Maraviroc: An anti-HIV Drug that Reactivates the Immune System to Fight Cancer

Introduction:

Recently, with the help of a reader of this website (Thank you, Jose!), I came across a very relevant article, Immunotherapy in metastatic colorectal cancer for the first time utilizes the innate immune system, published on the website of the German Cancer Consortium (DKTK).

macrophageThis article describes the results of a recent clinical trial running in Heidelberg, Germany using an anti HIV drug. (As a side note, we may remember that the first application of Salinomycin on humans was also done in Heidelberg.)

This phase I clinical study was conducted in 14 patients and was using the drug Maraviroc, an anti HIV drug known as a potent blocker of CCR5. While due to their mechanism CCR5 blockers are relevant to many cancer including that of blood, prostate, gastric, colon, breast, ovarian, etc. (Ref.), in this study the treatment was first applied on colorectal cancer patients with liver metastasis. Although I do not have yet the details of the study, the outcome of this study seems to be great as the scientists reported that following Maraviroc administration, the tumors in some of the patients disappeared. An example of a PET scan indicating the liver metastasis disappearance is included in this article (Ref.).

The scientific article where the results were published can be found here: http://www.cell.com/cancer-cell/pdf/S1535-6108(16)30087-3.pdf

What is also great about these results is that are based on Maraviroc, a drug that has already received FDA approval for treatment of HIV and has shown little side effects and toxicities even on long term treatment in humans.  https://clinicaltrials.gov/ct2/show/NCT01736813

So what we have here is a drug that alone can lead to reactivation of the immune system in some of the cancer patients and as a result tumor eradication. Until now, the idea that CCR5 blockers can reactivate the immune system and kill cancer in humans was a theory only. But with the results from Hidelberg, this is now a fact. Maraviroc is FDA approved and the side effects are limited. The drug is administrated orally. As further discussed bellow, it can be bought at online pharmacies. The only drawback is that the cost is relatively high (2000 euro /month) but if used with other drugs such as Ketoconazole, the required dose will be half (Ref.) so the cost may be around 1000 euro/month.

Note that, genetic evidence exists that links CCL5 (and thus CCR5 ) with numerous human diseases, such as liver fibrosis, coronary artery disease, multiple sclerosis, rheumatoid arthritis, asthma and atopy, atopic eczema/dermatitis syndrome, atopic dermatitis, hepatitis C virus infection, heart graft rejection and systemic lupus erythematosus (Ref.).

Update Oct 2019 – New relevant research on Maraviroc and  CCR5:

  • maraviroc: a potential effective strategy to combat breast cancer bone metastasis (Ref.)
  • Inhibition of the CCL5/CCR5 axis against the progression of Gastric Cancer (Ref.)
  • “Three additional studies targeting CCR5 for metastatic cancer have been approved by the FDA. Each study combines a drug and a biologic for CCR5+ metastatic cancer. (Ref.)
    • The first is a phase 1 study of pembrolizumab with maraviroc in patients with refractory microsatellite stable (MSS)- CRC. (Ref.)
    • The second, a phase 2 study is assessing safety and efficacy of vicriviroc in combination with pembrolizumab (MK-3475) in patients with advanced metastatic MSS-CRC. (Ref.)
    • The third is a phase 1b/2 study for CCR5+ metastatic TNBC using carboplatin and leronlimab. The study is evaluating the impact on progression-free survival (PFS) with secondary objectives to assess the overall response rate (ORR), the number of circulating tumor cells, and assess benefit based on time to new metastasis. (Ref.)”
  • Single-cell analysis revealed CCR5 governs PI3K/Akt, ribosomal biogenesis, and cell survival signaling. As CCR5 augments DNA repair and is reexpressed selectively on cancerous, but not normal breast epithelial cells, CCR5 inhibitors may enhance the tumor-specific activities of DNA damage response-based treatments, allowing a dose reduction of standard chemotherapy and radiation. Indeed, it has been found that CCR5 inhibitors enhance cancer cell killing mediated by radiation and DNA-damaging chemotherapeutic agent (Ref.)
  • Patent: Use of ccr5 antagonists alone or in combination therapy for the treatment of cancer (Ref.)

Mechanism:

Maraviroc blocks a microscopic doorway – the CCR5 receptor – which HIV uses to enter and infect human cells. This is why Maraviroc is highly relevant as an anti HIV drug.

In cancer, the relevant of CCR5 receptors is different:

The tumor microenvironment is composed of stromal and inflammatory cells that are recruited and/or locally induced to proliferate or differentiate by tumor cells or by normal cells “educated” by tumor cells. They communicate directly through cell-cell contact but also indirectly through paracrine signals predominantly constituted by cytokines and chemokines. (Ref.) Thus, chemokines, have a fundamental role not only in inflammation and immune surveillance but also in cancer progression.

CCL5, the chemokine that binds CCR5  is one of the very relevant chemokine in cancer progression, and is often detected in neoplastic tissues. Large amounts of CCL5 (that bind to CCR5 receptors) are produced by T cells present in the vicinity of tumors and it is known to be strongly associated with the tumor progression (Ref.). CCL5 plays an active role in recruiting a variety of leukocytes into inflammatory sites including T cells, macrophages, eosinophils and basophils.

CCL5/CCR5 interactions may favor tumor development in multiple ways: acting as growth factors, stimulating angiogenesis, modulating the extracellular matrix, inducing the recruitment of additional stromal and inflammatory cells, and taking part in immune evasion mechanisms. This is done via e.g. activation of IKKalpha/beta, NF-κB, Jak-STAT, MAPK/ERK signaling pathway, inducing the mTOR pathway (Ref.)

Another relevant mechanism related to CCL5/CCR5 interaction is specifically connected to the Macrophages:

Macrophages derived from monocyte precursors undergo specific differentiation depending on the local tissue environment. They respond to environmental cues within tissues such as damaged cells, activated lymphocytes, or microbial products, to differentiate into distinct functional phenotypes. The M1 macrophage phenotype is characterized by the production of high levels of pro-inflammatory cytokines, an ability to mediate resistance to pathogens, strong microbicidal properties, high production of reactive nitrogen and oxygen intermediates, and promotion of Th1 responses. In contrast, M2 macrophages are characterized by their involvement in parasite control, tissue remodeling, immune regulation, tumor promotion and efficient phagocytic activity. (Ref.)

CCL5 is bound by the chemokine receptor CCR5, which is expressed on the surface of macrophages. Antagonist of CCL5 receptors is strongly associated with a shift of  macrophage subsets to a pro-inflammatory phenotype, i.e. a shift from M2 to M1 (Ref.). Therefore, blockage of CCR5 by maraviroc is expected to lead to the reprogramming of tumor-associated macrophages, which then destroy the cancer cells, rather than promoting tumor growth.

Indeed, this is what has been observed in the recent clinical trial from Heidleberg (Ref.).

The results suggest that monocyte/macrophage subsets differentially contribute to progression and resolution of tumors and that this balance can be successfully modulated by chemokine antagonists.

Note: another drug that may be used to modulate macrophages by inhibiting M2 is Plerixafor and has been discussed earlier on this website https://www.cancertreatmentsresearch.com/?p=265

Synergies:

Statins: CCR5 receptors, are located on cholesterol-rich ‘lipid rafts’ within cell membranes. Statins may reduce lipid raft numbers, potentially altering CCR5 availability and efficacy. http://hivclinic.ca/main/drugs_interact_files/CCR5-int.pdf

Administration and Dose:

The drug administrated in the clinical trial was Maraviroc at 300mg 2x/day https://clinicaltrials.gov/ct2/show/NCT01736813

However, with Ketokonazole it has to be taken at 150mg, 2x/day https://aidsinfo.nih.gov/drugs/408/maraviroc/0/professional

Source:

Maraviroc, 60 Tabs 300mg $2147.74 http://www.buy-pharma.co/Celsentri-p-2560.html

Safety and Side Effects:

According to the clinical trials before becoming an anti HIV drug, the most common side effects reported with twice-daily treatment were cough, pyrexia, upper respiratory tract infections, rash, and dizziness. The most common side effects reported with once-daily dosing were diarrhea, edema, influenza, esophageal candidiasis, sleep disorders, rhinitis, parasomnias, and urinary abnormalities. Nausea, diarrhea, fatigue, and headache were common in Phase 2b/3 trials. (Ref.) Maraviroc may also cause severe liver symptoms.

More about side effects can also be found here http://www.rxlist.com/selzentry-side-effects-drug-center.htm

In contrast to this long list of potential side effects, the Heidelberg trial did not encounter any major issue as suggested by this statement: “The data show that the HIV medication is very well-tolerated” (Ref.)

References:

Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients http://www.cell.com/cancer-cell/pdf/S1535-6108(16)30087-3.pdf

The immune response influences the clinical course of colorectal cancer (CRC). Analyzing the invasive margin of human CRC liver metastases, we identified a mechanism of immune cell exploitation by tumor cells. While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5. CCR5 blockade in patient-derived functional in vitro organotypic culture models showed a macrophage repolarization with anti-tumoral effects. These anti-tumoral effects were then confirmed in a phase I trial with a CCR5 antagonist in patients with liver metastases of advanced refractory CRC. Mitigation of tumor-promoting inflammation within the tumor tissue and objective tumor responses in CRC were observed.

Anibamine, a Natural Product CCR5 Antagonist, as a Novel Lead for the Development of Anti Prostate Cancer Agents http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914538/

Accumulating evidence indicates that the chemokine receptor CCR5 and the chemokine CCL5 may be involved in the proliferation and metastasis of prostate cancer. Consequently, chemokine receptor CCR5 antagonists could potentially act as anti prostate cancer agents. As the first natural product CCR5 antagonist, anibamine provides a novel chemical structural skeleton compared with other known antagonists identified through high-throughput screening. Our studies demonstrate that anibamine produces significant inhibition of prostate cancer cell proliferation at micromolar to submicromolar concentrations as well as suppressing adhesion and invasion of the highly metastatic M12 prostate cancer cell line. Preliminary in vivo studies indicate that anibamine also inhibits prostate tumor growth in mice. These findings indicate that anibamine may prove to be a novel lead compound for the development of prostate cancer therapeutic agents.

The Inflammatory Chemokine CCL5 and Cancer Progression http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910068/

Until recently, inflammatory chemokines were viewed mainly as indispensable “gate keepers” of immunity and inflammation. However, updated research indicates that cancer cells subvert the normal chemokine system and these molecules and their receptors become important constituents of the tumor microenvironment with very different ways to exert tumor-promoting roles. The CCR5 and the CCL5 ligand have been detected in some hematological malignancies, lymphomas, and a great number of solid tumors, but extensive studies on the role of the CCL5/CCR axis were performed only in a limited number of cancers. This review summarizes updated information on the role of CCL5 and its receptor CCR5 in cancer cell proliferation, metastasis, and the formation of an immunosuppressive microenvironment and highlights the development of newer therapeutic strategies aimed to inhibit the binding of CCL5 to CCR5, to inhibit CCL5 secretion, or to inhibit the interactions among tumor cells and the microenvironment leading to CCL5 secretion.

CCR5 Antagonist Blocks Metastasis of Basal Breast Cancer Cells http://cancerres.aacrjournals.org/content/72/15/3839

The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer progression remain unclear. Here, we conducted microarray analysis on 2,254 human breast cancer specimens and found increased expression of CCL5 and its receptor CCR5, but not CCR3, in the basal and HER-2 genetic subtypes. The subpopulation of human breast cancer cell lines found to express CCR5 displayed a functional response to CCL5. In addition, oncogene transformation induced CCR5 expression, and the subpopulation of cells that expressed functional CCR5 also displayed increased invasiveness. The CCR5 antagonists maraviroc or vicriviroc, developed to block CCR5 HIV coreceptor function, reduced in vitro invasion of basal breast cancer cells without affecting cell proliferation or viability, and maraviroc decreased pulmonary metastasis in a preclinical mouse model of breast cancer. Taken together, our findings provide evidence for the key role of CCL5/CCR5 in the invasiveness of basal breast cancer cells and suggest that CCR5 antagonists may be used as an adjuvant therapy to reduce the risk of metastasis in patients with the basal breast cancer subtype.

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases http://clintransmed.springeropen.com/articles/10.1186/s40169-015-0047-4

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations.

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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69 thoughts on “Maraviroc: An anti-HIV Drug that Reactivates the Immune System to Fight Cancer

  1. After searching for info on maraviroc, it seems the tumor and metastasis reduction is due not only to immunostimulation, but more due to suppression of cancer associated fibroblasts.
    Blockade of the chemokine receptor, CCR5, reduces the growth of orthotopically injected colon cancer cells via limiting cancer-associated fibroblast accumulation.
    http://www.ncbi.nlm.nih.gov/pubmed/27340784

    Also found something more interesting – a cytotoxicty of 78% by a combination of temozolomide + ritonavir + aprepitant, against a glioma cell line.
    “We conclude that a remarkable synergy exists between aprepitant and ritonavir”, which may apply not only to glioma cells. This was also proposed part of the CUSP9* protocol.
    Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells.
    http://www.ncbi.nlm.nih.gov/pubmed/26603162
    In combination with the previously tested temozolomide + macitentan (remarkable results), this could become a new standard for glioma treatment.

    1. Thanks Ovidiu. Indeed, the anti cancer effects of Maraviroc are twofold: on one hand immunostimulant due to shift of M2 to M1 and on the other hand inhibiting the rebound of tumors supported by the existence of M2 (i.e. M2 inhibition) which is known to have strong impact on the whole tumor micro environment including fibroblasts as you referenced. Plerixafor, was inhibiting M2 only leading to strong anti cancer effects specifically in combination with chemo. In that case, chemo would kill tumors cells while Plerixafor would inhibit the repair of the damage which would be initiated by M2. Now what we see is that Maraviroc has two effects in one from a Macrophages point of view.
      Off course, the events are more complex, but this is trying to make things simple.

  2. Hi Daniel

    today results about my mother
    the tumor markers climbed to 938 !!!
    it was 450 just before 4 weeks !!?
    the Scan showed that nearly every thing is stable like before 3 months , but also there is a very very little new spots on the liver

    note : there is a big spot on the liver that are still stable for months , the size of it is 2.5cm , this is the biggest spot in the body

    —————
    our protocol the past 4 weeks was the same as before , except :-
    we run out of DCA the past 2 weeks , but we also added Baicalien (Scute) 5g daily , Mebendazol 600mg daily , and increased the dose of artemisia annua to 10g daily …
    ————-
    another thing , my mother can’t stand easily on her legs due to the neuropathy , its not caused by the DCA it self , but also by the chemo
    ———–
    at last , i have a little question about the liver mets : with this size (2.5cm spot + very little spots) , would it considered a problem ? if not : when it will be a problem ?

    thank you so much

    1. Emad, based on all what you wrote before sounds like DCA is essential. So why would you run out of it …
      For the liver spots I would go for TACE at prof Vogl in Frankfurt if you can afford. The drug discussed above may also be relevant.

      1. Thank you so much Daniel

        yes DCA is essential , but the neuropathy became worse

        even more I think that DCA is more more effective than chemo with my mother , I’m planning to try it alone and see the results

        and maybe I will try to prepare my first DCA IV , I don’t need that kolliphor thing to Solubilize it 😀

        anyway , I’m trying to find Maraviroc here in our country , i want to give it a shot especially for liver mets

        prof Vogl will be our plan Z

        we still have more options for now , thanks to Jose and thanks to you 🙂

  3. Good article, very promising, as not so often can we have a good clinical trial outcome for a drug, which exists already.

    Question 1 – would it be good to use it together with gcmaf? to make macrophages more potent?
    Question 2 – how long treatment should be, I read something about 8 weeks…
    Question 3 – toxicity to liver, we are fighting to make liver again functional after complication after Sirt.

    1. Hello Ann, my husband had the same problem after Sirt just like your husband. Did you do anything to help the liver recovers.
      I am so worried, my husband has no energy and starts getting jaundice. I gave him milk thistle, quercetin, lemongrass tea. Did you try maraviroc or Koch therapy (MG)? Artemisinin treatments reduces his pain a lot but I’m afraid the lost of energy means the cancer is growing.
      I was looking into cancer ablation (image guided). However, I just read about a young woman died when she was undergone that treatment and they operate out of Mexico. Her medical bill went up to 600K. To find something that works for this disease is so hard.
      Any one with experience on liver mets please chime in.
      Thank you.

      1. Hi Hanh, I will let Ann know you wrote a msg to her. I also just installed a plugin so that users can receive a notification when someone writes a reply to their comments.
        Can you please let me know what is that place where the patient had to pay 600k? Regardless of the clinic I would not go there.
        Image guided ablation in Europe is much much cheaper. Can you please add here the link with the report about that young patient if you still have that?
        Regarding the outcome of the young patient after ablation, I do not think that is a typical outcome from ablation. But I think that every step we take in (serious) cancer treatments involves risks. We need to balance these risks with the risk of not doing anything.

  4. Hi Ann,

    1. In a pharst phase I would not add anything else that may interfere with Macroph. Instead I would combine this drug with effective treatments e.g. salinomycin, 3BP, chemo, diflunisal, etc.
    2. I read it like this: until complete remission or sign of progression
    3. I would contact the Heidelberg group and ask them what they would suggest giving your husband liver state. I expect they are experts since they treated exactly patients with liver mets.

  5. Daniel.
    Ad 1. We intend to make TACE with prof Vogl next week if parameters are good enough to proceed. But there is just small issue that we would not know if Maraviroc works or not, I mean is result of TACE or not. But ok I understand your point that the most important is that sth works (unfortunately we have to watch expenses ?).

      1. I didn’t noticed ! 🙂

        TACE alone did shrink our tumors, but they returned after time. TACE do not eliminate tumor , it make them shrink, make inactive for some time ( for us it was 4 months) but then they regrow if you do not do something.
        With immunotherapy I hope that smart macrophages will eat tumors to the last small cell so nothing will regrow 🙂

        So my point was, if we do TACE and in the same time we use Maraviroc we will not know what works exactly, did you get my point.
        I like prof Vogl, a lot, but he still cannot give us cure which I search so hard ( with your so precious help) 🙂

  6. Hi Emad, did you start on MG? i thought that was a part of your plan..
    also, Dear D, are you aware of the cost of the treatment at Heidelberg? are they still using Salinomycin too?
    thanks in advance.

    1. Thy are still using Sal but not sure about the price – based on the info I have should be in the range of 10k euro with Chemo. If that sounds accessible contact them and check the exact price for the number of cycles they suggest.

    2. Hi pouya

      no we didn’t receive MG yet , but its a matter of time until we get it , and sure I will always share our results for all of you

      and also we will receive Salinomycin , and I will add 3-BP and Diflunisal after that so I will have a more options in case some of them didn’t work

      but my hope is that MG will work and do the job 🙂

      my best wishes for you

    1. when I find the time I will write a post on DCA. for now, here is how some German clinics are doing it:
      – dose min 1.5g/day/IV, 2-3x/week
      – dose max I have seen clinics administrating even 4g/day/IV, 2-3x/week
      – usually the dose depends on the weight and for IV may go from about 30mg/kg even up to 70mg/kg a few doses/week(for oral the daily dose is about 20mg/kg with pause e.g. in the weekend)
      – preparation method same as 3BP (see the post on 3BP), from powder, sterilized with 0.2 syringe filter
      – administration in 250 to 500ml NaCl during one hour
      That is what they are usually doing and I think Medicor clinic too.

  7. hi daniel

    thank you for your reply.

    i ll order the dca this week and try it.

    For the same purpose,do you have a method for preparing iv curcumin but without kolliphor?

    i ve read that your two methods ,and both are with kolliphor.

    thanks again

  8. hi daniel

    thanks for the reply

    but if we start from the extract already,how do we do the iv sol?

    in the meantime,do you have any provider of the iv solution without kolliphor as the one i have contacted in germany said i have to come there if i want to buy from them (they do not ship)

  9. hi daniel

    i m in location where i can t do this in a clinic,

    we can have a nurse who can prepare all this if i can get the instructions and process to do it

    thanks

  10. hi daniel

    how come?

    don t you see the email adress?

    i m using the same since 2/3 years and there is nothing to hide beside protecting everyone privacy

  11. Hi Daniel, if we can raise fund, which clinic do you think have the best promising protocol. Before we were thinking Dayspring with 3-bp but that is not an option anymore. My husband developed ascites, no energy and has abdomen pain most of the time but his oncologist keeps insist on using 5-fu and avastin while his tumor marker still going up. We use tagamet, metformin, curcumin, artemisinin & artesunate, I recently added cyproheptadin, quercetin but I think we needed to do more than that. He has terrible abdomen pain when I added mebendazole so I stop. Is this Maraviroc
    medication something we can do it ourselves. His liver is in bad shape after SIRT. If I am the patient it would be much easier but since it is my husband’s life I am so scared of making mistake. I would appreciate every one experience.
    Thank you.

    1. Hi Hanh, sorry I didn’t see your post.
      That is exactly the same situation like we had. After SIRT first everything was ok, then two months after, markers and liver enzymes started to raise. As we already did è ablation at prof Vogl, our oncologist put fault on all these treatments , that my husband liver is full of scars. But for me all the symptoms were relared to radiation hepatitis.
      My husband also developed jaundice, bilirubin was 5, not any treatment could be added.
      Very important step in recovering ( now bilirubin is 2,5 still to high but now we are under folfiri which is metabolizedd by liver )was adding cortison ( we used Medrol quite high dose of 50 mg) it took oone month of cortison to calm inflammation) Liver cannot regenrate if inflammated. Little by little it started to get better, but very slowly and honestly they were moments were I thought we will not make it. I stopped all the treatments, I gave only milk thistle – 210 mg per day , Essentiale forte and Hepa merz and also Alpha lipoic acid). but I think it was cortison which made it worked. it was idea of prof Vogl to add it and luckily our oncologist agreed to give it to us There was also a blood clot in liver so injection Clexane was added. it is important that they make MRI to see if there is not a blood clot in liver of your husband because it can make liver stop working.
      I am sorry for a mess in my message, but I am very tired but I would like to help you. Can you tell me your last liver enzymes, CRP etc. I think you should insist on cortisone this should make bilirubine falling down. Do not think now about ablation or any other hard treatment, let liver first recover. I know it is hard, but looks the best solution.
      I contacted prof from Heidelberg and he told us the same, we have to wait liver works beter.
      Now we are dealing with withdrawal of cortisone, we were not sure if liver will start to work without cortisone, we are dealing with general inflammation now, but liver seems to improve slowly. Long term cortisone ike we had made our husband very sick, small viruses made big damage to his organism, but as I told it was I think the only way.
      I am not sure it is already fixed but it is better than it was.
      if you have any question, let me know.

  12. Hi Hanh, sorry I didn’t see your post.
    That is exactly the same situation like we had. After SIRT first everything was ok, then two months after, markers and liver enzymes started to raise. As we already did è ablation at prof Vogl, our oncologist put fault on all these treatments , that my husband liver is full of scars. But for me all the symptoms were relared to radiation hepatitis.
    My husband also developed jaundice, bilirubin was 5, not any treatment could be added.
    Very important step in recovering ( now bilirubin is 2,5 still to high but now we are under folfiri which is metabolizedd by liver )was adding cortison ( we used Medrol quite high dose of 50 mg) it took oone month of cortison to calm inflammation) Liver cannot regenrate if inflammated. Little by little it started to get better, but very slowly and honestly they were moments were I thought we will not make it. I stopped all the treatments, I gave only milk thistle – 210 mg per day , Essentiale forte and Hepa merz and also Alpha lipoic acid). but I think it was cortison which made it worked. it was idea of prof Vogl to add it and luckily our oncologist agreed to give it to us There was also a blood clot in liver so injection Clexane was added. it is important that they make MRI to see if there is not a blood clot in liver of your husband because it can make liver stop working.
    I am sorry for a mess in my message, but I am very tired but I would like to help you. Can you tell me your last liver enzymes, CRP etc. I think you should insist on cortisone this should make bilirubine falling down. Do not think now about ablation or any other hard treatment, let liver first recover. I know it is hard, but looks the best solution.
    I contacted prof from Heidelberg and he told us the same, we have to wait liver works beter.
    Now we are dealing with withdrawal of cortisone, we were not sure if liver will start to work without cortisone, we are dealing with general inflammation now, but liver seems to improve slowly. Long term cortisone ike we had made our husband very sick, small viruses made big damage to his organism, but as I told it was I think the only way.
    I am not sure it is already fixed but it is better than it was.
    if you have any question, let me know.

  13. One more thing, I saw you were using just like we did metformin. If I were you Iwould also stop it, it is very toxic for liver, specially for the liver damaged byt SIRT. I will again add metformin when liver will fully recuperate ( means all enzymes within normes) but I will carefully check enzymes after adding metformin.

    1. Hi Ann, thank you for your reply. After reading your reply I asked his doctor for dexamethasone and my husband has been taking it for the last 3 days. I can tell he looks less jaundice, his urine is lighter (before it was so dark almost like brownish, sign of liver not functioning), he can eat a little bit better. I feel like there is hope again. Thank you for taking time to let me know how to reduce liver inflammation.
      Did you try Gelum drop? My husband wears a mouth guard at night. In the morning I can smell acid from the piece. After using Gelum Drop (thank to Daniel) for the last 3 days I do not smell acid any more. Hopefully, it does reduce acidity around the tumor thus slow or reverse tumor progression or at least help medications get to the tumor.

      Hope for good news for all of us.
      Hanh

      1. It is good news Hanh.
        Have you maybe idea how to get rid of ascites? We are ready to go to Heidelberg, but as long as we have ascites, no biopsy.
        For gelum drops, there is one thing which make me thinking of it is so good. It contains iron, and iron is not good to supplement when we have cancer. Does anyone has here opinion?

        1. Hi Ann, my husband’s heart rate had been consistently above 100 for the last 10 months. For the last few days his heart rate has been down to 80s and sometimes even 70s. Maybe Gelum drop does what it claims it does, oxygenate and remove acid lactic. I think both are good. For ascites the liver has to work to produce albumin so the leaking fluid will be stop. I just found some home remedy for removing the fluid. One is to take garlic juice 3 times a day, bitter gourd juice, celery juice. I have no way to see the effect on the abdomen fluid but his leg’s fluid retention has been reduced.
          What treatment is your husband going to have at Heidelberg and what is the cost involved if you dont mind sharing. Right now my husband’s situation is improved a bit but I don’t know for how long so I would like to explore other plans.
          Your husband has good doctors, my husband’s doctors did not address his liver inflammation after Y90 nor check for blood clot. I still don’t know how to ask them to check for that. Every thing they would contribute to disease’s progression and just chemo if we want treatment. What is your husband’s symptom for blood clot in the liver?
          Is your husband’s bilirubin still high? I think sun bathing will be good to help break down bilirubin, my husband does it 30 minutes every day.
          Take care.

          1. hi Hanh,

            There can be so many reasons for ascites that it is difficult to say what is the problem. I ordered gelum drops, we will see, I hope they will have a good effect.
            For the treatment in Heidelberg I will know something more in few weeks, when we see profesor. It will be probably some mix of Maraviroc and immunotherpay drugs, but it depends the biopsy of tumor. I would like to have a biopsy with immunoprofiling, but I am not sure if they will take biopsy due to ascites. We will see and I will describe everything here.
            We started from bilirubin 5 now it was one week ago 2,5.
            The blood clot was visible on CT, I asked for CT because I thought that jaundice is effect os stone blocking duct in liver, but they found a blood clot. All these research was due to jaundice.

            Take care, as soon I know sth more I will write it. Thanks

  14. For us probably reason for ascites were tumors in de belly. We have just receive scans results and it is not only now in the liver but also in the belly and it is possible that these tumors produce liquid.
    I expected something beter than that. We will switch to Erbitux now, ans Heidelberg has to wait for some time.

  15. A small update on Maraviroc plus Erbitux.
    I am afraid I do not have good news. CEA rised from 120 to 280, what can be rather bad sign.
    I will know more after scans and I will update.

  16. Yes, he had flu. He had crp 170 now it is 15 after week of antibiotic.
    I can understand small rise of cea but from 120 to 280?
    I am sorry I do not write too much, I have chronic insomnia for the moment, have just not enough power.
    Take care guys!

  17. Hi everyone!
    So we had scans today.
    It wasn’t good, all the tumors grew back.

    So I can state that maraviroc plus Erbitux is surely not a good mix.
    We stopped maraviroc temporairly, we will be now on erbitux plus irrinotecan alone.
    I will report !

    For everyone fighting, good luck. I keep my fingers crossed for you !

    1. Hi Ann,

      I am sorry to hear there is progression. Have you used any of the tips on improving chemo effectiveness?
      Where did you get Maraviroc? From Heidelberg (German National Cancer Center)?
      Thank you for the update.

      Kind regards,
      Daniel

  18. Thank you Daniel for your nice words
    Yes, we used some of tips- natural like omega 3, honokiol -we have to be carefull due to liver issue. I will come back to read once again ,maybe will get new inspiration.

    Yes, maraviroc (celsentri ) from was Heidelberg.
    We will be there again to look for some other options.

  19. Hi Daniel,

    I knew this name, Mebendazole was familiar from somewhere. Apparently, from the news. After it proved to be effective against cancer, the company that acquired the exclusive rights to it, increased the price for a single dose from a dollar or so to more than 700 dollars! For a drug that has been in use for 40-50 years against worms! Insane. See this: http://www.news4jax.com/consumer/pinworm-prescription-jumps-from-3-to-up-to-600-a-pill This is for Ergin: https://www.mesotheliomahelp.org/2017/02/mesothelioma-patients-may-someday-use-pinworm-drug-treat-asbestos-cancer-30255/

    Here is the story about the price increase: http://moneyweek.com/the-pharma-price-gouging-scandal/ They called Martin Shkreli, the man behind this abomination “the most hated man” in America. Thanks God, people can order it in the US from abroad.

    1. Hi Helga,

      Mebendazole is one of the drugs I like the most. It has huge potential: clear science behind its anti cancer action, case reports published with serious anti cancer results, it is low cost (still in most countries) and it is easily accessible + little to no side effects. It is one of my preferred anti cancer drugs.
      My reaction to your post is WOW!!! I did not know they were increasing the cots in USA. Those costs cannot be explained in anyway given that you can buy it from Alibaba at maybe 200USD for one kg powder. There are some things that are clearly wrong in this world if a drug company is allowed to do something like this …

      Kind regards,
      Daniel

  20. My mother has colon cancer ( doctor removed 16 cm with the tumor) with extensive liver metastases. I wished I found this site sooner, as now, 2 month after the surgery and one near death experience with CAPOX I am afraid it is too late. The Cave and Porta vain were partially blocked by tumor end May, before surgery, and we have not done a second CT yet. She is not mobile, she has not left the bed for 3 weeks now. She cannot eat, so we started Kabiven to help her recover after stopping the CAPOX protocol.

    We have started today with Vermox, but I am afraid it is too little and too late. Has anyone combined Vermox with Maraviroc? I am affraid of liver toxicity, as she does not have a lot of liver left. Since Saturday she shows signs of ascites, so we don’t have a lot of time left.

  21. Hi Daniel

    I am located in Romania.

    Short update on my mother condition: after almost 2 month with Vermox ( Mebendazole) she had a second CT scan, and it showed 0.5 cm tumor growth on 2 of the 3 axes. So we stopped the Vermox, and started the Maraviroc, with half of the dosage of the trial, as she was too weak.
    She has supported the drog very well, and the edema of her legs reduced very much in the first week, so now she is mobile again. She can walk on small distance, but still need help and supervision for stairs, small obstacles etc.
    We have consulted 3 other doctors ( oncologists) but they refused to prescribe her any more chemotherapy. They told her to take Avemar, Cucurmin ( 2/day) and Salvestrol Platinum ( 2/day), together with Sylimarin (3/day).

    She will complete 1 month with Maraviroc in 5 days, and we plan to increase the dosage to the trial one.

    I’ll post more updates after the next scan ( we plan an MRI scan) probably after 2 month of Maraviroc.

    Best regards,
    Monica

    1. Hi Monica,

      Thanks a lot for the update! This is a very valuable report! The reduction of edema is a very good sign!
      Please keep us up to date and as also discussed by e-mail, if I can help with anything please let me know.

      Kind regards,
      Daniel

    2. Hi Monica,

      After studying my case, one drug that interests me is maraviroc. I’m from Spain so my only reference to buy is this blog(Daniels link doesn’t stork) . Can I ask you how should I proceed to buy it?

      Do you know if Maraviroc can be taken when you are going taken some chemo? I wish very good results in your following tests?

      Kind regards

      Inaki

  22. Hi Inabari

    Maraviroc is a prescription drug. I don’t know if it’s approved for usage in Spain. We got it in pharmacy, based on a doctor prescription, but I don’t know how is the regulation in Spain. It’s best if you speak to your doctor, and show him/her the study – there is a link in this article.

    The doctors have refused to give my mother any more chemo, after the extreme bad reaction she had at CAPOX. But the study said the chemo after 2 moth of Maraviroc alone had better result even on the cases previously resistant to chemo. So you should follow the standard treatment for Spain, and use Maraviroc if the chemo is no longer effective. I have not found any reference of Maraviroc taken together with chemo, but your doctor my contact the study coordinator to consult on this.

    I will post an update as soon as my mother has the MRI. She still believes the doctors can help her, and tolerates Maraviroc while no other option is available.

    Best regards,

    Monica

  23. I’ve just noticed that this year medicine Nobel price has been awarded for cancer research, especially in PD1 inhibitors and CTLA -4 ‘s protein receptor ( CCR5 https://en.wikipedia.org/wiki/CCL5, https://en.wikipedia.org/wiki/CCL4 ) blockage:
    https://www.nobelprize.org/prizes/medicine/2018/press-release/

    I believe the Maraviroc action is exactly in this area, and the continuation of Maracon trial (mentioned in the above article) is continued by Piccasso trial https://clinicaltrials.gov/ct2/show/NCT03274804 which is adding the PD1 inhibitor Pembrolizumab in the mix.
    This trial is still open, and it’s dedicated to Refractory Microsatellite Stable mCRC (metastasized colon cancer) .

    Ps. I am not a doctor, so I apologies if I wrote anything inaccurate. This post shows only my understanding of this subject, and you should read the referenced materials in order to have a better understanding.

  24. Hi

    Getting a CT scan in Romania is not easy. My mother had a CT on 3 segments (chest, abdomen and pelvis) last week and we got the interpretation today.

    In short, after 3 month of Maraviroc ( 1 month 150 mg twice/day and 2 months of 300 mg twice /day) + Cucurmin, Salvelstols, Avemar Sylimarin, + some vitamins, the biggest metastasis showed a small decrease on one axe from 120 mm to 111 mm, but the second biggest metastasis has increased with 1 cm . Also, there is 6mm nodule in the lungs.

    For the first time she got some tumor markers done: CA125 43.8 ( it should be below 35) and CEA 56.8 ( should be below 3)

    The oncologist she visit in Brasov, told her she has waited too long to get back on chemo, and asked her to start right away FOLFIRI, 3 days, with 2 week pause in between .

    She was scheduled to start last yesterday, but on Saturday she got a cold, and since then we are fighting with the temperature of 38.4 . Today she feel better, so hopefully she will be fit for chemo next week.

    Hopefully the chemo will work better after Maraviroc. We have stopped it 2 weeks ago, and the oncologist form Brasov advised us against taking it together or in between chemo .

    Best regards,

    Monica

    1. Hi Monica,

      Thank you for the update!
      Could you please let us know how would you compare the tumor evolution prior to Maraviroc vs. that after starting Maraviroc? Do you think Maraviroc slowed down the tumor, or there was no added value so far for your mom?
      Thank you.

      Kind regards,
      Daniel

  25. Hi Daniel

    Personally I think Maraviroc helped. But my family points out that while there is a little shrinkage in the biggest tumor ( 14/12 cm at first CT, then 14.5/12cm on second CT – after Mebendazole – and 14.5/11.1 cm at this last CT), the second biggest tumor in the liver increased for 2.2 cm first CT to 2.8cm at second CT and 3.6 cm at this last CT. Also she has a very small nodule in the lungs.

    What I can say is that it has not done any harm, the doctor was surprised with the liver blood work. So as long as the liver can function, there is still hope.

    For me the most interesting part of the test was about the 6 or 7 patients that went back on chemo after Maraviroc, and got their best results with Folfox and Folfiri + avastin . So I really hope she will react better to the chemo, as the 2 sessions of CAPOx she got before the coma did not seem to have any positive effect on the tumor.

    So I’ll post again after the next CT, and maybe Maraviroc can help patients resistant to chemo .

    Best regards,

    Monica

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