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,
:...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 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" grading situations.
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).
Also Matsumoto was post op only, nominally daily oral 5FU, 2 weeks to 54 weeks. 12 months immuno
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 perhaps 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.
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.
I'll address your aspersions, drs/self pleading and anxieties another time.