Saturday, 22 September 2018

Medications and supplements during treatment !

Hi All

My mother was diagnosed about a month and a half ago with GBM the surgery was performed and the tumor was completely removed ,now she treated TMZ and Radiation

I purchased supplements that were taken before starting chemotherapy and radiation, such as resveratrol, green tea, mushrooms, pozzalia, turmeric, omega-3, flaxseed oil, melatonin, broccoli sprouts etc
But  we stopped it during treatment, is it better to stop eating supplements during treatment or take it during treatment??

What do you suggest to take medicines and supplements during (and after) chemotherapy and radiotherapy??
My mother is 49 years old and has no other health problems at all

Thanks in advance



  1. Hi Muddar,
    When did she start her radiation treatment?

    There has been quite a bit of discussion on the blog recently about cocktails for during radiation, so it might be helpful to start by reading those posts and their comments.

  2. Is she taking any anti-seizure medication? There was a single arm trial testing Depakote (valproic acid) in combination with radiation, with good survival outcomes for newly diagnosed GBM.

  3. In fact i dont know ,She is taking
    Radiation 6 weeks started from Tuesday 5 days weekly
    TMZ 120 mg Daily Including weekend for 6 weeks started from tuesday
    ZOFERAN Before 1 hour of TMZ , is there any problem if she take it before 1 hour before TMZ?

    METHYLCOBALAMINE 3 times daily
    PHENYTOIN two times daily 100mg
    FRUSEMIDE 2 times 20mg
    ESOMEPRAZOLE 1 time daily morning before eating

    Can we start go with Depakote (valproic acid)?

    1. Which country is this? Phenytoin is an anti-seizure medication, but not much used for brain tumor patients in North America at least. Most common here is levetiracetam (Keppra), and previously Depakote was common. In addition to anti-seizure activity, Depakote may have radiosensitizing activity, probably dose-dependently, and Keppra may have chemosensitizing activity. Phenytoin hasn't been shown to have potential anti-tumor activity, so if possible you try to switch over to Depakote or some other valproic acid equivalent during radiation. Under doctor supervision would be best.

    2. Thanks a lot for quick reply
      We are in Dubai (UAE),Ok i will ask doctor tomorrow to switch over to Depakote, Can you tell me how many mg she have to take daily ??

      Her weight 63 kg Height 158 cm..

      I see this but i don't understand how many mg she have to take daily

      Waiting your kind reply Stephan

    3. The outcomes of this trial were published in full in 2015.

      Valproic acid treatment started 1 week before the start of radiation at a dose of 10-15 mg per kilogram of body weight per day, and increased to 25 mg/kg per day by the first day of radiation.

      10 or 15 mg per kg for someone who weighs 63 kg, would be ~625 or 1000 mg daily (Depakote typically comes in 500, 250 or 125 mg tablets). And then it was escalated up to 25 mg/kg per day by the start of radiation, or 1500 mg daily for someone of your mom's weight.

      The daily doses were divided into two doses per day. So instead of 1500 mg all at once, it would be 750 mg twice daily.

      I also summarized this trial on my article here:

    4. This wasn't a randomized trial but outcomes are very favorable compared to historical controls. 38% were progression-free at 18 months from the start of radiation. Median survival was 29.6 months from the same star point, and 56% survived to 2 years. I doubt there will be a phase 3 trial to confirm these outcomes because a large retrospective study claimed there was no increased survival in patients who taking Depakote for anti-seizure purposes during standard treatment of newly diagnosed GBM. The problem with that study is that it wasn't controlled for dose - it was *any use* versus *no use* of valproic acid. I tend to think the higher doses as used in the phase 2 trial are necessary for more consistent anti-tumor effect, though this can't be or hasn't been proven.

    5. Thanks a lot
      so we have to start 25mg per kilogram ? cause we start the radiation?


    6. I would still probably start at the lower dose and increase over the course of a week. There's a reason they started at the lower dose, because some people might not tolerate the higher doses that well, and it's usually a good idea not to jump in and start a drug at a high dose immediately.

    7. Apart from valproic acid I discuss some other ideas for helping radiation be more effective, on the radiation page. Some of this is based on clinical evidence and some is based only on preclinical (rodent) evidence.

    8. Also how long time she can use Depakote ?
      when we stop the the medicine ?


    9. In the phase 2 clinical trial the Depakote was continued until the end of radiation. Has your mother's tumor been tested for MGMT status? MGMT promoter methylated or unmethylated? It should say on the pathology report if so.

    10. I read it

      I think we can combine Resveratrol,celebrex and Depakote During Chemoradiation to have good result

      what is your opinion Stephan?

    11. I will have MGMT Status on Monday or Tuesday

    12. I feel there is a good evidence for a COX-2 inhibitor such as Celebrex to prevent the increase of PGE2 production in the tumor that happens in response to radiation. Doctors often don't want to combine anti-inflammatory drugs with dexamethasone for fear of gastrointestinal side-effects, but this is likely more of a problem with non-specific COX inhibitors such as ibuprofen, aspirin, etc.

      Ideally she would be able to lower the dose of dexamethasone as much as possible.

      "Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts."

      "In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy."

      Celebrex might also help reduce cerebral edema, which is the main reason brain tumor patients need to take dexamethasone.

    13. Dear Stephan thanks for your reply
      We see doctor today and he told us it is better to reduce amount of Decadron so we make it 2 mlg today and we are doing to stop it in the end of week or before ..

      I asked him about Celebrex and he say there is no problem to take it ..
      For Valproic acid he said I cant tell to use it or not,It is up to you cause maybe reduce the effect of Temodal..
      I read about Chloroquine Phosphate, 250mg/day from Rich cocktail and i want to ask you if we can merge three drugs.Celebrex,Valproic acid and
      Chloroquine Phosphate..

      Thanks a lot

    14. I haven't heard of any problems combining that trio of drugs.

  4. I think Phenytoin is similar to Depakote(valproic acid) ?? Right

    1. No, the thing they have in common is that they're both anti-seizure drugs, but beyond that they're not similar.

  5. To your question on whether or not to take supplements / meds during radiotherapy phase or not, I would personally suggest to do it - just pick right and go with the ones that have the best evidence for that phase. It's the time when you have the most concurrent standard treatments (RT + TMZ) going on, so I think it would be a shame not to build on this for some additional synergy and extra-efficacy. One thing you could also consider is a Ketogenic diet, which has some astonishing animal model evidence for it during the radiotherapy phase. See this like for some general infos on this phase in the treatment:

    BTW, doctors are highly likely to advise against this as they generally do not want to interfere with standard care in any way. So this is something you might be a bit on your own with.

    Best of luck with the treatments!

  6. Thank you for your reply John
    I am currently thinking in use three drugs,Celebrex,Valproic acid andChloroquine Phosphate during the six-week period.

    And then use supplements heavily after six weeks

    What do you suggest?

    1. It's a difficult question. From my perspective, supplements can serve a couple of key purposes during radiation, namely to 1. protect the healthy brain tissue from radiation damage and 2. to act as a radiosensitizer and enhance treatment efficacy.

      Most doctors will advise against the use of supplements and especially the use of antioxidants during the radiotherapy stage, because they fear that there is not enough evidence to prove that supplement use is safe and will not interfere with treatment efficacy. In my opinion, they miss the point a bit on GBM, though, since their golden Standard of Care treatments (chemoradiation) are not even a cure for the disease, but rather only offer a possible life extension... So I really think they go a bit overboard being scared something might possibly interfere with their treatments, which are not even really effective in the first place. On the other hand, there is a lot of evidence out there that certain supplements actually enhance the efficacy of radiotherapy & chemotherapy quite a bit, e.g. Curcumin, EGCG, Resveratrol, Sulforaphane, Genistein, Pterostilbene, ...

      A good read in respect to this decision is this piece by Ben Williams, author of 'Surviving Terminal Cancer':

      Ultimately, it's a trade-off you will have to decide yourself. In my case, I went pretty heavy on supplements during the RT phase and I think I would personally do it again this way.


    2. Thank you for that insight. My husband is only two weeks into treatment and the doctors are pushing back very hard about the supplements we want to pursue. As the spouse I'm finding it very difficult to weight risk and reward when the doctors are so cautious. Are there some supplements that are more important for unmethylated MGMT? We think we want to start Metformin and Valcyte shortly against dr advice. Thanks.

    3. Hi Lori,

      It might be best to get Stephen's comment in this regard perhaps, as I lack the background to really comment credibly on specific supplements and meds. But you can find some discussion on this topic when searching the Blog with the MGMT_inhibition tag:

      Basically, there seem to be some agents that might lower MGMT expression, e.g. Antabuse (disulfiram), Keppra (levetiracetam), Prozac (fluoxetine)... but again, I'm not sure what the latest is in this regard.

      My GBM is also unmethylated, and I took Antabuse during radiotherapy for this purpose. However, I did experience some side effects after a while combining this with Chloroquine - specifically peripheral neuropathy. My Radiotherapy cocktail can be found here:

      And you can also search the blog using the cocktails tags on the right, to get other examples. I think some components are almost unanimous here during RT phase, including meds like Chloroquine, Celebrex and supplements like Omega 3 fish oil, Curcuma (Longvida), Melatonin (high dose), PSP/PSK mushroom (i.e. turkeytail extract... used for immune system boost. In similar fashion you could consider Reishii and Maitake D-Fraction), Green Tea extract, Probiotics...

      You can get some ideas here:

      There is definitely a risk-tradeoff here to consider. But again, I think it bears repeating that the existing standard of care treatments are completely insufficient to warrant anyone blindly going with the doctor's advice, which almost unanimously is to omit any kind of supplementary treatments or off-label drugs. In my opinion you get the best fighting chance when you start as early as possible to support your treatment beyond the realm of standard of care... In my case, I was lucky enough to find a neuro-oncologist open to supplement use, but this is really very rare and it's only because I specifically searched for this profile.

      Good luck with the cocktail!

    4. I just want to add a link to the following story, which very much impacted me when I first saw it. I thought it's quite a big motivator to push back on doctors' often somewhat (or very) narrow minded approach to dealing with GBM:

    5. I also forgot to add Boswellia above... I think this is a very good supplement to use during Radiotherapy, because it helps to control edema (and therefore helps limit or eliminate the need for cortisone, which has been shown to be quite detrimental)

  7. Dear John

    Thanks for you reply

    She continued using Supplements ..

    Also I sent Email to Ben and he replied to me to take lipitor, metformin, doxycycline, and mebendazole (a deworming agent), propranolol, and celebrex (or aspirin if well tolerated)

    But I don't know the dosage


    1. Hi again

      The choice of medications recommended here by Ben basically seems to me to be the 'Care Oncology Protocol' (Lipitor, Metformin, Doxycycline & Mebendazole) plus Celebrex (which is a very widely used off-label Cox-2 inhibitor) and Propranolol (which I don't know much about, but looks like it has a lot of studies behind it).

      My personal cocktail is very similar. Until very recently, I took Atorvastatin (1 x 20mg), Metformin (2 x 1000mg), Doxycycline (1 x 100mg), Mebendazole (1 x 100mg) and Celebrex (2 x 200mg). Since my liver readings were slightly rising since starting this cocktail, I decided to drop the Atorvastatin since a week ago. However, I did not have any other notable side effects on this cocktail.

      There is a quite a bit of discussion on the right dosage and effectivity of some of these meds, so you may want to read a bit on the blog (e.g. check the Care_Oncology_Clinic tab on the right, as well as run a search for the various medications. For instance, some people think that a much higher dosage than 100mg is necessary for Mebendazole to be effective.

      In my case, the dosage is based on the following trial:

      See also the related discussion here:

      For Celebrex the standard dosage here is generally around 400mg daily. Unfortunately, I am not sure about Propranolol.


  8. I should note that the Lipitor (brand name for Atorvastatin) is dosed up to 80mg per day in the trial link I posted, but should be raised slowly starting at 10mg, and then increasing to 20, then to 40, then to 80 every 4 weeks I believe. I wanted to be careful with this one, so stayed at 20mg only.


  9. Thanks John

    I have to ask if this cocktail should start concurrently with standard treatment (TM+RD 6 weeks ) or after this period?

    Thanks a lot John I appreciate your help

    1. Hi Syrian Os,

      I am not really sure if this would be a good cocktail for the Radiotherapy phase. I only started taking it afterwards, as a sort of maintenance therapy. During Radiotherapy some meds might be more effective I think, but it might be best to ask Stephen who has a much better handle on this than I do. As for me, I took Chloroquine (anti-malaria medicine... a lot of people here took this during radiotherapy and also beyond), Celebrex, Disulfiram+Iron (in an effort to lower MGMT expression).

      But I suggest you read around a bit on the blog for cocktail examples, e.g. here:


  10. Thanks for reply John

    This is Ben Reply to me
    (((What I recommend at present is a combination of old drugs: lipitor, metformin, doxycycline, and mebendazole (a deworming agent), propranolol, and celebrex (or aspirin if well tolerated). This is based on recent results from a clinic in London called Care Oncology Clinic. Google them for more info.

    These drugs, and the supplements you list should be taken concurrently with the standard treatment.)))

    So he said i have to use it during standard treatment..
    Whats your opinion??

    Also i have problem cause chloroquine Not Available in Dubai And i cant found online pharmacy to sent it to Dubai..


  11. Hi John

    Finally got Hydroxychloroquine 200 mg (Plaquenil), is it same of chloroquine?
    Can she take it?

    1. Hydroxychloroquine is similar to chloroquine, but not the same. The dosing is different, and also

      "Hydroxychloroquine is less lipophilic than chloroquine and does not diffuse as easily across cell membranes"

    2. Since the majority of malaria strains are now Chloroquine resistant, it seems like Chloroquine Phosphate (ie Aralen) is getting pretty hard to come by. I've seen it priced in the range of $10/gram.

      Chloroquine Phosphate is also for sale for use in fish tanks and is 20x cheaper (and no prescription needed), but who knows how pure/safe/etc it is. Anyone looked into this or have ideas on how to test for purity?

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