Immunotherapy in Switzerland

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mpbser
Posts: 953
Joined: Wed Apr 19, 2017 11:52 am

Re: Immunotherapy in Switzerland

Postby mpbser » Thu May 09, 2019 9:43 am

“I'm not sure I would consider rp's approach alternative medicine.” Exactly. It isn’t.
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
low grade
1st primary T3 N2b M1a
Stage IVA
8/17 Sub-total colectomy
2nd primary 5.5 cm T1 N0
9 of 96 nodes
CEA: < 2.9
MSS
Lynch no; KRAS wild
Immunohistochemsistry Normal
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly bled to death
6-7 '19 5FU 4 cycles
NED

rp1954
Posts: 1853
Joined: Mon Jun 13, 2011 1:13 am

Re: Immunotherapy in Switzerland

Postby rp1954 » Thu May 09, 2019 5:59 pm

Pyro70 wrote:[rp1954] in numerous cases extolled the benefits of CIM here and in other threads said it “knocks the socks of FOLFOX”.

... knocks the socks of FOLFOX appears to be Pyro70's attempt to paraphrase my views. I did not literally say that (search my ID).

A better summary of rp1954's view(s):
CIM alone is a treatment component. CIM has been used in formulations against CRC with and without 5FU, treatments whose benefits appear to be strongly correlated with a combined pair of cancer biomarkers, CA199 AND CSLEX1 (not the other CD15s markers, aka sLex). Properly used, the metronomic 5FU+CIM formulations do not have the degree of instant, cumulative, permanent, or severe adverse side effects typically associated with Folfox.

Partial or root treatment formulations of 5FU + CIM, have published reports of survival benefit to stage 2, 3 and 4 colorectal cancer in prestigious medical journals. A series of papers, by more than a dozen Japanese MD-PhDs over 20 years, related to Matsumoto (2002), showed statistically significant, extraordinary survival benefit out to 10 years, for those CRC patients with cancer tissues marked by both CA199 AND CSLEX1, ++.

The Metronomic 5FU (derivative UFT) treatment component has long found favor with aged, fragile, partially DPD inhibited patients, and patients weeks closer to surgery. Likewise metronomic 5FU + CIM does not have the severe adverse side effects for oxaliplatin allergic patients. There are other medical journal published reports of medical benefit by adding leucovorin to metronomic 5FU, and for metronomic 5FU + PSK + CIM.
------
Incidentally, rp1954's wife was treated for 4 weeks with 1600 mg CIM, with high dosages of other immune and anticancer supplements prior to her first surgery for CRC. She experienced a massive immune reaction with localized complete remission to her peritoneal area despite an incomplete resection and bleeding, much destruction to tumor deposits, regional mets and primary sigmoid colon cancer. Her surgeon and pathologist had never seen anything like it. Her tumor tissues are marked by CA199 and CSLEX1.

Subsequent treatment with metronomic UFT (5FU) + CIM and even higher doses of supplements held her multiple para-aortic lymph nodes in check for a year until surgery. Her UFT + CIM chemotherapy with IV vitamin C and supplements was mild enough to use within 24 hrs of major surgery, before and after, for the para-aortic lymph nodes at the aorta. Her surgeon despaired over the extent(ions) of the para-aortic cluster but recommended "chemo forever". An oncologist, who was unfamiliar with her supplements, predicted that she "will soon burn up her bone marrow" on UFT+LV+ASA+CIM. After 8 years chemo and supplements, her WBC was 5+, Hgb 14 - 15, platelets ca 150 on chemo.

Her metronomic chemo evolved and eventually dropped most of the CIM after some years. Her surgeon laughed at her after 5 more years when she blurted out that she "wanted to be cured", and she cried. She quit chemo at 8 years, almost a year ago, always able to play the piano with a full head of hair and no lost chemo days. Her doctors have no patients remotely alive like that. No folfox or avastin.
Last edited by rp1954 on Fri May 10, 2019 1:52 am, edited 8 times in total.
watchful, active researcher and caregiver for stage IVb/c CC. surgeries 4/10 sigmoid etc & 5/11 para-aortic LN cluster; 8 yrs immuno-Chemo for mCRC; now no chemo
most of 2010 Life Extension recommendations and possibilities + more, some (much) higher, peaking ~2011-12, taper chemo to almost nothing mid 2018, IV C-->2021. Now supplements

stu
Posts: 1613
Joined: Sat Aug 17, 2013 5:46 pm

Re: Immunotherapy in Switzerland

Postby stu » Thu May 09, 2019 6:47 pm

Hi ,

I just want to say I have no issue with what anyone wants to take I just fail to understand how anyone can accurately state the effects one agent has over another !!! How do you know what component caused the tumour regression !!

My own mother is ten years into a stage 4 diagnosis with only ever 12 cycles of chemo over two years . Nothing since 2010 apart from a lung resection . I make no claims regarding her longevity apart from feeling deeply grateful to whatever aspect of treatment caused the tumours to disappear off the scan . She literally took six cycles of chemo, her liver which had tumours the size of a small orange were no longer visible on her scan and her oncologist also was amazed and rarely saw a response of this nature . Some people are very responsive to chemotherapy . Had she added additional aspects to her treatment I often wonder would I think they contributed to her response. She never did so I know she is chemo responsive .
I just fail to see how anyone can separate what has caused the regression when more than one treatment is being used .

Other than that I wish her continued good health and many more years of happiness .

Stu
supporter to my mum who lives a great life despite a difficult diagnosis
stage4 2009 significant spread to liver
2010 colon /liver resection
chemo following recurrence
73% of liver removed
enjoying life treatment free
2016 lung resection
Oct 2017 nice clear scan . Two lung nodules disappeared
Oct 2018. Another clear scan .

rp1954
Posts: 1853
Joined: Mon Jun 13, 2011 1:13 am

Re: Immunotherapy in Switzerland

Postby rp1954 » Thu May 09, 2019 7:08 pm

… Some people are very responsive to chemotherapy .

Actually one of the whole point of our exercise is to be maximally responsive to an individual's chemotherapy - much less toxic with much more cancer inhibition, not random or average of disparate types. Precisely one of my criticisms of current practices about markers, panels, inflammation levels, and test frequency. This is part of why I keep harping on blood CA199 then tissue CA199-CSLEX1 - the Japanese papers imply that they might be a near quantitative marker for CIM matched to CRC, and lay it out.

Stu, absolutely one tries for added effects. Different components have different claims and common or characteristic effects attached to them. My wife's experiences, dosage changes, and tests technically can only be said to "be consistent" those various added claims. Although we modified LEF's formulation, I give a lot of credit to Life Extensions entire cancer, cimetidine and supplement articles in 2010 for over all description and delivery of those claims, including markers. Over time, we tested different parts with noticeable changes that imply the component(s) benefit by preturbation. Some will say "lucky" and have no idea about the technical problems solved to do that. They might as well say some bum named Armstrong stumbled onto the moon, and luckily got back alive.

The upper part of my 5FU+CIM statement is a fairly accurate technical summary. The wife part is part of my personal view.
watchful, active researcher and caregiver for stage IVb/c CC. surgeries 4/10 sigmoid etc & 5/11 para-aortic LN cluster; 8 yrs immuno-Chemo for mCRC; now no chemo
most of 2010 Life Extension recommendations and possibilities + more, some (much) higher, peaking ~2011-12, taper chemo to almost nothing mid 2018, IV C-->2021. Now supplements

rp1954
Posts: 1853
Joined: Mon Jun 13, 2011 1:13 am

Re: Immunotherapy in Switzerland

Postby rp1954 » Thu May 09, 2019 8:05 pm

Pyro70 wrote:… Everyone knows that in the adjuvant setting surgery is far more important than medical treatment. Most likely these patients were “cured” by surgery not CIM.

There were plenty of placebo deaths in Figure 3D, Matsumoto (2002), 80% mortality for the CA199 tissue marker alone, faaaaar more than the other non-CSLEX1/CA199 CRC types. The Matsumoto paper is abundantly dotted with statistically significant results like p=0.0001, p=0.001, p=0.0015, p=0.006, p=0.0026, p=0.0002.

You could see the same thing happen in a small FOLFOX trial, but you won’t because no one looks at small data sets that are potentially misleading for FOLOX anymore.

This is the part you do not get about a specific group targeted with near quantitative markers vs a normal unstratified chemo test. One rough calculation suggests you might need a non stratified test with about 9x more bodies, or more, to achieve similar significance but still with much less accurate patient targeting. I would hate my life being indifferently sacrificed like a little white mouse with inferior test design, with extra mortality risks, then ordinary patients receiving no superior options.

…. but ignore another trial (or weren’t aware of) that can be found with a 2 minute google search.

You promote that fresh little turd of a trial with systematic errors (clear ones and likely ones) with no statistically significant results on random errors (e.g. p = 0.92, p = 0.69, p = 0.59, p = 0.28) as if it were a deal breaker over multiple papers with 421 patients, with the characteristic "Y" and statistical significance. Your negative howl still misses the (non-significant) net positive benefit values for CIM, where you state this as if they were actually negative, with higher tx'd mortality !
Jeez, junk science indeed.

Then you say you need to “educate” oncologist on things like CIM therapy and are shocked that they aren’t aware of it. Yes, they likely aren’t aware of it because ...

… slow learners and journals' non readers get their CME credits over caviar and wine.

It’s not as simple as using a single small trial to guide decisions. That’s why there are guidelines to help make sense of various trial outcomes and identify the strongest / sufficient data.

There are more trials that reached significance and a clear meta analysis for CIM, especially sobering without the high mortality CSLEX1/CA199 targeting in the meta analysis. I might understand a temporary preference in guidelines, but an absence of secondary notes, and tissue based trials since 2002, is deafening. Really sickening when you, er, I think about it. Ditto for claimed "expertise" of the oncologists. Matsumoto showed about 65% of advanced CRC affected by high CSLEX1/CA199. CA199 data from UK and Australia suggest this is pretty broadly true. The Japan work also implies a good way to identify and treat an underserved high risk minority - the high risk, sLeX/A stage 2 patients, a lot of them with RAS/BRAF mutant cells - decisively, effectively and *nicely*.

One thing I do have to admit, is that current day Western patients, might have added risk factors that should be improved in reporting, or treatment, for future tests e.g. HgbA1C, LDH, hsCRP, vitamin D, or even weight.

But whatever, it really isn’t worth my time discussing with you because you seem hell bent on promoting weak/junk science.

A lot of imagined authority and knowledge you have there. With even a little cooperation from patients' doctors on initial blood CA199, and tissue CSLEX1 and CA199, patients could actually do more effective CRC science than their Big Med, pharm fed oncs have.

… Your support for the Swiss immune treatment that started this thread is another example of offering your support for a treatment without any evidence of efficacy.

I discussed a starting point for evaluation. I dug out and noted that their claimed CRC major response rate was only 35% instead of the best response rates claimed amongst other cancers, at 85%-100%. I noted the likely high expense and the long time needed for review. I thought I saw previous technology commercialization to a mainstream 3rd party (a big deal personel credit wise) as well as degrees and publications.

I did not automatically condemn the Swiss clinic for something that is biologically plausible, extremely interesting, and potentially useful in many ways if true. You seem to suffer from some kind of PTSD that this is the next Burzynski or the worst Mexican clinic and then launch into defamatory tirades. Show us the evidence, not just sheer speculation, world class conclusion jumping. I can see you blowing your wig if you had been in Switzerland in 1905 when that Einstein kid started publishing all those crazy papers!
watchful, active researcher and caregiver for stage IVb/c CC. surgeries 4/10 sigmoid etc & 5/11 para-aortic LN cluster; 8 yrs immuno-Chemo for mCRC; now no chemo
most of 2010 Life Extension recommendations and possibilities + more, some (much) higher, peaking ~2011-12, taper chemo to almost nothing mid 2018, IV C-->2021. Now supplements

mpbser
Posts: 953
Joined: Wed Apr 19, 2017 11:52 am

Re: Immunotherapy in Switzerland

Postby mpbser » Fri May 10, 2019 7:13 am

Thank you for taking the time to write this detailed response, rp1954. I am not familiar with the entire eight year story. For all I knew, your wife had stage iv with liver met(s?). I had not known about para-aortic lymph node involvement. The fact that she has done this well for this long without the typical chemo cocktails is truly remarkable.

Should be an inspiration to us all.

I pray and try with every ounce of my being that my husband will be cured with the best of both worlds in a similar way.
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
low grade
1st primary T3 N2b M1a
Stage IVA
8/17 Sub-total colectomy
2nd primary 5.5 cm T1 N0
9 of 96 nodes
CEA: < 2.9
MSS
Lynch no; KRAS wild
Immunohistochemsistry Normal
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly bled to death
6-7 '19 5FU 4 cycles
NED

Pyro
Posts: 305
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

Re: Immunotherapy in Switzerland

Postby Pyro » Fri May 10, 2019 7:46 am

If you’re smarter than oncologists, and near the level of Einstein, why not become an Oncologist? It’s a serious question, using your own words, not a defamation.
Aug 2015- Stage 4 CC with liver Mets(38/m)
Sep 2015- Avastin/Folfox/Iron
Dec 2015-Not liver surgery candidate
Jan 2016- Erbitux/Folfiri, 2nd opinion at MDA in TX
Feb 2016 -MDA liver surgery
Mar 2016 -30% of left lobe rem, PVE
May 2016 - 70% of liver rem
Jun 2016-Rad
Jan 2017-perm colost @MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Rad
Mar 2019 - Keytruda fail
Jun 2019 - FOLFURI
Aug 2019 - No more, quality time!

rp1954
Posts: 1853
Joined: Mon Jun 13, 2011 1:13 am

Re: Immunotherapy in Switzerland

Postby rp1954 » Sat May 11, 2019 6:13 am

For all I knew, your wife had stage iv with liver met(s?).

My wife has had three 6mm lung thingies and several larger liver lesions that were never biopsied. In the first year, one lung thingy disappeared, one turned to stone (we had kept her calcium level high and calcium deposition rate high for some months along with other chemo stresses), one just sits there. In the second year, after 2nd surgery and more potent immune stuff for longer, the liver lesions became chemo reactive and have waxed and waned or disappeared with formulation and marker variations.

Pyro wrote:If you’re smarter than oncologists, and near the level of Einstein,

I was comparing the Swiss clinic's radical outsider status, and its hypothetical possibilities, to the undiscovered status of young Einstein as a Swiss patent office clerk, right before he became famous. Sometimes things aren't what they seem, either direction.

… why not become an Oncologist? It’s a serious question, using your own words, not a defamation.

I'm a little past prime for med school on memory work etc and would finish a residency well past when most retire, or die. My dreams and interests were never for medicine. To be honest, in a different time and tribe, MDs were only 3rd or 4th on the totem pole if they were not dual status individuals. Oncology, oncologist stories, pre'70-'80s, 1980s, well, nevermind.

I might not easily qualify on formalities either. You know, I only had about half a year of chemistry lecture in high school, then later, got disgusted, left at 16, and never did graduate HS.
watchful, active researcher and caregiver for stage IVb/c CC. surgeries 4/10 sigmoid etc & 5/11 para-aortic LN cluster; 8 yrs immuno-Chemo for mCRC; now no chemo
most of 2010 Life Extension recommendations and possibilities + more, some (much) higher, peaking ~2011-12, taper chemo to almost nothing mid 2018, IV C-->2021. Now supplements

Pyro70
Posts: 156
Joined: Mon Jan 21, 2019 4:25 pm

Re: Immunotherapy in Switzerland

Postby Pyro70 » Sat May 11, 2019 10:34 am

rp1954 wrote:properly tissue targeted mode, metronomic 5FU-cimetidine has a reasonable claim of far better adjuvant OS performance than Folfox even today

From this thread

rp1954 wrote:If repeatable, this would be faaaaar better than Folfox or Xeloda alone for the same type of CA199+CSLEX1 marked patients.

https://coloncancersupport.colonclub.com/viewtopic.php?f=1&t=61840&p=488672&hilit=folfox#p488672

rp1954 wrote:...added cimetidine would have a good chance of having better stats than Folfox killing off escapees.

https://coloncancersupport.colonclub.com/viewtopic.php?f=1&t=62173&p=490858&hilit=folfox#p490858

I did search RP's threads, he's right, I didn't find that verbiage "kock the socks off":, but plenty of other claims that CIM outperforms FOLOX. I could have sworn though he used that wording, but NVM


rp1954 wrote:There were plenty of placebo deaths in Figure 3D, Matsumoto (2002), 80% mortality for the CA199 tissue marker alone, faaaaar more than the other non-CSLEX1/CA199 CRC types. The Matsumoto paper is abundantly dotted with statistically significant results like p=0.0001, p=0.001, p=0.0015, p=0.006, p=0.0026, p=0.0002

I believe you're trying to make the claim that the since the Matsumoto saw 100% 5-year survival for the CSLEX1 CIM treated subgroup and the trial was statistically significant that:
1. CIM is better than FOLOX (for this genetic subgroup) since FOLOX adjuvant treatment doesn't have nearly a 100% survival
2. Because the p value < .05 the the 100% survival must be due to CIM and not chance or another factor

Again you cannot compare relative effectiveness of agents without a direct comparison in the same trial. Keytruda vs. Opdivo/Yervoy for MSI-H cancer is a good example. Currently it is assumed that Opdivo/Yerov has a higher response rate by looking at their respective trials. But experts in the field will say we don't know this for certain yet since there hasn't been a direct comparison of these immunotherapy protocols

You also overstate what "statistically significant" means. In the Matsumoto trial there were 22 CIM CSLEX1 treated patients. 40% (~9) would have been expected to survive without treatment. So there were 13! "excess" 5-year survivors which you are basing your entire claim on. If the trial would have had 3 arms (1. CIM, 2. FOLFOX, 3. Control), we would expect the number of FOLFOX 5-year survivors to be >9 (assuming also n=22) and the difference between FOLOX and the CIM arms would be <13. We don't know if this difference would have been large enough to be statistically significant (ie. p<0.05). So the p values you state above are meaningless when making a claim of FOLFOX vs. CIM.

Another important point regarding Matsumoto. Yes, the results were statistically significant but it was still a very small trial (only 22 treated patients in your subgroup of interest with 13 excess survivors). p<0.05 only tells us that the difference between control and experimental arm is likely not due to a RANDOM sampling error ("reject the NULL hypothesis"). It does NOT mean there weren't systematic issues, such as a difference in patient population between the control and experimental arm. With a trial this small, it is all too easy to introduce systemic errors because the patients were just different (different tumor type/biology (e.g. right vs left, differentiation, MSI, etc.) , extent of disease involvement, surgical skill/luck). Remember the results depend entirely on those 13 extra survivors, there could easily have been a number of the 13 out the 22 CIM treated patients that had an inherently better prognosis than the control group average.
In summary this Matsumoto trial by itself is too small to definitively say CIM is an effective treatment and it doesn't tell us anything regarding the effectiveness of CIM vs. FOLFOX - a claim you've made many times. The trial would need be larger (and frankly the benefit would have to be shown in a second trial) before CIM therapy would be accepted as effective treatment and be included in evidence based guidelines. This is something Matsumoto acknowledged in his article, but you chose to ignore as you're advocating patients to use CIM:
Our study was so small a number scale that further large-scale study should be investigated to assess the effect of cimetidine to colon cancer with high expression of sialyl Lewis antigens.


rp1954 wrote:You promote that fresh little turd of a trial with systematic errors (clear ones and likely ones) with no statistically significant results on random errors (e.g. p = 0.92, p = 0.69, p = 0.59, p = 0.28) as if it were a deal breaker over multiple papers with 421 patients, with the characteristic "Y" and statistical significance. Your negative howl still misses the (non-significant) net positive benefit values for CIM, where you state this as if they were actually negative, with higher tx'd mortality !
Jeez, junk science indeed.

First, I don't promote this trial. I provided it as counter-evidence to the Matsumoto trial. I'm not claiming either trial is better or worse. I'm saying we don't know which trial to believe.
Second, this "little turd" of a trial was twice the size of the Matsumoto trial with 2x the number of CIM treated patients in the experimental arm (34 vs. 65 CIM treated patients in Matsumoto and Jameson respectively).
Third, you discount the trial because you don't like the results even though you haven't seen the full paper for the trial

rp1954 wrote:Your negative howl still misses the (non-significant) net positive benefit values for CIM, where you state this as if they were actually negative, with higher tx'd mortality !

rp1954 wrote:The paper has the normal medical (mis)use conventions by not explicitly stating "significance" or "significiantly", so that a non-significant positive result is verbally reversed into a big negative.


Again you demonstrate a shocking lack of understanding of statistics. Amazingly you also think that you know better than the medical conventions established through probably a hundred of years of rigorous science. Any first year statistics student can tell you that with a large p value, having "positive" results are completely meaningless and mean that the trial was NEGATIVE for showing therapeutic benefit in the experimental arm. It does NOT mean there was small benefit from the drug and "if you are really trying to keep patients alive", as you say, that you would give patients this drug. Further, in case it's not clear to you, the burden of proof is always on showing that an agents works, not that it does NOT work. That's a basic tenet of "do no harm" in the Hippocratic Oath.

I'm indifferent if one wishes to call RP's approach "alternative medicine" or not. He promotes CIM therapy as if it were a fact that it's an effective treatment without stating any caveats about the lack/limitations of the data supporting its use. It's clear that currently there is insufficient evidence for CIM's efficacy and his bold claims of CIM's superiority vs. FOLFOX are entirely without evidence. When digging into the details, he demonstrates a complete lack of understanding of basic statistics which is the foundation of assessing an agent's effectiveness in a clinical trial. Readers should note, RP's claims about CIM effectiveness is only ONE of many agents he promotes. Frankly, I haven't looked at many of the others in detail, but a cursory look makes many/most of them seem dubious at best. Even if no one is pursuing these therapies because of RP's prodding, at a minimum he is creating anxiety for CRC patients feeling their doctors are not giving them access to all therapies and sowing distrust between patients and their medical teams. Maybe you don't want to call this "alternative medicine", but I call it DANGEROUS.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

mpbser
Posts: 953
Joined: Wed Apr 19, 2017 11:52 am

Re: Immunotherapy in Switzerland

Postby mpbser » Sat May 11, 2019 3:40 pm

Again, "pyro70", you are being unfair to rp1954. He has never advised anyone to do anything like: don't do chemo, don't listen to your doctors, do CIM as a sole "cure," etc. yet you keep writing as if he has.

When my husband was first diagnosed, I found this forum quickly afterwards. One of the first things that I read about was CIM. I printed the Matsumoto article and brought it to one of my husband's very first doctor's appointments. He read it and prescribed it to him.

In my opinion, it is DANGEROUS to discourage people to think for themselves and to question "medicine" and that is what I think YOU do or is your intention at least. This is the bottom line: there is absolutely nothing wrong with adding CIM to one's regime. It's not "DANGEROUS" to recommend that people check it out.
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
low grade
1st primary T3 N2b M1a
Stage IVA
8/17 Sub-total colectomy
2nd primary 5.5 cm T1 N0
9 of 96 nodes
CEA: < 2.9
MSS
Lynch no; KRAS wild
Immunohistochemsistry Normal
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly bled to death
6-7 '19 5FU 4 cycles
NED

rp1954
Posts: 1853
Joined: Mon Jun 13, 2011 1:13 am

Re: Immunotherapy in Switzerland

Postby rp1954 » Sun May 12, 2019 6:16 am

Pyro70 wrote:
rp1954 wrote:...added cimetidine would have a good chance of having better stats than Folfox killing off escapees.


You twist my quotes some, except for the link. You leave out important specific conditions where and why a patient or doctor might compare CIM + mild drugs + supplements, or CIM + 5FU + additive options favorably. In this case, for a fragile patient,
natelaugh:...My dad is 79 with colon cancer stage 3b with T3N2AM0. … Should my dad do the chemotherapy?
natelaugh: My dad oncologist think 2 drugs FolFox for 6 months might be too much for my dad. He said that Oxaliplatin is very toxic and only add a few 2-3% to overall "Disease-Free Probability Following Surgery". He used this tool to get probability https://www.mskcc.org/nomograms
Do you think or anyone know that using only 5FU for mop up work/effective??
jpb571111: am T3N1. Started folfox in Feb 2019 4/12 cycles complete. My CEA level is .07( very low).
The f5u is very strong and alotta side effects. My onc recommended Folfox ( which sounds like the norm)
The side effects are horrible..nausea, fatigue, cold sensitivity, throat issues, constipation. This list goes on..
The f5u is a small portion that I get at the end and take home. Folfox is 3 parts.. not sure you can do just one..
My mouth issues are from the folfox..
Pyro: If his health is poorish anyway, no. I’ll say it, chemo is hell.
rp1954: 5FU works best when it is sensitized or aided by something else. In the literature, in other places, depending on the markers, these could be as mild as PSK correlated with the CEA marker, maybe IV vitamin C for both cancer inhibition and reduced side effects if his cancer is KRAS/BRAF mutant, and if his CA199 (cancer tissue, or pre-op blood samples) was not too low, added cimetidine would have a good chance of having better stats than Folfox killing off escapees.

Mild, targeted applications might be better than 5FU alone right? Especially nicer with daily oral UFT, a 5FU plan that has been recognized for decades overseas for fragile patients.

Also I am onboard chemo, sometimes helpful to Xeloda and Folfox patients, especially if they are nonCA199 (no CIM), or are folic acid challenged.

Pyro70 wrote:I believe you're trying to make the claim that the since the Matsumoto saw 100% 5-year survival for the CSLEX1 CIM treated subgroup and the trial was statistically significant that:
1. CIM is better than FOLOX (for this genetic subgroup) since FOLOX adjuvant treatment doesn't have nearly a 100% survival

Certainly that possibility exists for Matsumoto's patients but I think you miss two important points here.
First and very important, is the proximity that the CA199+CSLEX1 pair is to being a quantitative tissue marker for CIM action whether CR, 100% survival, or not in different settings. The marker can be as important as CIM OS.
Second, the ease of combination of 5FU+CIM with other mild or targetable adjuncts with low toxicity and better overall results, long term.
Pyro70 wrote: 2. Because the p value < .05 the the 100% survival must be due to CIM and not chance or another factor

No. That sounds like more red meat rhetorical bait. Pegging out has several interesting aspects that can include small test or particular population effects. However, neither should high performance be dismissed as all blind luck. It deserves intense examination and critical consideration to duplicate success elements. [crickets USA]

Pyro70 wrote: Again you cannot compare relative effectiveness of agents without a direct comparison in the same trial. Keytruda vs. Opdivo/Yervoy for MSI-H cancer is a good example. Currently it is assumed that Opdivo/Yerov has a higher response rate by looking at their respective trials. But experts in the field will say we don't know this for certain yet since there hasn't been a direct comparison of these immunotherapy protocols.

So you're busting my chops over a similar estimation situation ?
You sound very one sided, like many medical "us" vs "them" self-grading situations.
Pyro70 wrote: Another important point regarding Matsumoto. Yes, the results were statistically significant but it was still a very small trial (only 22 treated patients in your subgroup of interest with 13 excess survivors). p<0.05 only tells us that the difference between control and experimental arm is likely not due to a RANDOM sampling error ("reject the NULL hypothesis"). It does NOT mean there weren't systematic issues, such as a difference in patient population between the control and experimental arm. With a trial this small, it is all too easy to introduce systemic errors because the patients were just different (different tumor type/biology (e.g. right vs left, differentiation, MSI, etc.) , extent of disease involvement, surgical skill/luck). Remember the results depend entirely on those 13 extra survivors, there could easily have been a number of the 13 out the 22 CIM treated patients that had an inherently better prognosis than the control group average.
In summary this Matsumoto trial by itself is too small to definitively say CIM is an effective treatment and it doesn't tell us anything regarding the effectiveness of CIM vs. FOLFOX - a claim you've made many times. The trial would need be larger (and frankly the benefit would have to be shown in a second trial) before CIM therapy would be accepted as effective treatment and be included in evidence based guidelines. This is something Matsumoto acknowledged in his article, but you chose to ignore as you're advocating patients to use CIM:
Our study was so small a number scale that further large-scale study should be investigated to assess the effect of cimetidine to colon cancer with high expression of sialyl Lewis antigens.

rp1954 wrote:You promote that fresh little turd of a trial with systematic errors (clear ones and likely ones) with no statistically significant results on random errors (e.g. p = 0.92, p = 0.69, p = 0.59, p = 0.28) as if it were a deal breaker over multiple papers with 421 patients, with the characteristic "Y" and statistical significance. Your negative howl still misses the (non-significant) net positive benefit values for CIM, where you state this as if they were actually negative, with higher tx'd mortality !
Jeez, junk science indeed.

Pyro70 wrote:First, I don't promote this trial. I provided it as counter-evidence to the Matsumoto trial. I'm not claiming either trial is better or worse. I'm saying we don't know which trial to believe.

The two trials are very, very different and you yourself admit that NZ is not remotely "evidence" quality. The NZ trial's mixing in stage 0-1 patients liberally, who are usually not CA199-CSLEX marked, and the stage 4 pts, just dumps variation and noise into the results.
Also I am annoyed that the NZ trial staff don't use more recent papers' suggestions to try to maximize CIM etc response in the pre-op like we did - biopsy material, potentially direct observation of "neoadjuvant" response, and it cleaned up a lot of bad stuff for us without HIPEC. Poor NZ patients!

Pyro70 wrote:Second, this "little turd" of a trial was twice the size of the Matsumoto trial with 2x the number of CIM treated patients in the experimental arm (34 vs. 65 CIM treated patients in Matsumoto and Jameson respectively).

For the stage 3 patients alone, the NZ trial was not so much larger; just more variance, confusion and heterogeneity would be added with stage 0, 1, 2, 4 patients with Folfox inflammation, and inadequate stratification, see Matsumoto(2002) Figure 2B and Figure 3. Unrelated to these CIM papers, Folfox's inflammation and potential effects on PFS/OS were discussed on this board 9 years ago (Jscho, a prof, PhD from MIT). Inflammation disrupts immune processes, like with Folfox, many of the cimetidine targetable NZ patients.
Also Matsumoto was post op only, nominally daily oral 5FU, 2 weeks to 54 weeks. 12 months immunochemo
vs NZ's cyclical Folfox (which may randomize immune results with WBC collapse) ... 6 months chemo or less? and more immune damaging (weaker CIM effects, too?)

Pyro70 wrote:Third, you discount the trial because you don't like the results even though you haven't seen the full paper for the trial

The NZ paper is clearly not apples to apples, although one could analyze for potential basis changes. I can be a data junkie. I would say the NZ trial is not designed for maximum pre-op response, some obvious population differences, 1/10 the CIM, and likely immune systems seriously compromised by Folfox and inflammation.

To me, you're just using a confounded abstract that confuses my view to onlookers, more. NZ may raise interesting questions about Folfox, interactions or targets for an entirely new category of heavy chemotherapy+CIM trial vs the immune trials and immunochemo via daily oral 5FU with CIM. You appear unwilling or unable to recognize how big a difference that is between immunochemo and cyclical, heavy duty chemo.

The very first oncologist I met with in 2010, the most senior with the most pharma sponsors, I asked him about the possibility of a brief, or some optimum, Folfox induction and then switching to metronomic 5FU etc. He was clueless and uninterested.

This NZ abstract is the first oncological contribution in that Folfox vein I've gotten in 9 years. Thank goodness we were able to do so much more with other sources, data and less injurious solutions like mild drugs and therapeutic nutrients.

Perhaps someone could address your aspersions, drs or your self pleading and anxieties at another time.
watchful, active researcher and caregiver for stage IVb/c CC. surgeries 4/10 sigmoid etc & 5/11 para-aortic LN cluster; 8 yrs immuno-Chemo for mCRC; now no chemo
most of 2010 Life Extension recommendations and possibilities + more, some (much) higher, peaking ~2011-12, taper chemo to almost nothing mid 2018, IV C-->2021. Now supplements

rp1954
Posts: 1853
Joined: Mon Jun 13, 2011 1:13 am

Re: Immunotherapy in Switzerland

Postby rp1954 » Sat Nov 27, 2021 5:06 am

Trying to resummarize this cimetidine discussion for later readers
Pyro70 wrote:First, I don't promote this trial. I provided it as counter-evidence to the Matsumoto trial. I'm not claiming either trial is better or worse. I'm saying we don't know which trial to believe.

The two trials are very, very different:
oral immunochemo 5FU for stage 2-3 (Matsummoto, 1992) vs
heavy cyclical FolFox stages 0-4 for the NZ paper.

In essence P70 accused me earlier of post hoc pleading about cimetidine and Folfox. However we specifically addressed Folfox cyclicity, inflammation and damage points 11 years ago in this very forum, and we prospectively committed to oral immunochemo rather than Folfox+Avastin based on that understanding, enhanced with more modulations then and over time.

P70 admits that NZ is not remotely "evidence" quality with significance. The NZ trial mixed in stage 0-1 patients liberally, pts who are usually not CA199-CSLEX marked - therefore cimetidine adverse, and the stage 4 pts who aren't curative pts. These dump huge variation, adverse pts, and noise into the results.

Also Folfox's OS benefit over 5FU alone would reduce the apparent net CIM benefit of earlier tests. The inflammation/injury and cyclical nature of Folfox likely reduces their CIM immune benefits in this NZ data set. Nevertheless, the NZ survival (median OS) with biomarked CIM for Folfox did show some improvement, albeit not significantly due to a lot of (staging, chemo injury) variance in the test. In essence the NZ paper adds doggy doo to the apple pie and says the apple pie tastes bad.

I am annoyed that the NZ trial staff don't use more recent papers' suggestions to try to maximize CIM etc response in the pre-op like we did - biopsy material, potentially direct observation of "neoadjuvant" response, and it cleaned up a lot of bad stuff for us without HIPEC. We used a lot of supplements suggested by LEF.

For anyone thinking about CIM: it seems to work most or best early/earliest, especially in the days around surgery. If CA199 is above the median CRC level, say 19, It appears to work best for immunochemo before your WBC or organ functions are damaged by heavy chemo. I am not familiar with any RT data.
Lower CA199 is less benefit or no benefit, especially for CA199 under 2 - no benefit or possibly adverse.
Likewise, long term cimetidine committment should use the (hard to get) CSLEX1 marker also
In later years, as things evolve, celecoxib/Celebrex worked better for us.
We made immunochemo work for us by mutiple modulations incuding chronomodulation, with extensive testing.
watchful, active researcher and caregiver for stage IVb/c CC. surgeries 4/10 sigmoid etc & 5/11 para-aortic LN cluster; 8 yrs immuno-Chemo for mCRC; now no chemo
most of 2010 Life Extension recommendations and possibilities + more, some (much) higher, peaking ~2011-12, taper chemo to almost nothing mid 2018, IV C-->2021. Now supplements

User avatar
beach sunrise
Posts: 1033
Joined: Thu Mar 05, 2020 7:14 pm

Re: Immunotherapy in Switzerland

Postby beach sunrise » Sat Nov 27, 2021 1:49 pm

I take xeloda + celebrex. ca199 is at 7. ND has me taking CIM now for a few months at 200mg per day.
8/19 RC CEA 82.6 T3N0M0
5FU/rad 6 wk
IVC 75g 1 1/2 wks before surgery. Continue 2x a week
Surg 1/20 -margins T4bN1a IIIC G2 MSI- 1/20 LN+ LVI+ PNI-
pre cea 24 post 5.9
FOLFOX
7 rds 6-10 CEA 11.4 No more
CEA
7/20 11.1 8.8
8/20 7.8
9/20 8.8, 9, 8.6
10/20 8.1
11/20 8s
12/20 8s-9s
ADAPT++++ chrono
CEA
10/23/22 26.x
12/23/22 22.x
2023
1/5 17.1
1/20 15.9
3/30 14.9
6/12 13.3
8/1 2.1
Nodule RML SUV 1.3 5mm
Rolles 3 of 4 lung nodules cancer
KRAS
Chem-sens test failed Not enough ca cells to test

User avatar
beach sunrise
Posts: 1033
Joined: Thu Mar 05, 2020 7:14 pm

Re: Immunotherapy in Switzerland

Postby beach sunrise » Mon Nov 29, 2021 9:28 pm

Hmm, good question!
Maybe someone will answer.
8/19 RC CEA 82.6 T3N0M0
5FU/rad 6 wk
IVC 75g 1 1/2 wks before surgery. Continue 2x a week
Surg 1/20 -margins T4bN1a IIIC G2 MSI- 1/20 LN+ LVI+ PNI-
pre cea 24 post 5.9
FOLFOX
7 rds 6-10 CEA 11.4 No more
CEA
7/20 11.1 8.8
8/20 7.8
9/20 8.8, 9, 8.6
10/20 8.1
11/20 8s
12/20 8s-9s
ADAPT++++ chrono
CEA
10/23/22 26.x
12/23/22 22.x
2023
1/5 17.1
1/20 15.9
3/30 14.9
6/12 13.3
8/1 2.1
Nodule RML SUV 1.3 5mm
Rolles 3 of 4 lung nodules cancer
KRAS
Chem-sens test failed Not enough ca cells to test


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