Case Report Stage IV Endometrial Cancer: Good News from Marcos

During this holiday, I was very happy to read good news from Marcos (a visitor of this website) regarding the treatment outcomes of his wife, suffering from stage IV endometrial cancer.

Here is a short summary extracted from the e-mails Marcos sent to me:

Status before the treatment, before May 28:
–  My wife’s tumors are found in the vertebra L2, bone and soft tissues around them.Size 6x4x5 cm.Lungs: about 14 very small nodules,the largest 1.2 cm, another 0.9, rest less than 0.4 cm
–  The tumor that gives problems is that of the vertebra L2 by its growth toward the spinal canal
In the analysis of tumor tissue (similar to foundation one)the mutations found were PI3K, PTEN, ESR1, and CTNNB1
– The state of my wife is very good, can travel, walking, cycling, does not appear to have this terrible disease, her capacity for fight and her desire to live are incredible. Despite the setting of 5 vertebrae in his back from the last operation.

Results reported on July 26:
–  The intensive treatment is giving a good result. reduction of tumor markers of 240 to 80. Destruction of half of the 14 lung nodules, with size reduction of the two largest. reduction in size of the lesion of the vertebra L2.

The treatment:
Part of the implemented treatment schedule was shared by Marcos here. The idea of his approach was to build an extensive treatment approach in order to increase the chance of success of the chemotherapy. This was done together with a medical doctor and they succeeded. Next to the chemotherapy, the treatment schedule included a few other substances expected to exert a strong pressure on the cancer cells, including glycolisis inhibitors such as 2DG intravenous and Salinomycin intravenous, but also diet approaches such as 3 days fasting before chemotherapy and Ketogenic Diet.
Marcos allowed me to publish his complete treatment schedule, but in order to mantain the safety of this website, if anyone is interested in knowing the details I think it’s best that you contact Marcos.

In my opinion the key of this success were the following aspects:

  • Attitude: Positive behavior, belief and expectation of Marco’s wife is essential
  • Coherent intravenous treatment: Correct type, dose and timing of additional intravenous treatments next to chemo
  • Coherent support for core treatments: Fasting before chemo, keto diet, and several other drugs and supplements used

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

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26 thoughts on “Case Report Stage IV Endometrial Cancer: Good News from Marcos

  1. Marcos- I am very happy to hear of your success, may your battle continue to be successful. Daniel, thank you for providing the resources to make successes possible!

  2. I am impressed by the good stuff that Marcos was able to buy for his wife, but I have a couple of observations, just to clarify the targets of the treatment, and maybe a couple of suggestions:
    – mutation PI3K means PI3K (part of the classic oncogenic pathway PI3K/AKT/mTOR) is aberrantly activated; the compounds listed there in theory can inhibit PI3K, even in synergetic combinations, but may not be enough, in comparison with a dedicated inhibitor; from my experience, Apigenin can worsen the blood formula, in my father’s case it didn’t help against the cancer; if you want to use Vit E, then use the Tocotrienol form, not the common Tocopherol, which may antagonize chemo;
    – liposomal Tetrandrine is a very good choice, Tetrandrine (new to me) inhibits many oncogenic signals, including beta-catenin, which is linked to the CTNNB1 mutation; Itraconazole may also inhibit beta-catenin; but there may be a problem, by inhibiting beta-catenin, the osteoclasts are stimulated; while Tetrandrine seems to act against osteoclasts, you might want to consider adding Zoledronic acid, against the spinal metastasis, if it is deemed osteolytic; there are a couple of articles about the use of Zoledronic acid against metastases of endometrial cancer; BTW, it would be nice to know, for other readers of the site, where to buy liposomal Tetrandrine from, and how expensive it is;
    – ESR1 is Estrogen receptor alpha, mutated means aberrantly activated, and Anastrazole should be inhibiting it;
    – PTEN tumor suppressor, just above PI3K, mutated means silenced, Tetranderine may upregulate it if it’s not silenced; if silenced, it may not help much; there are possible treatments against PTEN null (silenced) cancers;
    – the alternation of chemo and Salinomycin is a good choice, but I’m not sure about alternating 3BP and Salinomycin; maybe it would be worth trying simultaneous 3BP and Salinomycin, with lower doses; the reason is that Salinomycin is more cytotoxic under glucose starvation and hypoxia; I noticed that to counter the adverse effects from Salinomycin you use Amiodarone, I strongly suggest to switch to something else that would do the job; Amiodarone has a long half-life, and leads to the accumulation of several chemo agents, with potential lethal consequences;
    – instead of Avastin (Bevacizumab) you might want to consider Nintedanib; in various cancer trials it proved superior to Bevacizumab;

    1. Hi Ovidiu.
      Than you for your opinion,I very much appreciate your expert opinion.
      The problem you see in the administration of 3BP and SALINOMYCIN, is to increase the oxygenation for 3BP to be effective, may decrease the effectiveness of salinomycin?. Such as separarias in the period of 21 days?.Normally it is said that 3BP would serve to make effective salinomycin.That is to say there is that prime salinomycin with chemotherapy or with 3BP.The protocol of Daniel on 3BP and Salinomycin is the one that i have done.
      1.Nintedanib is not approved in Spain,your purchase in Sigma Aldrich is too expensive
      2.I don’t have access to protease inhibitors PI3K/AKT/mTOR pathway.DoYou know of one cheap and effective?.
      3Zoledronic acid. Don’t you think that its use could aggravate anemia which my wife presents almost constantly?.I’m scared of the osteonecrosis of the jaw. Could be used intermittently ,a month yes and a month no?.
      4.Already taking anastrozole two years ago I did not mention it in the protocol.
      5.Amiodarone will be deleted.
      6.Tetrandrine purchased powder to 98% purity in naturemmfg.com and mixed with high quality Empty liposomes of Enoch Solution.
      7.Please send me the studies of the use of zoledronic acid in endometrial cancer?.
      Please any other suggestions or possible treatment let me know.Your help is critical

      1. @marcos: 3BP has a short half-life of only 77 minutes, so applying Salinomycin the next day might be too late to benefit from the synergy with 3BP;
        The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions. PMID: 25152397
        With 3BP the problem is that, besides the short half life, by now (2+ months of treatment) the cancer may have downregulated MCT1…

        1. Nintedanib might be approved for pulmonary fibrosis, but not for cancer, this may change, so keep an eye on it;
        2. new synthetic inhibitors of PI3K/Akt/mTOR (not necessarily protease inhibitors like Nelfinavir or Ritonavir), tend to activate other survival pathways when used for some time; I still have to do more reading to understand the problem, so I can’t recommend one now; you are already using Metformin (sometimes only mTORC1 inhibitor, but in endometrial cancer full PI3K/Akt/mTOR inhibitor) and Tetrandrine for this purpose;
        Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling. PMID: 29182407
        Involvement of PI3K/AKT/GSK3beta pathway in tetrandrine-induced G1 arrest and apoptosis. PMID: 18437054
        You might want to replace Resveratrol with Pterostilbene, but you’ll have to import it from the USA, it’s scarce and more expensive in the EU;
        Pterostilbene, a natural phenolic compound, synergizes the antineoplastic effects of megestrol acetate in endometrial cancer. PMID: 28986550
        3. About ZOL, I don’t know, I suppose it might worsen anemia; you could check for low vitamin B12 levels, because of high dose Metformin, as a cause for anemia; osteonecrosis of the jaw is a more frequent for those with lots of teeth problems;
        4. I saw Anastrazole listed by you, and is probably doing its job;
        5. Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity. PMID: 27868228
        6. I tried searching with Google for naturemmfg.com and Enoch Solution Liposomes, but found nothing; so after some tweaking, came up with http://www.naturemfg.com/products/plant-extract/tetrandrine/ and http://www.enocpharma.com/?lang=en
        7. An Unusual Solitary Metatarsal Metastasis from an Endometrioid Endometrial Adenocarcinoma. PMID: 26193447

        Last, you might want to try Telmisartan, a cheap tumor stroma disrupting agent and a PI3K/Akt inhibitor, it synergizes with liposomal Docetaxel against a lung cancer Kras mutant in a mouse model. It may also synergize with the liposomal Tetrandrine, if Metformin hasn’t already disrupted tumoral stroma;
        Tumor stromal disrupting agent enhances the anticancer efficacy of docetaxel loaded PEGylated liposomes in lung cancer. PMID: 27171485

        1. Hi Ovidiu.
          I will try to apply salinomycin half an hour after 3BP,and to prevent the closure of the MCT1 line with paracetamol,EWOT etc.
          Can i replace itracozanol by a statin as lovastatin that increases the expression of Pten.
          In fact the two links to the pages of sale of tetrandrine and Empty liposomes are correct.
          I can access easily pterostibeno.
          Telmisartan will work just as well without the addition of doxorubicin?.
          I do not think it is wise to apply together lovastatin and zoledronic acid,according to your experience which it would be more appropriate?.
          I have access to celastrol known inhibitor of HSP90, we use together with Phlorizin to enhance the effects of hyperthermia that we are going to apply soon. What do you think?..
          Thank you for your opinions

          1. @marcos: Daniel made his point, that 3BP can inhibit glycolysis for a longer time than suggested by the short half-life, and that’s why doctors use the alternate day regimen, so better keep the current schedule;
            Telmisartan was suggested because the tumoral stroma could impede the delivery of many chemos, including the liposomes loaded with Tetrandrine;
            About the simultaneous application of ZOL and a statin, I wish I had a sure answer… there are pros and cons…
            A HSP90 inhibitor should be synergetic with hyperthermia, but the response to HSP90 inhibition is upregulation of HSP70;

            Last, do you have a way to check that the stuff you bought is really what you paid for, and that it was stored and transported properly, so it is still >90% effective when used by the patient?

            1. Hi Ovidiu.
              With regard to 3BP ,salinomycin and phlorizin i have total confidence were bought in SA. With regard to tetrandrine I bought at other times to this provider and accompanied by a certificate which includes storage temperatures that do not exceed 5 degrees.

            2. Hello Marcos.
              I’m very interested to use tetrandrin. I’m looking it for my dad since some time and I haven’t find a supplier. I have checked the web site where you bought it : thank you very much for this advice, I will write to them.
              But before, I want to ask you about the dose you use, when in the day (at what time), during or after meals…
              I have tried to understand how you encapsulate it in lyposomes, but I can’t understan: please can you explain me this step ? It’s mandatory or it can be used like this (even if it would be less effective)?
              Thank you in advance for this valuable information and good luck to you. I hope with all my heart that your wife’s condition will improve.
              Best regards,
              Dess

        2. Ovidiu, there is a difference between half-life of a drug and it’s intracellular action. Once inside the cancer cell, 3BP will act for several days. I’ve seen that on CT scan. So in my view, there is no problem with using other drugs the next day when targeting synergy between 3BP and the second drug. It may even be better to use the second day and not first in order to give time to some process in the cell to take place. That is why others such as US doctors using the combo of Sal and 3BP and reporting good results, used the combo in alternative days. Instead, I would better combine 3BP with 2DG during the same day and Sal and 2DG the other day. Kind regards, Daniel

  3. Hi guys!

    I have kept in touch with Daniel for months and my friend Marcos. My lack of time has prevented me from participating in the forum.
    My mother is having new growth of glioblastoma (diagnosed in 2015)
    We are using the same 2DG metronomic protocol as Marcos. Currently it seems that everything is stable.

    I will share our treatment line. Any suggestions will be appreciated:

    – Nanothermia 2 times a week at 120w
    – 2DG Metronomic once a week at 3grs. (3ml / h.) Combined one day with nanothermia
    – 80mg temozolamide combined the two days of 2DG
    – 600 mg of ribavirin every day
    – 200 mg celecoxib every day
    -1700 mg metformin every day
    – 10 ml empty liposomes all days (20ml in nanothermia days)
    – 100mg canagliflozin combined 1 day with nanothermia
    (distanced 48 hours from 2DG)

    I am studying taurolidine …. and a peptide vaccine directed to the PTEN mutation

    Daniel suggested me:

    – Besentabs but they can also help reduce the acidity around the tumor and that may be good for glyoblastoma that are highly acidic. Just that we need to clarify the impact on the absorption of temozolamide.

    – Add another cycle of metronomic 2dg in the week

    -Add another mitochondria inhibitor next to Metformin like Atovaquone

    -Add an MCT1-MCT4 inhibitor like Ibuprofen if possible, to reduce the lactic acid export that may result following the use of Metformin

    -Use other glycolysis inhibitors during the days my mom is not on 2DG. One that is accessible is Vitamin C in high dose, but you can try to search for other glycolysis inhibitors.
    If not, maybe you extended the use of canagliflozin to a time closer to 2DG admin but not overlapping that ……………………….. ……….

    I hope to participate in the forum!

    Best regards to all

    1. Hi Manuel,

      Thank you so much for taking the time to write this comment. I understand how difficult it is as you have so much to take care of, including taking care of your dear mom and working full time as the same time. So please use your time for that instead of spending time discussing on this website. What i only ask from you and others with whom I communicate by e-mail is that when there are general questions (not personal), please ask them on this website from time to time so that others can benefit from the related discussion. This is because lately I spend most of my time answering e-mails and calls, and as a result I have no more time to reflect the learnings here on the website so that others benefit.

      I would also like to add again that all the ideas and knowledge I share with you or others (including that going through private communications) goes with the Disclaimer on this website. Everyone has to use that as input only while discussing with their medical doctor the best approach in line with patient’s status, and should not replace the medical advice.

      Beyond that, I am happy to hear about the fact that your mom is doing better and she is now in a stable situation since you implemented approaches to support chemo, which as I understood was not anymore effective prior to that. I very much think 2DG metronomic plays a major role in that outcome.
      Indeed, I think Taurolidine is a treatment approach that is relevant for glioblastoma, but it requires an intensive treatment.
      Increasing slightly the frequency of 2DG metro may be an easier approach that could help.

      Kind regards,
      Daniel

    2. Hi Manuone, my father-in-law is a long term GBM survivor, for almost 16 years. In his case Tamoxifen + CCNU worked (after regrowth during temodar). He’d also take Melatonin(15mg) and antineoplastons orally. This supplement isn’t for sale any longer but phenylbutyrate is basically the same thing. Royal Jelly has some phenylbutyrate btw.

      1. Thanks Johan! Very helpful! I am glad to hear your father in law is well following these combos! Very good reminder regarding Phenylbutyrate which I also like it. It’s very expensive. A cheaper option could be from China but its challenging for most to find a trusted source. Do you have a specific source that its both fair quality and cheaper?

      2. Thanks Johan, for your response via the e-mail. I do not know why your comment is not published. I checked the spam and your post is not there. So here I will post your response and I hope in the future you will be able to post your comments (maybe you need to login first):

        “Hello Daniel, I’ve been trying to post a response on the forum but can’t get it to go through. So I’m sending it here. Have a great day! J

        Hi Daniel, here’s a good source to buy S. Phenylbutyrate: http://www.spb11.com/order/
        Note this is for “research only”.

        An alternative is to have the drug prescribed off-label, for Urea Cycle disorder.
        Some health insurance companies consider the drug necessary for treatment of malignant glioma, for example Aetna.
        http://www.aetna.com/cpb/medical/data/200_299/0240.html

      3. Hi Johan! Thanks for your comment. I find interesting tamoxifen adjuvant to temodal or lomustine with an “acceptable” toxicity …..
        Glutamine´s inhibition with sodium phenylbutyrate seems to me very important and would be synergistic to 2DG metronomic
        Does the natural glucosamine supplement perform the same function?

        https://www.mistrys.co.uk/ammonaps-tablets-500mg-250-pack-94273.html <<<<<<<<<<<< buy online sodium phenylbutyrate

        Could you tell me the doses your father-in-law use please?

          1. Hi Johan – Not sure if what I posted below was as a reply to you, so I’ll repeat.

            Can you clarify the dosing of antineoplaston for your dad? Would you guess a similar dosing of sodium phenylbutyrate would have comparable effects? For example, if your father in law could not access antineoplaston, what dose of sodium phenylbutyrate would you expect he would use?

            Thank you!

            Jessica

            1. Hi Jessica,

              A10 antineoplastons is a 4:1 mixture of phenylacetylglutamine(PG) and iso-phenylacetylglutamine(Iso-PG)

              Sodium Phenylbutyrate(SP) is metabolized to phenylacetylglutamine, however I don’t know how much PG you get
              from one gram of SP.

              My father in law took 18 A10 pills a day, which amounts to a dose of a 3.15 gr/day of A10. There was never a
              need to reassess the dose because after one month an MRI showed a small decrease in the tumor. So he just
              continued taking A10, with the chemo(CCNU), tamoxifen(40mg/day) and melatonin(15mg/day), until the gbm was
              gone (6 months).

              My guess is that 4 to 6 grams of SP could be a good (starting)dose.

              A recent study found that in Glioblastoma “inhibition of caspase-3 causes the microglia to stimulate the tumour
              cells instead of attacking them”. (Nature Immunology, September 2016 DOI: 10.1038/ni.3545).

              Interestingly, SP is a Caspase 3 activator.

              Since I mentioned Melatonin I have to add that Mel can inhibit caspase 3 activity. Meaning melatonin could
              potentially make matters worse. In spite of this, several studies show the benefits of using melatonin in treatment
              of gbm. One recent study suggests melatonin alters gbm stem cells (Chen et al. (2016) Melatonin Inhibits Tumorigenicity of Glioblastoma Stem-like Cells via the AKT-EZH2-STAT3 Signaling Axis).

              Hence the importance of combination therapies, and chosing the right combos. The result of using both an inhibitor
              and activator simultaneously can be either zero, inhibition or activation. Some drugs or natural compounds may be
              beneficial in one way and detrimental in another way. If you can cancel out the negative by combining with another
              compound, that could potentially make all the difference.

              All the best!

  4. Hi Johan – I’ll post my question here at the end as well, since it flows better. Can you clarify the dosing of antineoplaston for your dad? Would you guess that a similar dose of sodium phenylbutyrate would have comparable effects? For example, if your father in law could not access antineoplaston, what dose of sodium phenylbutyrate would you expect he would use?

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