could have been helpful? Really? 3-4 months? I can't disprove that, but there's no reason to suppose that's true.

It is possible there is a subgroup that could benefit, but they remain unidentified so far.

If you choose to ignore statistical significance, you are in no-man's-land. That, and the fact that you disliked the study, should also alert you to your confirmation bias.

Reply (0)Report

NPfisherman in reply to Tall_Allen4 years ago

I am an American, and comprehend English. Here was my point (see where the following is in my last post: (and that was my point also---)

What would happen if Provenge were given while on ADT say, or plus Zytiga or Xtandi ? Will this help delay reaching castrate resistance? No one knows, and so, should someone not attempt to get a fish (ie: extend life/ or cure), by doing this and getting Provenge.

I asked you to do the following:

If there is clear data that is negative, then list it. Otherwise, the trial you listed did nothing more than cloud the water. It does not help the fishing. If I need a fish, I will use the best knowledge I have regarding fishing, but sometimes, you pull out a lure that has some success, and use it.

The metaphor of a fish(extending life/or a cure) is lost on you...or of fishing ( searching/trying to extend your life/get a cure) is lost on you as well....The lure would be Provenge. Do you need a fish, Allen? As I understand, you got your fish--great for you....

This is simple....if you have knowledge of a trial where Gusgold can get Provenge and continue his Xtandi, then great. Please provide it. If you know where he can get assistance on this issue then great. Please provide it.The fact that there is not enough data to prove it will work magnificently is not important to a starving man that needs a fish. He is attempting to find a way to extend his life...The fact that there is no negative data should suffice. After all, it is his hand to play, not ours. We are here to help each other. Should we not respect his request unless there is clear negative data?

Should we all wait for the data, and only do those things that we know are clearly positive, safe, and beneficial? If so, then how does one justify participation in clinical trials? I have participated in 1 clinical trial and looking at others. I would rather be in the game, than wait on the sidelines. When one participates in clinical trials, the knowledge benefits many, and possibly yourself also. Perhaps, Gusgold has the same feeling and would rather fight, than wait...If so, respect his decision/ courage and assist him. I have looked and can't provide help. You have contacts...help him, and if you can help him, then you will have my thanks as well as his....

Fish

Reply (4)Report

whatsinaname in reply to NPfisherman4 years ago

Fantastic reply, Fish. Very well put indeed. Even though I am an Indian [not red, just brown ] I can understand you perfectly. Touche !!!

This has got to be one of the best posts that I have EVER read (and, I frankly admit, I have not read all) on this board, imho.

Thank you very much, Fish.

Reply (1)Report

Tall_Allen in reply to NPfisherman4 years ago

Yes, we should all wait for the data, and only do those things that we know are clearly positive, safe, and beneficial, or join a clinical trial where we are carefully observed. People die in clinical trials, so people (like me) who do them are carefully informed of the risks they are taking to benefit others. And because Phase 3 trials are randomized there is no assurance of getting the treatment.

"Cloud the water" apparently means the results do not conform to your preconceived notions. "The fact that there is no negative data should suffice." - So, for example, because there is no data that disproves that cyanide in small amounts kills cancers, that everyone is well-advised to run out and take it? There are lethal risks (autoimmune cascade) associated with Provenge and the cost is $150,000 for 3 doses, so everyone should look for clear data proving safety and efficacy before taking it. The fact is, we have data that shows: no benefit for men with HSPC - why would anyone risk it? This is moot because there is no way that insurance will pay for it until he is detectably metastatic and castration resistant.

Why on earth would Provenge have any effect on castration resistance? The immune system has no effect on castration resistance that I know of - but perhaps you know of some study that suggests that? You can't just make up biology and pretend that it's true. Certainly, we know that it did not reverse castration resistance in men taking ADT.

I do think that Provenge might be particularly useful when used with chemo or radiation.

Reply (1)Report

NPfisherman in reply to Tall_Allen4 years ago

You compare cyanide to Provenge in prostate cancer? Preconceived notions indeed...That seems like comparing apples and oranges......my point was whether Provenge with ADT and Xtandi might....see the word...delay castration resistance. Did I say reverse? Asked you to provide negative data if you had it...nothing from you... I asked if you had knowledge of where Gus might get Provenge since he has an interest to be treated and there is no negative data. (None that you can provide).Clearly, you have no interest in helping out.

But hey, you got your fish....go look at some data...

Reply (1)Report