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johan
(@johan)
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24/06/2020 1:55 am  
Posted by: @jcancom
The below is your comment from Jess' thread.
 
Thank you for this liposome cocktail citation.
Quite remarkable. The 4 natural products in the liposomal cocktail was
almost as effective as cisplatin in lung cancer.
 
This might be a reasonably applicable suggestion for dng050.
 
After you have been on forum awhile you start to see the same chemicals
endlessly being recombined: curcumin, honokiol, quercetin ... .
Update the formulation and things start to look quite interesting.
Helping those on forum to access these easier formulations using liposomes would
be a big step forward.
 

I’d start hitting the damned thing with a different chemo, and a combo of supplements:
Vitamin D3
Liposomal Curcumin + Berberine
Honokiol + Magnolol
Luteolin
Betulinic acid + Delphinidin
Citric acid
Sodium selenite
Resolvins(EPA, DHA and DPA)
Royal Jelly(has Phenylbutyrate) + Melatonin    ....

I'm very happy you're feeling better J, this forum needs the insight you bring to it. So yes, I totally agree that in order to make a quantum leap forward, we need easier access to the best formulations and combinations, you've mentioned a few, and with just some of these, patients could quite possibly experience great results.


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Jcancom
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24/06/2020 3:58 am  

dng050, probably the best way to understand what is happening is that the tumor mass is now able to establish mets everywhere. While this might not be visible on scans yet, the potential is clearly present now for that to happen. Stopping this spread as quickly as possible with a multimodal approach is the best strategy. This is exactly what the Turkish clinic has done with apparently extraordinary success.

Consider Jess' example: https://www.cancertreatmentsresearch.com/case-report-stage-iv-pancreatic-cancer-good-news-from-jess/?highlight=Jess      Look at the figure for the CA 19-9 marker, the first chemo round slowly brought down the cancer burden by ~95% from 11/1/2017 to 5/1/2018.  As soon as the chemo was removed for a chemo holiday, the tumor entered a near vertical growth stage. On the second line of treatment, Jess added (to second line low-dose chemo) in many of the metabolic approaches that we have discussed endlessly about on forum, metronomic 2-DG, sali, 3-BP, fasting etc.. The response was then dramatic. As long as you have a binding chemo treatment available (a front line therapy), then other approaches can amplify it from there. This is where we are at with our understanding now.

What is quite impressive is that clinics such as Dayspring can achieve large tumor reductions without a frontline chemo. We are not entirely clear how they can do this. They report on their website that their go to treatment is 3-BP with supporting treatments such as ketogenic diet etc. 

One thing you need to keep in mind is that with so many of the current treatments there is no all encompassing strategy involved. Once the first line treatment is ineffective, there is no logical basis for the next line; it is simply the next step in the treatment. With the metabolic approach, you can continue to think about the illness as it tries to evolve within the well-defined logic of its own metabolism. It is comforting to think in this way as there are only a highly limited number of escape routes available in metabolism: OXPHOS, glycoslysis, TCA, etc.. From the metabolic perspective cancer becomes increasingly cornered (while escape routes continue to exist) through time they seem to be closing. With traditional treatment approaches, once cancer has escaped containment, an entirely new treatment plan (completely unrelated to the previous one) needs to be started. There is no comprehensive strategy involved.    

 

Interestingly, what we keep finding with our readings is that metabolism is often the substrate for many of the current treatment ideas. We saw this with BRAF drugs in melanoma. There are very expensive (and effective) drugs that treat BRAF, though they too have shown to lose effectiveness through time. Yet, research has also found that BRAF tumors have strong connections to the metabolic ideas that we talk about here. It does not make sense to me why they have not tried a dual metabolic/BRAF combination treatment. With two complementary treatments there is the possibility that you could push down the tumor beyond its ability to rebound ( 1,000,000,000,000 cancer cells x 0.01 x 0.01 --> ~0). You don't want to only have 1 0.01 because then there are 100 times more resistant cells that are available to resist additional treatment; moving the numbers down as rapidly as possible seems the best strategy.  

 

In the article below, breast cancer cells were sensitized to tyrosine kinase inhibitors through metabolic interventions.  "Perturbation of metabolic pathways sensitizes TNBC to inhibition of receptor tyrosine kinases."    

https://pubmed.ncbi.nlm.nih.gov/28852500/


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Jcancom
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25/06/2020 12:15 am  

Here is an article that speaks directly to lung cancer as a metabolic disease. It is almost identical to what could be said for almost any other cancer; highlighting the commonalities that emerge when thinking metabolically. 

https://www.frontiersin.org/articles/10.3389/fonc.2019.01215/full

 

The problems that occur when approaching cancer from an individual mutant targeted perspective (instead of a metabolic approach) are daunting. 1-3% of lung cancer patients genotype ROS1. Mutation to G2032R [c.6094G>A (p.Gly2032Arg)], accounting for 41% of resistance then presents the possibility that cancer could endlessly mutate away from any response. Cancer could then branch off into hundreds and hundreds of separately genotyped varieties. It is possible that convergence to containment might occur though this is not certain.  

Article mentions second line treatment after occurrence of resistance:

"chemotherapy agent pemetrexed has been associated with an objective response rate of 40%–58% and a pfs of 6.8–7.5 months in various lines of treatment and is therefore a viable treatment option for patients with ROS1-rearranged crizotinib-resistant disease"

https://pubmed.ncbi.nlm.nih.gov/31548824/

 

Would be reasonable to check on PD-L1 expression.

"Of the 14 cases with ROS1 rearrangement, 12 (85.7%) showed PD-L1 expression and 5 (35.7%) showed high PD-L1 expression."

https://pubmed.ncbi.nlm.nih.gov/30475455/

 

Nonetheless, one can see how through time the targeted approaches typically lose effectiveness and then metabolic strategies eventually become almost unavoidable.


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johan
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25/06/2020 5:09 am  
Posted by: @dng050

@johan 
Yes, I agree. Everything I have read points in the direction that this disease must be treated with a multifaceted approach to have hope of being succesful, since it is a complex disease.
I am always on the look for good supplements to add to my brother's growing list, so thank you for the suggestions. The ginsenosides, in particular, seem very interesting.

D-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer

https://www.dovepress.com/d-limonene-exhibits-antitumor-activity-by-inducing-autophagy-and-apopt-peer-reviewed-fulltext-article-OTT

 


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dng050
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25/06/2020 8:57 am  

@jcancom:
Thank you for the article. I have noticed it before, but have not had time to read it in depth. Will do it now to understand the metabolism of this disease.

My brother tested for PD-L1, but was found <1%. So I thought that he would not be eligible for immunotherapy, but recently I have noticed that people with low expression of PL-L1 have shown good response to immunotherapy.

The SOC in Norway is, unfortunately, that it is only one available TKI for NSCLC ROS1. Other places, such as in the U.S., I have seen people go from one TKI to the another and for many years have treated their disease like a chronic one. But this line of treatment is not accessible in Norway, so after crizotinib we must be prepared for chemotherapy (which I am afraid of). 

It is an interesting point you are making regarding the risk of mutation making it harder to treat the disease. This is EXACTLY what I am afraid of. If we wait too long, the TKI will not be able to contain the cancer. So I thought maybe the best angle to attack this is to let the disease stabilize a couple for months (my brother was diagnosed primo May 2020), before we try out the metabolic approach. But on the other hand, I am afraid that attacking the beast will wake it up (i.e. uintentionally upregulate other pathways for the cancer to develop resistance).

@johan:
I have put D-limonene on my list to check out, thanks. One thing which I am uncertain about is whether the induction of autophagy might not beneficial, especially since we have not started on any autophagy inhibitors yet (e.g. dipyridamole, hydroxychloroquine). 


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Daniel
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25/06/2020 3:13 pm  

@dng050

Hi dng050, 

If you are in Norway, you are relatively close to Germany, where in private context you can have access to many treatment options including low dose anti-PD1/PDL1. Some years ago that was at about 1000 euro/month (1mg/kg/month). I could not follow exactly where you are now and what you tried so far but if you like to have a phone call to exchange some ideas, we can have it sometimes next week.

Kind regards,
Daniel


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dng050
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25/06/2020 9:05 pm  

Dear @daniel, it would be great to talk to you and get some advice. We are based in Norway. The SOC of care for NSCLC ROS1 here is:

1. Crizotinib (TKI)
2. Chemo and/or immunotherapy

There is no 2nd (or 3rd) line TKI, e.g. lorlatinib, which I have seen is available for many in the U.S. and other places. It makes me sad to think that Norway is supposed to be an exemplary welfare state, but cannot afford to give its citizens the best care available. 

Currently, my brother is on crizotinib, which he has responded well to, except for the anemia which we are waiting for a discussion with his oncologist next Monday on how to handle. I am thinking about this line of treatment for my brother:

1. Crizotinib
2. Metabolic approach (repurposed drugs and supplements), e.g. COC protocol + dipyridamole, hydroxychloroquine, and LDN + hyperthermia + IVC -- to be used concurrently with line 1 of treatment
3. X (not yet decided)
4. Chemo and/or immunotherapy

No. 2 line of treatment should be done together with crizotinib, says my intuition. I am considering the AmberLife Clinic in Latvia and the Chemothermia Clinic in Turkey (credit @Jcancom). But I am also afraid to hasten the drug resistance, so I admit I am a bit uncertain here. The common sense tells me to attack the cancer while it is contained by the TKI. But from the ROS1ders Facebook group, I have seen wonderful examples of people being on crizotinib for 5+ years, effectively making this disease a chronic one, without them doing any adjuvant treatment. 

The 3rd line of treatment I would like to get ideas on. It should be a "big gun". From my readings of various types of treatments on your site and Facebook groups, 3BP with salinomycin seems to be a promising treatment. The practical challenge is, though, how to source it, formulate it correctly and lastly, but not the least, administrate it in the best possible way. 


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Daniel
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Posts: 777
26/06/2020 3:45 am  

Dear @dng050,

To plan the call please send me an e-mail (see contact). I have a relatively flexible schedule and can discuss at most of the times between 12:00pm and 12:00am Amsterdam time (which is the same as for Norway).

Please propose two options for next week and I will chose the one that is most suitable. 

Regarding ideas on anemia, please see this discussion https://www.cancertreatmentsresearch.com/community/lymphoma/please-help-with-new-strategy-refractory-hodgkin-lymphoma/paged/3/#post-3199

We can use the above summary as a base for discussion.

Kind regards,
Daniel


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Jcancom
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26/06/2020 7:44 am  

dng050, I am very glad that you can recognize the potential of metabolic therapy. It is so very confusing when starting out and often alternative therapies have minimal published evidence in the scientific/clinical  literature making it very difficult to consider non-conventional approaches. Chemothermia's results are so good that it makes it easy to see the logic behind metabolic medicine. 

If I were you, I would try to get to Turkey as soon as possible. Cancer typically gets progressively worse, and yet people will typically resist taking decisive action until after the illness has advanced. We have seen this time after time with cancer, people will resist innovative treatment for as long as possible; making it much less likely that something non-conventional could be effective. Considering how often alternative approaches are of side-effects it is surprising that people are not more willing to give them a try earlier than later. One consideration though is that COVID would make travel and possibly clinic interaction more dangerous especially for a lung cancer patient.

You could get up to speed on metabolic treatments by simply going to the clinic and letting them start up their protocol. The clinic's metabolic approach is very similar to what we have been talking endlessly on thread: DCA, 2-DG, 3-BP. It's all in their videos. Knowing exactly what to do to reach ketosis, fasting ... would allow a cancer response to occur now, not later. Why wait? At the clinic,you might ask on the side if they could offer you metronomic 2-DG, vitamin C, etc. . It would be an immersive learning experience in how to manage cancer taught by clinical experts. It is important to gain this knowledge as soon as possible: we have seen, however, that this is not usually what happens, people will only learn these important skill (if at all) after the illness advances.    

The idea that other treatments will induce resistance is not what they found with their metabolically supported chemotherapy. When you look at their survival curves what you see is that for the first year or so those patients who presented with more advanced disease were unable to be helped by the totality of the treatment force. Yet, those patients who had a higher ratio of treatment power : disease then often became  at least medium term survivors.

Decrease tumor burden early and gain an upper hand on the illness. This is not the typical staging plan for treatment. Patients will usually think that their current line of therapy is effective because their tumor markers are decreasing, yet underneath these numbers there is probably an exponential increase in a resistant clone though the bulk of the tumor mass is masking this. Removing the bulk of the tumor mass takes away the permissive environment conditioned for additional tumor growth. A large part of the clinic's success is related to treating the entire tumor mass with the add on metabolics not just those responding to the chemo (or perhaps to targeted therapy). Most conventional therapies are only focused on the top line markers while not acknowledging the emergence of a resistant clone. Only after a year or two once one line of treatment has been exhausted is it recognized that these other cancer cells have been accumulating.   

{It would be good to ask them about this, though. Have they treated those on targeted treatments? The articles they have published have talked about traditional chemotherapies: carboplatin/paclitaxel. It might not be known yet, though if they could achieve ~4 year average survival on the first line targeted treatment (say a TKI) and then another ~4 year average survival on the second line carboplatin/paclitaxel, then that would be a very large advance in treatment outcomes. The historical stage IV lung cancer control patients on standard of care had survival of ~8 months.}

I am very unsure about this idea that resistance could emerge by applying other therapies. Can anyone offer citations to support this idea?

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078107/

https://pubmed.ncbi.nlm.nih.gov/31527373/

https://pubmed.ncbi.nlm.nih.gov/32367884/

https://web.archive.org/web/20170421035758/http://chemothermia.com/category/lung-cancer/

go to youtube and type in "Chemothermia"


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dng050
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27/06/2020 3:48 pm  

Dear @daniel:
The proposed natural supplements to counter anemia look good. We have now bought barley grass juice powder. It is so green it looks like health personified. The angelica sinensis (female ginseng) looked very promising from what I read, but we are reluctant to try it since it can increase estrogen - which I understand is not beneficial for lung cancer (ref.).

My brother had to visit the ER yesterday evening because he felt lightheaded and dizzy, especially after standing up. His hemoglobin was further decreased, now only 10.5. It has decrease at a rate of 2 in two weeks time, which makes us quite worried. The ER doctor thinks it is due to crizotinib.

From my research, it seems that inflammation is a strong contributor to my brother's reduction in hemoglobin. At the ER, his CRP was measured to 12 (despite my brother's pescatarian diet and supplements. For instance, currently, he is taking 3 g of omega 3/daily. I have read promising articles on specialized pro-resolvings mediators (SPMs) in countering inflammation (ref.), so we have tried to nagivate the Internet to buy it.

Dear @jcancom:
I have made contact with the Chemothermia clinic to get more info on their treatment options and price level. Are they really providing 3-BP treatment? That would be wonderful. I was of the impression that it is very difficult to find 3-BP treatments from clinics today. 

I have not seen published articles stating that metabolic treatments can interfere with TKIs and thereby inducing resistance. There are just anecdotes, but we are gripped with fear in our situation to do anything wrong, in the absence of a professional to guide us - and very little empirical knowledge on the workings of TKIs and the development of resistance. Ref.

 


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Jcancom
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28/06/2020 3:35 am  

dng050, I am so glad that we have been able to reach you. I understand how extremely fearful one can be; there is an extraordinary amount of cancer research amounting to what seems like hundreds of millions of articles, many of which seem contradictory. Hopefully the posts on forum can help you to develop some clarity and calm. Thinking metabolically can be comforting. It does start to make a great deal of sense and ideas start to constantly connect up to other ideas within a closed system of thought. Most of the rest of the literature becomes fragmentary.

{Here are the metabolic maps. We have focused mostly on glycolysis/ OXPHOS on forum though there are a few others of interest as well.

https://en.wikipedia.org/wiki/Metabolic_pathway

http://biochemical-pathways.com/#/map/1

The power and breadth of the metabolic perspective can be seen from the article below. In this article, the what I can only guess (hope?) is the somewhat obscure enzyme--  serine racemase (SRR)-- can have a significant  influence on colorectal cancer growth. [ I was unable to find this reaction on the Roche biochemical pathways url above. I am worried that Johan will claim this prize.] Serine racemase helps to convert L-serine to D-serine and it allows the conversion to pyruvate. This backdoor method of producing pyruvate (a highly relevant metabolic metabolite) is actually that important? It is surprising, though it illustrates how powerful metabolics truly is. Serine is a non-essential amino acid. A chemically defined diet that did not include serine does not seem unreasonable.

https://www.nature.com/articles/s42255-019-0156-2   }

Oftentimes, language or culture stands in the way of clear and effective communication. Reaching out to Chemothermia and thinking in terms of seeking treatment earlier than later is highly rational. The pre-programmed default is to wait until there is deterioration. That is not rational. Cancer is relentlessly expanding and mutating. The sooner that you can debulk the tumor mass the better. With exponential growth, there is an exponentially increasing probability of new and perhaps even more challenging mutants arising. We have seen that ~95% of the tumor cells can be removed by a line of treatment, yet then the resistant strain that follows becomes even more of a challenge. In fact, we have seen that people then become locked into an addiction to their chemotherapy.

Embracing the challenge at the start of an exponential increase could make a substantial difference later. It is frustrating, though given the history of cancer treatment this is still more of a logical than empirical appeal. All the many millions of lung cancer patients to date have mostly followed the chemotherapy path and had life expectancies of ~8 months, in comparison to ~42.9 months reported in preliminary research from Chemothermia. The metabolic stress seems to be helping to contain the emergence of resistence. 

Engaging with the problem early also helps to avoid the drift that can happen with cancer. When you hear that the first line might give you a year without progression, there is a tendency to disengage.  However, knocking the markers down as quickly as possible focuses your attention to the next wave that is probably already emerging. Not doing so, merely gives you the illusion of success.  

We have probably spent too much time on forum contemplating the science instead of the psychology of cancer. The typical response that we have seen is that people will not make any decisive decisions until it is absolutely necessary, even then they will tend to delay. This is a near hardwired aspect of human psychology. I remember from the compass thread that someone was investigating 3-BP for their loved one who was in an ICU in relation to terminal end stage cancer. They were still unable to determine whether 3-BP were safe enough. If I recall correctly, they never were able to decide. This is human nature; people think that doing nothing does not count as a choice. With cancer that is not true; doing nothing means that cancer has an opposed path to expansion. 

 

Regarding Chemothermia, they do have videos online in which they discuss specifically the use of DCA, 2-DG, and 3-BP, though it is not entirely clear if these are currently in use at their clinic. They continue to mention on their website "infusions" as a main stay therapy and include the vague term "Anti-Glycolytic Treatment" under this heading. It would be worthwhile to clarify which "Anti-Glycolytic Treatment"s they use and whether they might be open to suggestions for example IV Honokiol. Clinics will have a set of standard treatments that they feel most comfortable with, though quietly on the side you might ask if they could personalize the treatment.

There is a financial consideration here. When patients start off in treatment, they will likely be willing to sign up for a full month cycle of treatment. This would be expected to cost a significant amount of money (~$ 25,000). Yet, as the illness advances it becomes more and more difficult to continue to finance treatment as their savings become progressively depleted, so patients might only be able to afford treatment on a day to day basis. Such selection might bias the reported results. D has talked about clinics who will charge ~$1,000 for a day of treatment. Paying by the day would seem to make a great deal of sense as it forces a rational appraisal of benefit on an ongoing basis. Usually when people write out large cheques, the incentive to incrementally produce value is lost. Nonetheless in this instance an immersive clinic experience does have a great deal of appeal. Learning how to live an anti-cancer lifestyle as soon as possible would be very useful.          

I have been thinking about what is the best next step. I am unsure whether it is Chemothermia or Dayspring. The advantage with Chemothermia is that they have reported considerable success with unselected sequential lung cancer patients. However, the problem that I can see is that they are locked into a chemotherapy model. They have noted that they are legally required to treat with chemo, even though they feel that a pure metabolic approach is desirable. This is where Dayspring has an advantage: they have a no chemo protocol. It is quite impressive that they have found a way to use a pure metabolic approach with 3-BP as their central therapy. Chemo would best be avoided for as along as possible. If you were to stay with your targeted treatment, then the metabolic protocol at Chemothermia might not be powerful enough to knock down the non-ROS1 cancer cells. These cells might only be vulnerable when being treated with their carboplatin chemo, while Dayspring has a no chemo philosophy. Dayspring reports a lung cancer patient whose tumor shrank ~55%. This is somewhat less than one would like, though it is unclear whether the treatment included 3-BP.

You will need to make your own choice on this, though Dayspring would appear to be a strong option. Chemothermia with their carboplatin and MSCT would always be there as a backup.

 

I am not sure whether we have noted this major set of articles yet from Nature about cancer genetics though it is of substantial importance. A genetic characterization of cancer is emerging: it is quite confusing. Nevertheless, it might be worthwhile to consider tumor genome sequencing. Current sequencing costs for a whole genome has already on specials breached $200. The cost is expected to continue to decline. Sequencing a non-cancer and a cancer cell could give very important information. Knowing for example, that cancer cells had mutations opening up MCT-1 would reveal that 3-BP could be effective. It could offer extremely powerful treatment insights. You could search out the entirety of the genome for weaknesses in cancer. As the article notes cancer cells (in particular lung cancer cells) can be very mutated and unstable. If this knowledge could be applied clinically, then it would turn cancer's strength into its weakness. A highly unstable genome would make cancer quite vulnerable. I read an article on this very idea with respect to dietary restriction. The idea was that removing non-essential amino acids could greatly stress cancer cells because the cancer cell would then be forced to have numerous functional enzymes (which would require functioning GENES! for these enzymes). Normal cells do have very well functioning genomes. Cancer cells not so much. the article below notes that sometimes entire chromosomes in cancer cells can shatter and then reassemble randomly. This clearly highlights how dysfunctional cancer genomes can be. It is difficult to imagine that a chromosome that was randomly reassembled could actually withstand a diet without non-essential amino acids. 

https://www.nature.com/articles/s41586-020-1969-6#Sec22

I encourage others on forum to start thinking genomically about cancer.  


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dng050
(@dng050)
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30/06/2020 9:42 am  

Thank you, Jcancom, for elucidating many of the complex issues and difficult dilemmas in how to approach cancer treatment. You have provided me with a lot of food for thought.

Yesterday we got some good news. The hospital took x-rays of my brother's chest, and the oncologist said that compared to photos from about 8 weeks before, the many spots on my brother's lungs have disappeared (like 80-90 %). So my brother has responded very well to the targeted treatment. But there is still a "line" which can be seen in his left lung. CT in August will clarify the situation more.

Although I appreciate the good news (which finally allowed me to breath a little bit after 8 weeks), I am aware of many peers achieving NED but only then to progress a couple of months later. Although I have not understood the mechanism behind this, especially not in mutated cancers, I have said to myself that I should not relax. On the contrary, progress should be followed by more treatments - because we now have the chance to "eradicate" the cancer by mounting more attacks.

Another good news is that my brother's hemoglobin seem not to have gone awry as we first suspected. Yesterday, it was 11.6, while a couple of days ago when my brother had to go to the ER due to dizziness and low blood pressure, it was 10.5. The oncologist suspected the blood drawn at the ER to be too thin and most likely has given an inaccurate result. So the decline seems to have stabilized around 11.5. I pray for the anemia not to progress negatively further, because that would complicate the targeted treatment.

So our strategy now is to continue with the targeted treatment, but also to research complementary treatments - in hope of pushing the cancer further back and to target cancer stem cells. Right now, would it make sense to take out the "big guns"? Or should we approach it more safe with treatment options like IVC and hyperbaric oxygen and repurposed drugs? The goal is to target cancer stem cells, to prevent recurrence, should me brother be able to achieve NED on the targeted treatment. 

While waiting for my brother's liver enzymes to normalize so he can restart on the COC protocol, he is taking these supplements:

  1. Turkey tail mushroom, 1 500 mg/day
  2. Melatonin, 15 mg/day
  3. Magnolia extract, 500 mg/day (we think it suffices with the Honokiol)
  4. Magnesium, 350 mg/day
  5. Calcium, 1 000 mg/day
  6. D-vitamin, 1 600 mcg/day
  7. Vitamin K2, 75 mcg/day
  8. Ursolic acid, 600 mg/day (uncertain whether UA can contribute to angiogenesis)
  9. Beta glucan, 1 000 mg/day
  10. Honokiol, 1 000 mg/day
  11. Milk thistle extract, 250 mg/day
  12. Modified Citrus Pectin, 15 g/day (started 17.06.2020)
  13. Omega-3 (600 EPA & 430 mg DHA), 2 000 mg/day (started 23.06.2020)
  14. DHA (250 mg EPA & 500 mg DHA), 1 000 mg/day (started 23.06.2020)
  15. Pycnogenol, 80 mg/day (started 24.06.2020)
  16. Cordyceps militaris, 3 g/day (started 25.06.2020)
  17. Barley grass juice powder, 6 g/day (started 26.06.2020)

Best regards,
dng050


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johan
(@johan)
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Posts: 450
01/07/2020 4:54 am  

@dng050

Analysis of glutamine dependency in non-small cell lung cancer:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469476/

UA in combination with Curcumin inhibit Gln: "decreased cellular uptake of glutamine resulting from the combined treatments with UA + CUR" https://www.nature.com/articles/s41698-017-0024-z

Phenylbutyrate is also a Gln inhibitor.

Theobromine, a metabolite of caffeine, inhibits angiogenesis. 

@daniel, I'm amazed why theobromine isn't used more often for angiogenesis inhibition. What's your take on this compound. I must be missing something.

 


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Jcancom
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01/07/2020 6:08 am  

dng050, this is great news!

I am especially glad to hear of your commitment not to relax but to take this opportunity to move forward.

We have spent so many years on forum trying to read through the literature to find the treatments that could help people (typically for those patients who no longer have conventional treatment options). Obviously it would be so much easier if clinical research including multiple phase 3 trials could be referred to in order to have complete knowledge. This is largely unavailable for most of the cancer treatments that we follow. This is medicine on the frontier where answers (often all of the answers) can only be guesstimated. If conventional medicine could provide these answers, then alternative medicine would be unnecessary.

However, currently a time arrives in which nothing further can be done for cancer patients within the context of science based medicine. It is probably a good idea to continually remind yourself that on the medium to long term horizon, these metabolic alternative are approaching. Conventional medicine is not allowed by law to step this far outside of the scientific method. Deliberately experiencing this high level of uncertainty related to alternative medicine is perhaps best done sooner than later: Metronomic 2-DG could be a good introduction. Many of thse treatments do not have comprehensive research that can be cited. Nonetheless as one reads through the vast amount of research, one begins to appreciate that it can be of utility; it can help to potentiate conventional treatments and it is becoming a standalone treatment modality. 

Your list of supplements speaks to your commitment to trying metabolic options, though there are a range of other metabolic ideas discussed on forum that you might find of value. For example, fasting and ketogenic diets have been recurrent topics. It will, though, take you some time to find the right mix. Traveling to a clinic is still something worthy of consideration as clinics have designed an immersive anti-cancer environment to pattern your behavior towards a low cancer risk lifestyle. Modern life is an apotheosis of everything that you shouldn't do in order to avoid cancer.  

Dayspring has a great deal of expert level cancer knowledge and I continue to be impressed that they consider 3-BP to be their top metabolic treatment. A top treatment needs to have monotherapy treatment power. Once this treatment is in place, then various others can be added to amplify the effect. It is a significant weakness of metabolics that these top treatments are so elusive as one typically would need to approach the safety boundary by aggressive dosing. A maximal dosing strategy was used with conventional chemotherapy. The lives of a great many patients likely were required to determine the line between too much and too little chemo.

Cancer stem cells are important, as you noted. Chasing after bulk tumor cells is more an illusion than reality. Having a biomarker for the cancer stem cells would be of great relevance, though I am unaware of such a biomarker. If there one available, then one could focus on actually controlling the driving force behind cancer instead of the downstream consequences. Yet, here again the metabolic approach is now reporting strong results against CSCs using OXPHOS and other mitochondrial inhibitors.

Keep up the great work!

Best Wishes, J

 

 

 

   


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johan
(@johan)
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01/07/2020 7:35 am  

@jcancom

I wonder if the the effect of the KD on cancer proliferation isn't, in part at least, b/c of it's effect on the thyroid(making the thyroid less hyper, or more hypo). If it was, it would be easier to target the thyroid then following such a strict diet.

https://cancerres.aacrjournals.org/content/64/7_Supplement/1024.2

 


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dng050
(@dng050)
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Joined: 2 months ago
Posts: 18
01/07/2020 8:15 am  

Dear friends,

I had a tough day yesterday. Only one day after the good news, my brother got the result of the blood work, showing that his liver enzymes (ALAT) were increased from 95 to 325 (normal range 30 - 70) in the last 12 days. The consequence of this is that the oncologist reduced his dosage of crizotinib to half (250 mg/day).

I fear that (1) the cancer will have a chance to progress during this period of reduced dosage or (2) that my brother cannot continue with crizotinib. In the latter case, I feel utter despair because there are no TKI available to us left.

I have not slept tonight. Sometimes life is incredibly sad.

Kind regards,
dng050


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Daniel
(@daniel)
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Joined: 5 years ago
Posts: 777
01/07/2020 1:41 pm  

Hi @dng050,

I am sorry to hear about you feeling bad and not sleeping but this could be good news as you may be able to maintain response to the current drug for longer time. That means you don't kill too fast the responding and so far dominant population. This may give you more time to put together a strong supporting strategy to increase the effectiveness of crizotinib.

Dealing with cancer is a roller-coaster. Don't let your energy be taken away by every event.

The liver enzymes will go back to normal relatively soon if you support the liver well. Btw, Hepamertz supplement from Germany can be good as well to support the liver. Here is a website where you can find pharmacies in Germany that has it available https://www.medizinfuchs.de/?params%5Bsearch%5D=hepamertz&params%5Bsearch_cat%5D=1

You just had great news a few days ago and that is the fact that matters. Enjoy that because that is the most important!

Kind regards,
Daniel


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dng050
(@dng050)
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Posts: 18
01/07/2020 4:04 pm  

Thank you, @daniel, for the soothing words. Hopefully, by reducing the dose, we can keep the main population in control, just like you say.  

Indeed, this is really a roller-coaster, it's "up and down" all the time. In quiet moments I long back to the life I had before cancer and miss the moments of carelessness.

I will take a look at the Hepamertz supplement. Looks like they do not ship to Norway, so I will have to search for other sources. I have also put my brother on more coffee (two cups a day) and beets in every meal, to support his liver. 

I am also pondering whether my brother should drop all his supplements (maybe with the exception of milk thistle and melatonin) to let the liver rest. But on the other hand, is this not exactly the time he needs more protection from the supplements? 

Best regards,
dng050 


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johan
(@johan)
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01/07/2020 4:59 pm  

@dng050

Sorry to hear this, I'd stop all supplements unless these are specific to supporting liver health and with approval of his oncologist. I agree with Daniel that sometimes what appears to be a negative ends up being a positive. That said the medication your brother is taking could be very harmful to the liver (case report) so I wouldn't worry about the cancer right now. IMO the health of his liver is more important in fighting cancer right now.


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Jcancom
(@jcancom)
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Posts: 345
02/07/2020 5:35 am  

dng050, I am sorry to hear this. I hope that you find the posts on the forum to be comforting because  coping with all of the ups and downs is a large part of effectively managing this illness. It is important that you do all that you can to care for yourself so that you can be an emotional support for your brother. Nevertheless, it is not easy to be stoic when such surprises arise.

Might you provide a more detailed description of the extent of the illness that your brother is facing? If you are expecting that he might go NED, then this would provide a very good opportunity to consider metabolic approaches.

Best Wishes in Difficult Times, J


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johan
(@johan)
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02/07/2020 6:32 am  
Posted by: @jcancom

 

I have been thinking about what is the best next step. I am unsure whether it is Chemothermia or Dayspring. The advantage with Chemothermia is that they have reported considerable success with unselected sequential lung cancer patients. However, the problem that I can see is that they are locked into a chemotherapy model. They have noted that they are legally required to treat with chemo, even though they feel that a pure metabolic approach is desirable. This is where Dayspring has an advantage: they have a no chemo protocol. It is quite impressive that they have found a way to use a pure metabolic approach with 3-BP as their central therapy. Chemo would best be avoided for as along as possible. If you were to stay with your targeted treatment, then the metabolic protocol at Chemothermia might not be powerful enough to knock down the non-ROS1 cancer cells. These cells might only be vulnerable when being treated with their carboplatin chemo, while Dayspring has a no chemo philosophy. Dayspring reports a lung cancer patient whose tumor shrank ~55%. This is somewhat less than one would like, though it is unclear whether the treatment included 3-BP.

You will need to make your own choice on this, though Dayspring would appear to be a strong option. Chemothermia with their carboplatin and MSCT would always be there as a backup.

@jcancom

Are there any verified and documented/pubslished case studies from Dayspring (dx,scans,mri etc) other then testimonials, this would be really helpful. I have an open mind, and have often felt as an utter fool as a result, but still it worries me to read this type of testimonials on Dayspring. I quote a from Dayspring's 3BP page: "This points out the need to find and address the potential causes of the cancer Some of the biggest we have seen are improper dental work, heavy metals, scars, nutritional deficiencies, low thyroid not picked up by the usual conventional blood tests and of course emotions from in utero and early childhood."

"and of course emotions from in utero and early childhood"?? What?? 

Low thyroid even seems to protect against cancer. (see my post above).

 

 

 


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dng050
(@dng050)
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Joined: 2 months ago
Posts: 18
02/07/2020 7:56 am  

@jcancom
I know I have to be strong for my brother. It is of much help to me to find support in this forum and on various Facebook groups. 

The medical history of my brother can be summarized as such:
- Had influenza or some other kind of infection in the summer of 2019; had some trouble breathing afterwards
- Developed a consistent non-productive cough
- Started entecavir for his hepatitis B in April 2020 due to viral activity (has had HBV since childhood)
- The doctors thought the cough was due to eosinophil pneumoni, so they started him on Prednisolone, but after biopsi of the lung concluded that it was - a devastating shock to us - lung adenocarcinoma, ROS1 positiv
- My brother also has asthma (since childhood), but no symtoms these days
- Started on crizotinib as targeted treatment medio May 2020
- No severe side effects, except for anemia and now elevated liver enzymes after 8 weeks on the drug

I am afraid my brother cannot stay on crizotinib if his liver enzymes continue to stay high. Normal range is up to 70, but it was 325 a couple of days ago. There are no other TKIs available in Norway for ROS1, so next line treatment is chemo and/or immunotherapy.

My hope was that my brother could stay a long time on crizotinib while receiving adjuvant metabolic treatment. But if TKI cannot be the main strategy anymore, I have to come up with a new main strategy. 

Best,
dng050


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johan
(@johan)
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02/07/2020 8:07 am  
Posted by: @dng050

 

My hope was that my brother could stay a long time on crizotinib while receiving adjuvant metabolic treatment. But if TKI cannot be the main strategy anymore, I have to come up with a new main strategy. 

Best,
dng050

The main strategy should be decided by your brother's oncologist. Let's not fool ourselves and others.


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johan
(@johan)
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Joined: 2 years ago
Posts: 450
02/07/2020 8:40 am  
Posted by: @dng050

- Started entecavir for his hepatitis B in April 2020 due to viral activity (has had HBV since childhood)
- The doctors thought the cough was due to eosinophil pneumoni, so they started him on Prednisolone, but after biopsi of the lung concluded that it was - a devastating shock to us - lung adenocarcinoma, ROS1 positiv
- My brother also has asthma (since childhood), but no symtoms these days
- Started on crizotinib as targeted treatment medio May 2020
- No severe side effects, except for anemia and now elevated liver enzymes after 8 weeks on the drug

Median OS for your borther's condition (who's dx is May 2020) is 51.4 months (95% CI, 29.3 to not reached) and survival probabilities at 12, 24, 36, and 48 months were 79%, 67%, 53%, and 51%, respectively. Your brother is dx + 1 month!

Those odd are better than my sister-in-law's ovarian cancer stage 4 who was dx's 4 years ago and she´s alive and kicking and enjoying life. And she mainly sticks to conventional treatment.

My advice: if needed try to find ways to improve the odds by adding to the standard treatment, don't think you are smarter than your oncologist(even the bad ones are still smart), and above all don´t put the life of your dear brother in the hands of people who believe cancer can be caused "in utero", meaning before birth. lol.

 

 

 

 


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dng050
(@dng050)
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Posts: 18
02/07/2020 11:17 am  

Dear @johan,

I really hope that my brother can stay on crizotinib for as long as possible, but that hope is in the sphere of uncertainty now. If the liver enzymes stay elevated despite dosage adjustment, my brother will not be eligible to continue crizotinib. The statistical OS would then be difficult to attain.

My original plan was to build adjuvant treatment around the TKI. If that is no longer possible, and the only treatment conventional treatment has to offer in Norway is chemotherapy (and not even in the form of chronotherapy), I feel other treatment options should be explored. I think in my brother's situation, chemotherapy should be the last treatment option.

As for the Dayspring clinic, I think it would be very risky for us to travel to the US in the current situation. I have also looked at the Block Center (US) for chronotherapy, but also due to travel risks and restrictions, I must now confine the explorations to Europe.

Best,
dng050


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Jcancom
(@jcancom)
Estimable Member
Joined: 3 years ago
Posts: 345
03/07/2020 4:42 am  

dng050, many of the posters on the forum arrive once there has been substantial progression which makes it more difficult to offer helpful suggestions to them. Yet, fortunately you arrived early and now you can carefully choose your best step forward. The opportunity to think carefully and rationally about your options should be a comfort to you. You have taken this opportunity and your logic to date has been impeccable. Slowing down and allowing regeneration to occur is not an unreasonable strategy now.

dnsg050, might you provide a more detailed mention of the specific location of mets and their sizes? I have been unable to find this information in your posts. 

Kind Wishes, J   


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dng050
(@dng050)
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Joined: 2 months ago
Posts: 18
03/07/2020 11:36 am  

Dear @jcancom,

I was very encouraged by the results from the x-rays, as I then for once had a moment of hope where I could truly see things ending positively for my brother. My line of though was that if the TKI could keep the cancer at bay, or even better get us to achieve NED, we could add adjuvant treatment in parallel (repurposed drugs + IVC + hyperthermia + rotating supplements) to get at the CSCs/senescent cells or whatever cell population which has not responded to the TKI. I have seen many peers have several good progression-free years on TKIs like crizotinib or lorlatinib, but to the best of my knowledge they have not tried to add adjuvant treatments while on the TKI before resistance developed. 

I was very curious about the size of my brother's tumors, seeing that many people on Facebook talked about this. But I have not found any information about this in the medical journals of my brother, nor have I received any info from the oncologist about this. (I asked him if the tumor had decreased, and apparently he said there are no tumors. But I might av misunderstood him). The spots in my brother's lungs were described as spread in both lungs, in the form of tree-in-bud. Recently, the x-rays showed only one remaining "thick line" in the left lung, while nothing could be seen in the right lung. The oncologist said we have to wait for the CT in August to get a more in-depth view, especially in the area between the lungs since this is not shown on the x-rays.

Fortunately, at diagnosis, my brother had MRI of the spine and the brain and no mets were found. We are cautiously optimistic because crizotinib has poor CNS penetration. 

On Monday next week, my brother will have new blood work to see how his liver ALT is. While praying for the liver enzymes to drop, I have tried to find various foods to aid in this, e.g. beets and coffee. Saw some people have had success with celery juice, but we are hesitant to try this due to the apigenin compund in celery is a CYP3A4 inhibitor (cf. section 5.1.2). Some people have also recommended lemon juice with warm water in the morning on empty stomach, but due to contradictory studies we have not started on this.

"Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects":

Few studies report the inhibitory effects of C. lemon on CYP3A4 enzymes. In 2001, Baltes et al. reported the first study for a potential interaction of lemon juice with hydroxytestosterone through inhibition of CYP3A4 activity. Lemon juice significantly inhibited 6-hydroxytestosterone production in an in-vitro model of human lymphoblastoid cell line (h3A4/OR)-expressing CYP3A4 activity [17]. In another in-vitro study, lemon juice inhibited CYP3A4-mediated hydroxylation of both testosterone and midazolam with IC50 values of 6.20 and 19.10 µM, respectively [18]. Contrary to these published reports, when sildenafil was administered with lemon juice in the current study, no significant changes on the absorption or elimination pharmacokinetics of sildenafil were observed. To our knowledge, we report the first in-vivo or human study regarding the effects of lemon juice on the pharmacokinetics of sildenafil.


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finnan
(@finnan)
New Member
Joined: 1 year ago
Posts: 9
03/07/2020 7:14 pm  

@dng050

You should consider milk thistle/Silibinin to support the liver:

Response of Brain Metastasis From Lung Cancer Patients to an Oral Nutraceutical Product Containing Silibinin: https://pubmed.ncbi.nlm.nih.gov/26959886/


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Jcancom
(@jcancom)
Estimable Member
Joined: 3 years ago
Posts: 345
06/07/2020 4:11 am  

finnan, thank you for your comment. You always have very insightful and valuable comments which I unfortunately have often obscured by my frequent posting.

Might you have an opinion concerning the potential for a metabolic approach for dng050? dng050 is in an unusual position for the forum in that he is far ahead of the time at which alternative medicine typically would be considered. Yet, even in this instance a metabolic booster co-treatment with the standard of care might be beneficial. We have seen how effective such co-treatments have been with others on chemotherapy. However, I am unaware of empirical findings for metabolics in targeted approaches. It would be helpful for those on forum to consider dng050's unique position and formulate an appropriate suggestion for him. 

Such a  co-treatment strategy would help contain the resistant clone cells, while at the same time reducing the non-resistant cells. Otherwise, mono-therapy targeted treatment would quietly allow these resistant cells to gain a foothold for months and months until the biomarkers were finally able to detect that a new cancer cell line exhibited exponential growth. Comments please!

J   

 


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finnan
(@finnan)
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Joined: 1 year ago
Posts: 9
06/07/2020 10:23 am  

@jcancom, thanks for the kind words. Please keep obscuring my comments with frequent posting!

They have reported some complete responses with the help of PI3K inhibitors + keto, so this is an approach worth investigating. https://news.weill.cornell.edu/news/2018/07/low-carb-high-fat-diet-may-boost-targeted-cancer-therapy

Olive leaf extraxt (East Park) could be worth considering for the Hep B and liver issues (anti-viral, anti-inflammatory and possibly has liver benefits).


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