I'm so desperate to help him defeat this nasty disease. I know that I'm too hesitant and that we don't have time for that. My husband was shocked about his diagnose so he don't want to read about the possible treatments and drugs so everything is on my shoulders. I totally understand his attitude although it would be such a great help if he would be proactive because he is the smartest person I've ever met. His NO is a very good professional but absolutely not on board, just SOC. We don't even have the courage to ask for his opinion.
Unfortunately we started the majority of these drugs only after radiochemotherapy (except of Metformin and alfacalcidol). We added Aciclovir and CQ on the last week of the radiation therapy. Fluoxetin and DCA right after the last day of RT. Celebrex only 2 weeks ago.
He weighs 70 kg (ca. 154 pounds) if it matters.
Official:
Medrol 16 mg (chorticosteroid - in Hungary we don't have Decadron) This is one tablet only and I'd like to reduce it by half because we have Celebrex but my husband is hesitant because we only have appointment to the NO on 21/8. He has no symptoms other than extreme fatigue and metallic taste in his mouth.
Prescription drugs:
- Metformin - we recently increased it from 850 mg to 1275 mg (This is 1.5 tablet)
- Chloroquine 250 mg
- Fluoxetin 20 mg (Should we increase it to 40 mg? He is quite depressed even after more than a month on it so it just would be a bonus if his mood would be better.)
- Celebrex 200 mg x 2
- DCA 500 mg x 2 on a 2 week on 1 week off basis. We'd like to increase it to 500 mg x 3 as soon as he finishes his first TMZ cycle. Up until now he has not experienced neuropathy although he takes 1 pill of Milgamma Neuro every other day which contains 40 mg of benfothiamin, 90 mg B6 and 0,25 mg B12. We use the product of DCA Lab.
- alfacalcidol 2,5 mcg
Around chemo days:
- Aciclovir 400 mg x 2 (I'm just guessing what would be the right dosage and maybe he should take it daily, not only around TMZ days.)
- Omeprazole 40 mg x 2
His Canadian friend will bring him cimetidine within a few weeks. I'd like him to take 1000 mg a day.
I've just read about clomipramine here but I suppose that you can't use clomipramine and fluoxetin together. Which one has more benefit in your opinion? Mouse evidence on one hand and lots of anecdotal success stories on the other hand.
My husband never had a seizure so I'm hesitant to give him Keppra although its chemosensitizing properties are very tempting.
I have propranolol and I'm thinking to start my husband on it after the first MRI but I'm afraid to mess with his blood pressure. Based on the etodolac + propranolol trial I hope it can be effective with the standard 5/23 protocol, too. I'm assuming that Celebrex can be an appropriate alternative to etodolac.
Although we have a good relationship with our GP who is helpful enough to prescribe for us the above mentioned drugs, I think that she would be reluctant to prescribe tamoxifen, disulfiram, minocycline or maybe even mebendazole on the long term. What do you think of such providers like Alldaychemist? Is it risky to buy from them? Any personal experience?They even have Valcyte which I haven't been able to convince anybody to prescribe since my husband is seronegative for CMV. He had it once but now he has no active CMV infection.
Non-prescription:
- Genistein (Soy Isoflavones) 28 mg x 2 (We are not so convinced about it and my husband hates it so I think I'm not going to buy it again.)
- Silibinin 86,5 mg x 6
- melatonin 20 mg
- ca. 1 dl / 3 oz (?) frozen breast milk except of TMZ days (I know, I know...but it was easy to get it through a reliable relative.)
- propolis (30 drops)
- 1 liter green tea on TMZ days with Omega 3 and 200 mg ascorbic acid
- 1 teaspoon of home-made ethanolic rosehip tincture daily (except of TMZ days) because of this study http://www.scirp.org/
I know Stephen what you think about in vitro results but it's so easy to make and it can't do harm.
During RT he ate tons of lycopene-rich tomato juices and home made rosehip puree and steamed broccoli and broccoli sprouts because of sulforaphane. The latter now he hates so he'll start soon on broccoli sprout capsules. I also give him fresh pomegranate juice almost every day.
As you can see we are not so eager about supplements, they seem a bit unproven for us but I recently ordered Longvida curcumin (although its poor bioavailability), liquid Maitake D fraction, Selenium and CQ10.
Is CQ10 and Selenium applicable in between TMZ cycles despite their strong antioxidant properties?
Also, we tried a popular Hungarian medicinal mushroom complex (8 pills contain 150 mg rezveratrol, 336 mg shiitake, 336 mg ganoderma, 336 mg maitake, 336 mg almond mushroom) but he had severe diarrhea even on 2 pills a day so I'm not so confident to order him the Mushroom Science PSK product that everyone uses. I didn't see anybody encountering this problem on any cancer forum. It would be a pity to miss it.
I bought some edible oregano essential oil because of these articles but we don't know how to administer it. First, he tried to dissolve 5 drops under his tongue but it has awful taste. Later he tried to drink 5 drops with water. It's also a very strong antioxidant so maybe it's not so smart decision to use it when he is on DCA. or in between chemo cycles.
https://www.linkedin.com/pulse/oregano-compound-activates-oocytes-kills-glioblastoma-finley
https://www.ncbi.nlm.nih.gov/pubmed/25965832
We'd like to obtain 1:1 THC-CBD oil, too. Could you please provide me with some reliable resources? A lot of people seem to take it but I don't know where to buy it.
Big thank you to Stephen and this helpful community.
Hello Ildi,
ReplyDeleteThere is a lot of information and questions here, I will try to help with at least some of them.
What is your husband's age and diagnosis (glioblastoma? anaplastic astrocytoma?). Was there any testing on the tumor tissue for MGMT methylation status? IDH1 status?
16 mg of Medrol (methylprednisolone) would be equivalent to about 3 mg of dexamethasone. http://clincalc.com/corticosteroids/
This is a moderate dose, and it's good if you're able to keep steroid dose under 4 mg of dexamethasone or equivalent. There is some evidence that high dose steroids can interfere with radiation efficacy.
40 mg of fluoxetine is a mid-range dose, so increasing up to 40 may help with the depression and may also help sensitize the tumor to TMZ (through effects on MGMT expression), and may have anti-tumor effects on its own as well.
2.5 mcg alfacalcidol is approximately the same dose used in the 2001 study for GBM, (0.04 micrograms per kg) but it would be a good idea to have his blood checked for signs of hypercalcemia with prolonged use.
There is very little evidence for use of acyclovir for GBM. Some have suggested it could be used as a cheaper alternative to valganciclovir (Valcyte), and some have hypothesized it could be useful to aid antitumor immunity as an IDO inhibitor (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925358/), however solid evidence is lacking.
Combining an SSRI like fluoxetine with a tricyclic like clomipramine is not necessarily absolutely contraindicated, but could theoretically lead to problems such as serotonin syndrome, and it would be advisable to be closely monitored by a doctor if such a combination were attempted. To choose one, I guess it just depends what kind of evidence you trust more: well-documented mouse evidence, or less well-documented human evidence (unpublished observations of some patients "doing well" on clomipramine).
There is some human evidence of Keppra possibly being responsible for a reduced MGMT expression observed in GBM tumors. It would be useful to know the MGMT status of your husband's tumor to help with this decision, if Keppra isn't needed for seizure control.
Celebrex and etodolac may have similar effects, as they are both approximately equally potent and selective as COX-2 inhibitors. The outcomes of the propranolol + etodolac + TMZ trial did look very impressive, unfortunately the documentation of that trial is minimal (a single abstract, with even the abstract missing crucial details). There is theoretical justification for using a drug such as propranolol, and there is human observational evidence supporting its use for other cancers as well.
I have no experience purchasing drugs through online pharmacies, so other blog members will have more information for you on this. There is also a "pharmacies" label in the list of labels to the right, so you can review past discussions on this topic.
ReplyDeleteYes, in the hierarchy of evidence, in vitro evidence sits at the bottom of the pyramid, mainly because drug concentrations used in vitro usually bear no resemblance to achievable concentrations in human plasma (let alone central nervous system). But I agree there is probably no harm in many of the supplements that have less than compelling evidence, and they may do some good.
Unformulated curcumin has poor bioavailability, which is the very reason to purchase formulations with improved bioavailability of free curcumin, such as Longvida.
The debate about antioxidants during chemotherapy/radiation is beyond the scope of what I can write here. I'd refer folks to Ben Williams essay on the subject. http://virtualtrials.com/pdf/williamssupplements2014.pdf
I will say that some "antioxidants" have actually been shown to work well with TMZ chemotherapy in mouse models, for example EGCG. Many compounds labeled as "antioxidants" have multiple additional mechanisms of action, so we can't always predict whether an agent will work with, or against a conventional treatment, simply on the basis of it being an antioxidant (among many other things).
His problem with the mushroom mixture may be a problem with that particular product. I wouldn't give up on mushrooms altogether, but try something different.
As for the oregano, again this is based on in vitro evidence. If there are 1000 things that have evidence in GBM cell culture studies, there might be 50 things that have evidence in mouse studies, and 10 things that have evidence in high-quality mouse studies, and even fewer agents that have compelling human evidence. It is an evidence pyramid, and I tend to focus on the things with higher quality evidence. I will add you to my Brain Tumor Library, where you'll find my spreadsheet called "Pharma and non-pharma list", where I've attempted to bring at least some order to the cocktail decision chaos people find themselves in.
I'm not aware of the legal status of cannabis products in Hungary. Sativex (THC:CBD) has been approved for sale in a number of European countries (including Czech Republic, Slovakia and Austria), so perhaps you could access it one of those neighboring countries.
Thank you so much Stephen for your detailed answer, it was really helpful. Sorry, I forgot to mention that I wrote the previous post, too, where I posted the details about my husband's status. He is a 29 years old GBM patient, IDH negative, has no EGFR amplification. We don't know his MGMT methylation status yet.
DeleteThank you, I'll definitely look into the "pharmacies" label. A month ago I contacted GW Pharmaceuticals whether they could provide me with Sativex directly, referring to the Sativex trial for recurrent GBM, also stating that I can get prescription from our NO (which is not definitely true but I was curious). I didn't received any response so far. Things like that I don't want to order from shady sites where you can pay only with bitcoin.
Hi Ildi, just wanted to comment on Sativex, please bare in mind its just my opinion. My son has GBM and I had the option of getting Sativex, but chose not to as it has very low levels of THC in it. Sativex is high CBD, which really helps with nausea, but if you want to actually treat the tumour then you need high CBD and THC. For this reason I make my son's Cannabis tincture myself.
ReplyDeleteCheers
Brad
Sativex has an approximately equal ratio of THC and CBD. It contains 2.7 mg of THC per 100 microliter spray and 2.5 mg of CBD per spray.
Deletehttp://omr.bayer.ca/omr/online/sativex-dhcpl-lapds-08-01-2007-en.pdf
Making your own tincture though likely saves a lot of money and allows easier administration of high doses of cannabinoids. The sprays like Sativex are more suited to low doses, with a recommended dose of 4 - 8 sprays daily (amounting to 10-22 mg of THC and 10-20 mg of CBD daily).