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Advanced Prostate Cancer
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Modified Citrus Pectin ... again.

This post discusses the credibility of modified citrus pectin [MCP] as a concept & as a product for men with mets. Gus Gold prefers to defer to Dr. Myers, who saw no benefit in patients who used it, while Nalakrats cites an Israeli study (no link given).

A year ago, I reviewed the literature in:

"Foods/Supplements-Vitamins: Modified Citrus Pectin"

The first PCa study was published in 1995.

It is estimated that there are three million men in the U.S., living today, that once received a PCa diagnosis. With a product that has been around for over 20 years, I imagine that a large number of men have tried it or are currently using it. But so far, there hasn't been a lot of excitement generated.

As I mentioned in the earlier post, the only human study on PubMed is the 2003 paper (Dr. Strum was involved), where:

"We found that the PSADT increased ... in seven (70%) of 10 men after taking MCP for 12 months compared to before taking MCP."

Two months ago, I posted:

"ASCO Genitourinary Cancers Symposium (PectaSol-C modified citrus pectin)"

This is the study that Nalakrats mentions. It is not on PubMed & I doubt anything has been published yet.

"A stabilization or improvement (increase) of PSA doubling time was noted in 79% (n = 27) of" patients.

This appears to be the trial:

clinicaltrials.gov/ct2/show...

It is supposed to be completed by August.

"Study Director:Isaac Eliaz", who happens to be the MCP inventor.

Both studies are similar. In the more recent, the men had undetectable PSA after primary treatment, followed by biochemical relapse with negative scans.

MCP, the term coined by Eliaz, consists of short-chain nondigestible carbohydrate that can be taken up by the gut & into circulation. It just so happens that Gallectin 3, a protein that may be present on the surface of PCa cells, has an affinity for binding to carbohydrate. Gallectin may also be involved in the process by which circulating PCa cells dock, & also in the ability of distant cells to clump & form colonies.

So the idea is that MCP gums up the works & interferes with metastasis.

Neither study looked at metastasis - only PSA doubling time [PSADT].

Given the duration of the studies & the sustained increase in PSADT, there is presumably a direct effect on local tumors - not just on circulating tumor cells.

But, for men with advanced PCa, the question is whether MCP is able to have any effect on existing bone mets. We aren't likely to see a meaningful trial, IMO, so it requires a leap of faith.

How would we prove a benefit while on ADT, unless CRPC?

Of course, preventing new mets is always beneficial.

An account of the recent findings is below.

-Patrick

businesswire.com/news/home/...

“With more than 60 percent of patients in the trial showing no evidence of disease progression, the results imply improvement over historical cohort data. No patient discontinued therapy because of side effects,” said Daniel Keizman, M.D., lead investigator of the multicenter trial study and head of the Genitourinary Oncology Service at Meir Medical Center in Kfar-Saba, Israel.

Of the first 34 patients completing six months of treatment, 27 (79%) showed lengthening of prostate specific antigen (PSA) doubling times, which is a measure of the progression of the disease. These results indicated that P-MCP may be controlling their cancer progression. Twenty-one patients (62%) showed improvement or stabilization of disease, without any progression. In 13 patients (38%), disease progression was seen, with 10 patients (29%) progressing only by PSA and only 3 patients (9%) progressing on bone or CT scans. In addition, P-MCP produced no significant side effects during the study period.

“Following surgery and/or radiation, about 30 percent of prostate cancer patients relapse biochemically with rising PSA levels. The benefit of androgen deprivation therapy, the typical treatment used in this situation, has not been demonstrated and may be offset by significant toxicities,” said Dr. Keizman.

The clinical trial is looking into the effects of P-MCP, which is a form of soluble, dietary fiber. Normal pectin contains long-branched carbohydrate molecules that cannot be absorbed by the gastrointestinal tract. P-MCP is a low molecular weight pectin with shorter fibers, providing greater bioavailability and therapeutic value. In addition, P-MCP has been shown to be active against galectin-3, an inflammatory protein overexpressed in cancer cells and linked to tumorigenesis and metastasis.

In the study, patients with biochemically relapsed prostate cancer, with progressively rising PSA levels in three or more tests, were enrolled in the prospective trial. Participants received 4.8 grams of P-MCP, three times a day, for six months. Since all patients demonstrated progression before the study on consecutive PSA tests, the reduction of PSA doubling time is a promising result.

This research builds on two previous clinical trials showing P-MCP consistently slows PSA level increases. A final analysis of this six-month study is planned for late 2018. Patients who did not progress clinically at six months are being treated for another 12 months. A full report, including 18-month data and correlative analysis, will be released once the data is complete.

“We are happy with the current results suggesting that P-MCP therapy may be active and safe in this setting. We are planning a future phase III randomized trial to assess the clinical benefit of P-MCP treatment in this setting,” says Dr. Keizman.

Source: Effect of PectaSol-C modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in patients (pts) with nonmetastatic, biochemically relapsed prostate cancer (BRPC): Results of the interim analysis of a prospective phase II study.

Daniel Keizman, Moshe A. Frenkel, Todd Michael Edwards, Eli Rosenbaum, David Margel, David Sarid, Victoria Neiman, Maya Gottfried, Natalie Maimon, Ilan Leibovitch, Hadas Dresler, and Isaac Eliaz. Journal of Clinical Oncology 2017 35:15_suppl, e16588-e16588

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An important point was touched on. Since Big Pharma has no interest in any substance or protocol that they cannot patent, there will never be Level I clinical trials of any natural substance. I am 25 years out from my own cancer diagnosis and couldn't take chemo. One of the things I looked at, about 2 years later, after the first of a 9-year series of recurrent tumors, was MCP. I took it from time to time even though there was no evidence it could be effective for breast cancer. But I speculated that prostate and breast were similar in that both were hormonally driven. Anyway no harms shown and here I am. (not necessarily related aspects).

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Pat,

I once ran MCP by an Onco and he said these researchers could make a study come out any way they want. With Eliaz running a study, the same guy selling the product, there is a slight conflict of interest. I got to go with Myers, 20 years on the market and no excitement..if a product gets results there is extreme excitement...the perfect example is PCSPES

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This is an interesting report. If it is accurate, and not a result of a potential conflict of interest that Gus points out, the results are quite good since many of the patients showed, not just a slowing of PSA doubling time but an absolute stopping or even regression of disease progression. Also, if I'm understanding the report, these men did not take any hormone therapy before or during the trial.

One point that surprised me was '"The benefit of androgen deprivation therapy, the typical treatment used in this situation, has not been demonstrated and may be offset by significant toxicities,” said Dr. Keizman.'

Huh? If PSA doubling time is the standard by which MCP is evaluated, Lupron beats it by a mile.

Alan

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The devastating results of early chemo/hormonal therapy l’ve reported elsewhere. Leswell is still alive and a non-trial guinea pig for Vantas plus P-MCP, etc. No monitoring for six months even though requested in writing a month ago. Perhaps the absence of injections is a life extension agent in itself given the treatment-caused lymphedema. Thank you, Patrick. Congratulations AnnieA!

Just noticed the price of Pectasol on Amazon went from $96 to $70, but there is only one in stock. Heading there before it’s sold. The stuff (Les calls it “dirt”) in which we place our faith! Mrs. S

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I saw the ADT statement and went WTF? I have "particularly aggressive" PCa and Elligard / Trelstar have kept me undectable for years. One vacation after 1 year of Elligard showed rapid (< 2 months) doubling time. I literally live because it works. I call B.S. on Dr. Keizman. But I will try p-MCP when I find it.

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" If PSA doubling time is the standard by which MCP is evaluated, Lupron beats it by a mile."

I'm not so sure. ADT (Lupron and others) tends to fail, with a mean time to failure of two years. More than one paper I've read used the term "invariably" to describe the failure of ADT and the emergence of Castration Resistant Prostate Cancer. Once that happens, PSA doubling time becomes very, very short.

Keitzman has a point - several studies show that ADT does not confer significant long-term benefits. Put another way, men who get ADT don't live much longer than men who don't. Men on ADT also report major toxicities and quality of life degradation.

That doesn't contradict the experience of many here who started ADT and saw their PSA drop, or even better mets and tumors shrink. That's great! But there is no way to know what that same man would have experienced if he had chosen a different treatment.

The only way we have to tell is large studies with some men getting ADT and others not. It is those studies that show not much benefit to ADT. Put another way, while PSA may have dropped, the men on ADT might have lived just as long, and almost certainly been happier and healthier, without ADT.

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I see your points here. In the past (i.e., more than 10 years ago), it was widely believed by PCa experts such as Patrick Walsh and many others that ADT relieved symptoms but didn't extend life. In his book _Surviving Prostate Cancer_, (an earlier edition, I haven't seen the later ones), he said he thought that ADT should not be used until a patient experiences symptoms from the cancer. He thought there was no point using up the benefit of symptom relief before one has symptoms, and no point experiencing the ADT side effects until the cancer effects were manifest.

As I understand it, more recent studies have shown that ADT does extend life, especially so if given early. Even when given late with PSA readings in the hundreds and even the thousands, some men in this group seem to have controlled their cancers for years. The more recent ADT drugs - Firmagon, Zytiga, Xtandi - have extended life even further for many men.

Here's an article from Harvard Medical School, originally published in 2007 and reviewed in 2011:

harvardprostateknowledge.or...

Look especially at Table 1, showing significant cancer specific survival benefit at 5 and 10 years for men getting immediate ADT vs. delayed ADT in a randomized clinical trial.

I kind of like Beermaker's idea. Try P-MCP and other supplements that have shown benefit for PCa patients, but start ADT right away, without waiting to see if the supplements help.

Alan

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Those are good facts and arguments, and I appreciate your taking the time to post them.

I'll disagree for 3 reasons. That doesn't mean I'm against ADT in all circumstances, far from it. I've been treated with ADT. My intent is to show that the decision is more complex than the studies and especially the Harvard review article suggest.

The study cited in Table 1 is not only small (98 men) but much more specific than "men who had prostate cancer with lymph node metastases," which is a direct quote from the Harvard review. So my first reason for disagreement:

1) I can't read the full article, it is behind a paywall, but the title shows the error:

Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy

(emphasis added).

So the study was for a very specific group of men, and cannot be extrapolated to all men. If you haven't had RP with pelvic lymph nodes removed, the study is not directly applicable.

It isn't very surprising that this particular group of men would benefit from ADT. Positive nodes are a form of metastasis. It's "locally advanced disease" rather than distant mets, but the cancer has escaped the organ, and there are almost certainly micro-metastases elsewhere in the body. ADT remains the front line therapy for those cases, and this study provides support for that.

This study does not provide support for going on ADT after an RP with clean margins and no lymph node involvement. That is a different stage of the disease, and the authors didn't study that.

The second argument involves the odds of it helping you. There are two parts to this argument: the number needed to treat, and what is being measured.

2) Again, I can't see the full article, but let's make a stab at calculating the number needed to treat (NNT) for each approach.

I won’t go into all the math here, it isn’t hard but this forum doesn’t lend itself to typing equations and formula. (I’d really appreciate some pointers for how to format things like HTML links, image links, and blockquotes. The codes I use in other forums don’t seem to work here.)

I normalized the results for both groups to 47 men – in the actual study it was 47 and 51.

The number needed to treat to keep one additional man alive after 5 years is 5.2. That means 4.2 men got ADT and had no benefit from it, one man did benefit. Put another way, there was a 19% chance that ADT would extend your life at least one year. There is a 81% chance that it won't do any good.

For 10 years, the NTT was 3.6 men, so 2.6 men got no benefit. Now the odds of benefit are 28%. The odds of it doing no good are about 72%.

So taking ADT, like all the other treatment decisions we face, is a bit of a crapshoot. The odds are against you. I’m being unfair to craps here – you can go to any casino, plunk down a bet on the PASS line, and have a 48.6% chance of winning. That’s roughly twice as high as the odds of ADT benefiting this specific group of men.

So the results don’t look quite as strong when you look at them in a different way. Same numbers presented differently, that’s all.

But even more important is what is being measured. The Harvard review’s Table 1 is for Deaths from prostate cancer. That fine, but prostate cancer is a disease of mostly older men, and my goal (and many other men’s goal) is to die WITH prostate cancer but not OF it.

Again, I don’t have the full study, but the abstract shows that the effects of ADT were much stronger when measured in deaths from prostate cancer. The Hazard Ratio is basically the number of of men who died without early ADT divided by the number who died with early ADT.

For men who died of prostate cancer, the hazard ratio after 11.9 years was 4: about 24 deaths in the non-early group divided by 6 deaths in the early group.

But the hazard ratio for overall survival was less than less than half that: 1.84.

Since I don’t have the full data I can’t make the NTT calculation. Given that the hazard ratio is less than half, I would expect the NTT to be about double. So in round numbers, the odds of early ADT keeping one man alive an extra year would be about 10% after 5 years and 15% after 10 years.

Casino operators would go to jail for offering you those kinds of odds – it’s not an honest game. Cancer isn’t entertainment, but there is a lot of chance involved, and it is often useful to calculate your odds.

My third and final point is this: ADT has very bad side effects. I speak from experience, and those side effects are documented in the medical literature. They are often minimized and dismissed in both literature and practitioners’ offices. This is demonstrated in the Harvard review.

An article of 5,700 words devotes exactly 78 words to ADT side effects. There is zero discussion, just a simple list. The message is clear: suck it up. I could say “man up” but of course the essence of ADT is emasculation, un-manning the patient.

The truth is that ALL men experience side effects of ADT. What differs from man to man is the number and severity of those effects, and how willing the patient is to tolerate those effects.

For a man who makes his living driving a truck or working in a factory, slight brain fog or even significant cognitive impairment may be acceptable, especially if he hasn’t calculated the odds. But a man who makes his living with his mind, say doing engineering or research, would probably find those same effects severely distressing or intolerable. Would you want the next bridge you cross to have its design checked by a man whose effective IQ has been cut by 30%?

The loss of libido will similarly be valued differently by different men. There’s no right or wrong to this, it is up to each of us to decide what is important to us and how to best spend the time allotted to us.

The little throwaway last line in the table – “changes in the heart’s electrical signals” is particularly dishonest. The truth is that men who take ADT are much more likely to experience heart attacks and strokes. When they die, their deaths are not attributed to cancer. But they died because of their cancer treatment. That is a big part of the reason that the numbers for overall survival are so much less than the numbers for dying of prostate cancer.

I could go on at length, as the 78-word summary is both incomplete and fundamentally dishonest in not acknowledging the very real role these toxicities should have in an informed treatment decision.

But my point is this: ADT helps SOME men. ADT hurts ALL men, some more than others, some who mind more than others.

In summary, to make an informed decision about any treatment, you need to consider very carefully. All of the treatment options we are currently offered have severe, life-changing effects. All of them have rather poor odds.

If you only look at the good things that happen when you take ADT, or any other treatment, you are likely to conclude that it is a good idea. But the wise patient looks at both the good and the bad things, weighs carefully how much each of those good and bad things mean to HIM and his loved ones, and then makes his choice and takes his chances.

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Well, you've given me some education about all this, which I appreciate, and it reminds me that I need a lot more education to fully understand the statistics. But I will add a few more notes in favor of ADT.

1. ALL of the men in the study, in both arms, had ADT. The difference between the two arms was whether the men had it early or late. It may be the case that men in the same category who had no ADT would have still higher death rates in 5 or 10 years.

2. Death was the only thing reported in this table but there are other issues on the positive side to consider besides the the reduced death rate. What symptoms did the men in the different arms of the study have? How many experienced cancer pain and debility in the five and ten year periods, with what intensity and for how long? The "help" that ADT gives to patients may extend to other areas besides the death rate.

3. There are some men with cancers that are not hormone sensitive at all, but for the majority of men, I suspect that ADT benefits are present. In our statistical reporting we look for hard thresholds. Death is the easiest to measure and years are the easiest measuring points. But I suspect that there is a trajectory with no cancer at one end and pain, debility and death at the other, and for most of us, ADT slows down our passage along that trajectory. If a man dies at 3 years or at 4 years he still goes into the 5 year death category for the purposes of constructing the tables. If he dies at 6 years or at 9 years, he still goes into the 10 year death category. But it's a mistake to think that men measured in the same category all had the same benefit. Perhaps the statistical measures you made account for this (kind of like an reporting an instantaneous acceleration on a curve), but it's worth noting that it's very possible that most of the men, both those who died and those who didn't, lived longer and with less pain and debility than they would have experienced without ADT.

Unfortunately, we still don't know who will benefit most from ADT before actually trying it, or how tolerable the side effects are for a given man. We don't even have a perfect grasp of who should be treated with surgery or radiation much less with ADT.

My own experience with ADT (Lupron) was limited to a little over five months adjuvant to my radiation treatment. I didn't like it at all and was glad to stop taking it. However I was able to ameliorate some of the symptoms by frequent exercise and even managed to enjoy sex - though with less regularity and far more effort than before ADT. I chose to use ADT after reading a report of a trial claiming that 6 months of ADT raised the success rate for radiation (no recurrence in X years - don't remember what the X was) from 5/8 to 7/8. That was almost 15 years ago and I still (knock on wood) have not had a recurrence. Of course I don't know if I'm in the 5/8 group or in the 2/8 group added on to it, though I do know I had Gleason 4+3 and the tumors had already penetrated the capsule wall before my treatment.

The doctors see their first responsibility as preserving life. I know that my wife and children wanted me around and valued that more than preserving my sexual and athletic abilities, and I wanted to live too. There's no way to know if I made the right choice, but I'm not sorry I made the choice that I did.

An interesting discussion.

Alan

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Having defended ADT in my postings, I feel that I should also add that I totally agree with you that alternatives to ADT are highly desirable. ADT has nasty side effects. I'm hoping that further developments in immunotherapy, systemic radiotherapy (e.g., Lu-177), and other things that aren't on our radar screens right now will eventually provide an actual cure for PCa and leave all of us free of the disease.

Alan

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I'm enjoying the discussion, and appreciate your comments.

I'm not sure that ALL men in the study had ADT. It's true that the second arm didn't start ADT until they had symptoms, but I didn't see anything to indicate that all men progressed to symptoms and ADT treatment.

Your point that there are other possible benefits to ADT is a good one. I've never read any study that did what I considered a credible job of even attempting to measure quality of life issues. How much pain meds? Energy? Happiness? Enjoyment of family, friends, food, drink, whatever? There are many aspects to quality of life, and while they are difficult to measure, that is no excuse.

Sadly, most of the studies are similar to the dismissive attitude of the Harvard Med School review you cited. A 78-word list of side effects that is both incomplete an dishonest, accompanied by 5000+ words of detailed discussion about treatment options and benefits.

Like you, I took Lupron for 5 months. I found it intolerable. I also kept up with frequent exercise and managed sex, but the depression, lack of energy, lack of drive, lack of desire for ANYTHING, not just sex, continuous hot flashes, insomnia, and severe cognitive impairment did not respond to the many different things I tried.

My decision was that life on Lupron was not worth living. I'm not so afraid of death that I will spend the rest of my days as a drooling, sad-sack vegetable in exchange for a slim chance of a few more months of existence.

And like you, there is no way to know if I made the right choice, or the best choice, but I am content with my decisions and remain resolute and determined. I don't know if any of the new treatments in the pipeline will come in time, or be effective, but there is no lack of things to learn about and try.

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The link to the ASCO abstract:

ascopubs.org/doi/abs/10.120...

Interesting: the Abstract Discloure found at

coi.asco.org/Report/ViewAbs...

states in part

Isaac Eliaz - No Relationships to Disclose

Eliaz is study director, but that is NOT "running the study." The lead author of the paper is Daniel Keizman. The clinical trial link shows that the study is being done in Israel. Eliaz lives and practices in California.

From the clinical trial description:

"Investigators

Principal Investigator: Daniel Keizman, MD Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center

Study Director: Isaac Eliaz, MD, LAc, MS Amitabha Medical Clinic and Healing Center

Study Chair: Moshe Frenkel, MD Clinical Associate Professor, University of Texas"

The PI has much more opportunity to affect the outcome, especially since this is a single site trial. I don't normally start by assuming that study authors are dishonest, even if they have skin in the game. I like people with skin in the game.

Anything Eliaz proposed when the study was being set up was vetted by Keizman and Frenkel, plus ethics committees, and almost certainly others. While I don't understand Eliaz's denial of any financial interest, that could be because the actual question is narrowly defined. He doesn't benefit directly from the study, although one would expect indirect benefits to Pectasol-C sales if the study shows significant benefits.

The statement by the onco that "these researchers could make a study come out any way they want. " is a sign of cognitive dissonance. It's a non sequitur, the answer does not address the question. The onco can't (or isn't able) to find fault with the study's methods, but he doesn't like the results, so he dismisses them.

Nonsense like that has gotten more than one of my doctors fired. I hire them as technicians with better training and experience than me. If they can't or won't think about the questions and information I bring to them, they are fired! Too many choices to put up with arrogance and ignorance. These are life altering decisions we face, and I need competent assistance.

My primary question about this study is how they measure PSA doubling time (PSADT). The method most urologists and oncologists used is based on a deeply flawed paper. It's so silly and stupid it isn't even wrong. I hope that the authors of this study had someone who understands elementary mathematics and statistics do (or at least check) their PSADT calculations.

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I second FCoffey’s comments. I don’t see an obvious conflict of interest, because MCP is not patented (a particular formulation may get patent, but there will be plenty competing products on the market).

Daniel Keizman is a well published researcher at a reputable institution. Could he commit an outright fraud? I suppose it’s possible, but I’m inclined to believe otherwise.

I’d be interested to see the longer dated follow up results.

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TO ALL!!!

WTF is it soup yet?

Good Luck and Good Health.

j-o-h-n Wednesday 03/28/2018 6:06 PM EDT

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Wondering, since grapefruit is not to be consumed with Xtandi, implications of taking MCP? Anyone have any info on this? Can't find anything out on Xtandi drug interaction with it (MCP). Thanks.

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Theoretically, the product consists entirely of pectin, an indigestible carbohydrate that is not taken up in the 'first pass' to the liver. The carb chains, which are normally too long to be taken up from the gut, have been chopped up (modified) so as to pass into the circulation, but should have no effect on the liver (or drug metabolism).

-Patrick

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Many thanks!

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