Phase II Results: TMZ with DISULFIRAM and COPPER (SNO 2018)

The disappointing results of this study are published in the SNO 2018 brochure:

http://sci-hub.tw/https://academic.oup.com/neuro-oncology/article-abstract/20/suppl_6/NP/5154662?redirectedFrom=fulltext

"ACTR-19. A MULTICENTER PILOT PHASE II STUDY OF CONTINUING TMZ WITH THE ADDITION OF DISULFIRAM AND COPPER FOR REFRACTORY GLIOBLASTOMA"

BACKGROUND: Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ). A previous phase I study demonstrated the safety of combining DSF/Cu with adjuvant TMZ for newly diagnosed GBM. This pilot phase II study aimed to estimate the potential effectiveness of DSF/Cu to re-sensitize recurrent GBM to TMZ. METHOD: This open-label, single-arm phase II study treated recurrent TMZ-refractory GBM patients with TMZ 150mg/m2 on days 1–5 of every 28-day cycle with concurrent daily DSF 80mg TID and Cu 1.5mg TID. Eligible patients must have progressed after standard chemoradiotherapy and within 3 months of the last dose of TMZ. Known IDH-mutant or secondary GBMs were excluded. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall (OS), clinical benefit (stable disease for at least 6  months), and safety. Evaluable patients must have received at least 28 days of DSF/Cu unless stopped due to progression, toxicity, or death.

RESULTS: From March 2017 to January 2018, 23 TMZ-refractory GBM patients were enrolled across seven centers in the United States, and 22 patients were evaluable. The median DSF/Cu duration was 48 days (range: 12–246 days). After a median follow-up of 4.4 months, there were no objective responses, with 6-month PFS of 14% and 6-month OS of 55%. Among 17 patients who had at least 28 days of DSF/Cu, 3 patients (18%) had clinical benefit. Grade 3 toxicities that were possibly related to DFS/Cu included fatigue, headache, anxiety, and elevated alanine transaminase (5% for each).

CONCLUSION: Addition of DSF/Cu to TMZ for TMZ-refractory GBM yielded minimal ORR but demonstrated clinical benefit for a subset of patients. DSF/Cu may have modest TMZ re-sensitization or single-agent activity for recurrent GBM.

Disulfiram Interactions?

Has anyone had personal experience (or that of a loved one) using rubbing/isopropyl alcohol while on disulfiram? Optune requires the use of 70% rubbing alcohol on a freshly shaven scalp and am concerned about a potential disulfiram reaction. There are numerous warnings about this by the makers of disulfiram, but am hoping to learn about personal experience with this.
Similarly, has anyone used CBD tincture (typically manufactured using alcohol) while on disulfiram? 
Gratitude and healing wishes for all souls using this wonderful forum.

Drug Cocktail for Newly Diagnosed GBM

Hi Everyone,

I'm new to the blog and blogging in general. My brother is 3 weeks post op craniotomy for removal of 2cm brain tumor in left frontal lobe - complete resection was not possible but approximately 80% removed. Otherwise Joe is a healthy 35 yo male

Pathology report came back:
Grade IV Glioblastoma, wild type
Negative IDH1/2
Negative MGMT methylation
No amplification of EGFR gene

He will be part of a clinical trial with proton therapy radiation at MGH in Boston.  Joe is gripped by depression but committed to starting treatment - hopefully along with a drug cocktail. I've been helping him research and pull it together. When he starts radiation and chemo in a week or so I would like him to be on below meds / supplements

Drug	Dosage
Valproic Acid	1000mg
Chloroquine	250mg daily
Celebrex	200-400mg daily
Fluoxetine	40mg daily

Supplement	Dose
CBD / THC	gradually increasing dose
Boshwella	1000mg
Green Tea
Curcumin	1000-2000mg +
Melatonin	10-20mg
Maitake D	100mg
Fish Oil
Probiotic
Turkey Tail - ie PSK	3000mg
Vitamin D3	5000-10,000 UI
quercetin	500mg
milk thistle	1000-2000mg
Reishi mushroom

This is not a complete outline as I'm using some supplements he purchased and some meds he is already on (valproic acid).  I would love to have any suggestions or thoughts.

I also have some questions for you all (I'm sure the first of many) 

1. How open are neuro oncologist to a cocktail approach? Joe is afraid of asking them about adding anything to the current standard of care 

2. Is it true that unmethylated MGMT tumors are not as responsive to TMZ? Should we ask about a metronomic everyday low dose? What is the current dosing of TMZ in standard of care?

3. Should we look into adding Antabuse, Metformin, or an ACE Inhibitor? 

Best, 

Jenna

*my apologies for any typos 

Thoughts on ALA and Hydroxycitrate

Hi all,
I haven't posted before and am fairly new to the blog. I've been visiting it frequently over the past few weeks and I really appreciate all of the shared knowledge, opinions and helpful advice that I see here.

I am wondering if anyone has tried the alpha-lipoic acid/hydroxycitrate combination in addition to CCNU. My husband is 31 and is about to begin his second round of chemo, this time trying CCNU. He was diagnosed last April and went through the standard TMZ/radiation but had a recurrence in January. He had his second surgery in February and they were able to do a complete resection this time.

I've been reading a lot about alpha-lipoic acid and hydroxycitrate, also in combination with naltrexone, and I think it's something we want to try. I'm wondering if there are certain supplements or medications he shouldn't take at the same time... also curious what the recommended doses would be. Some of the studies I've read show that the ala was administered via IV which I don't think will be possible for us, especially because I expect his oncologist to be really hesitant about this treatment plan.

Also, is it possible to combine this type of treatment with CCNU and another drug like tamoxifen or Keytruda? So many options and I'm not sure which is the best to make a case for to his doctor.

He takes a number of supplements, including turmeric, garlic, goldenseal, resveratrol, boswellia, and vitamin D. He's also on metformin, a dose of 500mg twice a day. He's been on the ketogenic diet for almost a year.

I appreciate any insight.
Thanks!

Abby

*Edit: I should also mention that we are still waiting on the more extensive genetic testing results. His first pathology last year showed MGMT methylation-positive, IDH1 positive. ip19q negative.

Strengthening the effect of CCNU + TMZ

My mom will soon take next course of Lomustine + 5 days of Temozolomide.

To enhance the effect of this combination only these days we want to take also:

1. Disulfiram 500 mg + Copper 4mg + DHA 1200mg / day
2. Verapamil 300-400 mg / day (doses of 40 mg every few hours, so that blood pressure does not go down much)
3. Curcumin Longvida 2000mg, EGCg 2000mg / day
4. Alfacalcidol 2 mg / day
According to this study: https://www.ncbi.nlm.nih.gov/pubmed/27313664
Autophagy enhancement contributes to the synergistic effect of vitamin D in temozolomide-based glioblastoma chemotherapy.

Are there any other ideas that can enhance the effect? I have not forgotten anything?
Since my mother takes Lomustine and Temozolomide according to the Ceteg trial every 42 days, I do not want to miss anything.

In addition to these additives our main cocktail includes:
1. Delagil 300 mg / day
2. Bevacizumab 7,5mg/kg/3weeks
2. Sirolimus 2 mg / day (possibly, it will be reduced to 1 mg because of Varapamil)
3. Telmisartan 80 mg (will be canceled for this period because of Verapamil)
4. DCA + caffeine (will be canceled for this period because of Disulfiram)
5. Inhalation with perillic alcohol (will be canceled for this period because of Disulfiram).
    - After Disulfiram, when we can start inhalation again? Probably need a break.
    - Perhaps, for the effect of Disulfiram it is necessary to take it constantly, and not only in the days of Lomustine + Temozolomide? Perhaps, Disulfiram will not have an effect only in these 6 days?
____________________________

I also found this research:
Lithium enhances the antitumour effect of temozolomide against TP53 wild-type glioblastoma cells via NFAT1/FasL signalling.
2017 https://www.ncbi.nlm.nih.gov/pubmed/28359080
"Temozolomide combined with low-dose Li induces TP53wt glioma cell death via NFAT1/FasL signalling. This represents a potential therapeutic strategy for TP53wt glioma treatment."

However, I can not understand is the wild type TP53 our case?
http://btcocktails.blogspot.ru/2018/02/our-report-oncodeep-what-do-you.html

Our cocktail and report "OncoDeep". What do you recommend to pay attention to?

Since the tumor after surgery (removed 99%) increased again in the same size (3.5 x 5 x 5 cm) in 3 weeks and the tumor did not decrease after radiotherapy + TMZ, we probably have a very unusual cocktail for the first line:
- cycle 42 days: Avastin (3mg/kg/week) + CCNU (1 day 75mg/m2) + TMZ (5 days 90mg/m2),
- disulfiram 500mg (+Copper 5mg + DHA) and verapamil 200mg only on the days of TMZ + CCNU administration, and 2 days before and after.  I'm not sure, maybe it's advisable to take Disulfiram every day? Otherwise, disulfiram may not start to influence so quickly?
- every day: cloroquine phosphate 250mg, telmisartan 80mg, alfacalcidol 2mcg, oxaloacetate 100mg,  melatonin 20mg, curcumin longvida 2000mg,  Berberine 1000mg, DHA/EPA 1000mg, PSK / PSP 1800mg, Methimazole + T3, R-lipoic acid + hydroxycitrate + ketogenic diet, omeprazole 20mg + DCA 20mg/kg (10mg/kg/BID) + caffeine (2 cups of coffee and 5 cups of black tea) + vitamin B1 200mg

My mother has been responding well to taking DCA + caffeine for a week in the form of black tea and coffee. However, my mom's pulse increased to 90-95 after sleep or rest. To reduce it, we now take 10 mg of propranolol per day. An increase in the pulse may also be caused by the intake of the hormone T3.

Also I consider the addition of a low dose of naltrexone before bed.
We also ordered perillyl alcohol at www.sigmaaldrich.com and expect it soon.

Today we received a report from OncoDNA. The last 3 months I read and search for any information about glioblastoma, but unfortunately I find it difficult to understand this report. Doctors in Russia do not order such reports at all! Our doctor in Germany said that unfortunately, such reports will not help us in any way.

Maybe you can tell me what to look for in this report? Any comments?

For example, I can not understand, is there overexpression (amplification) of EGFR?
"Damaging TP53" = mutation of TP53? Not understanding this, I can not draw conclusions from this review (http://astrocytomaoptions.com/exploring-strategies-for-tp53-mutated-gliomas/) and other studies.
"Damaging PTEN" = loss or mutation PTEN? An interesting article in this case: http://btcocktails.blogspot.ru/2018/01/parp-inhibitors-for-pten-mutant-cancer.html
Which of the drugs on the list of potential clinical benefits to pay attention to ?

Here is a link to the report itself and some pictures of him:
https://drive.google.com/open?id=1A3dophOME6gY1GNdOHWE48wVYJUu_nHc

 

 

Final results of disulfiram pilot trial for newly diagnosed GBM

Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma
http://sci-hub.la/https://link.springer.com/article/10.1007/s11060-018-2775-y

Sadly, median PFS and OS were not improved above historical controls receiving standard treatments alone.

However, only 6 of 18 patients also took copper supplements in this trial in addition to disulfiram, leading to another phase 1/2 trial of disulfiram + copper for newly diagnosed GBM which is still recruiting.
https://clinicaltrials.gov/ct2/show/NCT02715609

Treatment options post-RT/TMZ phase for IDH1 mutated, MGMT unmethylated GBM

Hi all,

I was diagnosed in late September with a GBM (frontal, left, with large cyst, IDH1 mutated, MGMT unmethylated), which was subsequently successfully operated (gross total resection) at the end of September. I guess as many/most here, I eventually stumbled across Ben William's book, the Glioblastoma Treatment options guide and ultimately this invaluable blog and community, which I have been studying and following closely since. I recently concluded the first phase of my treatment, following standard Stupp Protocol (6 weeks concomitant RT/TMZ) and am currently planning next steps (plus waiting for first post-RT MRI next week...).

While I did not get 'smart' in time to save my tumor material from being paraffined post-OP (unbelievably, this is still standard practice here in Germany in most hospitals), I did actively supplement my first phase of treatment with what I think is a reasonably aggressive 'cocktail' approach, including the following components:

--------------------------------------------------------------------------------------

Meds:
- Chloroquine, 1x 250mg
- Celebrex, 2x 200mg
- Disulfiram, 1x 250mg - 500mg (+4mg copper)
- Sativex (THC/CBD spray), ca. 3-4 sprays (approx. 15-20mg)

In general, I tolerated these medications without any major problems or side effects, with a few exceptions. Notably, towards the end of the treatment I developed some peripheral neuropathy in my left foot, which has now almost recovered, however (took around 3-4 weeks to recover). Nevertheless, it cause me to cease the Chloroquine and Disulfiram shortly before the end of my RT treatment phase. In addition, I found it a little hard to tolerate Sativex as I wasn't too keen on the psychoactive effect, which gave me some anxiety / mild panic attacks from time to time at night. As a result, I took it only for around 3 weeks or so.

Supplements:
- Berberine: 1000mg
- Boswellia Serrata: up to 4400mg (gradually increased dosage over course of RT to protect from Edema)
- CBD oil (8%), 5 drops (started after ceasing to take Sativex)
- PSP, 2100mg
- Curcumin (Longvida), 2000mg, increased to 3000mg towards end of treatment
- Green Tea Extract, 3625mg
- Lycopene, 20mg
- Matiake D-Fraction Pro, 65mg (3x 23 drops)
- Melatonin, 20mg
- Omega 3 DHA/EPA, 3528mg
- Probiotics, ca. 40bn units
- Pterstilbene, 250mg
- Resveratrol, 500mg
- Selenium, 200ug
- Silymarin, 1500mg
- Soy extract, 3750mg
- Vitamin D, 9000IU

In general, all of the above were well tolerated without side effects. I'd also like to mention I was able to avoid any kind of Edema / Cortisone use during my RT therapy, which I believe may have been at least in part facilitated by Boswellia in combination with Celebrex.


Other:
- Ketogenic diet, max 40 g Carbs per day; generally constant medium to high Ketone bodies when measuring. Started 1 week before RT, and continued to last day
- Caloric restriction, lost ca. 8 kilos in 6.5 weeks of RT, which I think equates approx. 600kcal or so in daily caloric restriction
- Daily morning smoothie, with variety of hopefully beneficial things like berries, broccoli sprouts, spirulina, tumeric powder, Matcha green tea, cocoa powder,  etc.
- Daily walks of ca. 1 hour to combat radiotherapy fatigue and keep fit

Ketogenic diet was somewhat difficult to maintain psychologically, but possible due to my partner's kind help in continuously seeking out new and often tasty dishes to keep things interesting. Caloric restriction much easier, since Temodal anyway caused me lack of appetite. I believe daily walks were very helpful to avoid RT fatigue, which affected me only in very minor way and much less than I expected.

--------------------------------------------------------------

NEXT STEPS & QUESTIONS

I am currently considering next steps, and having talked to various NOs and other Brain Tumor specialists, I am still not entirely convinced what the right way forward is. As expected, most doctors do not want to deviate from the Stupp Protocol (i.e. follow up the RT/TMZ phase with 6 months of 5/23 TMZ cycles). However, I am not convinced such a treatment would necessarily add much benefit in my case, since my tumor is MGMT unmethylated.

One of the leading specialists in Germany told me that the unmethylated MGMT status is irrelevant in the case of IDH1 mutated tumors like mine, since a study (NOA-4) showed that there was no significant difference in responsiveness  between MGMT methylated or unmethylated IDH1 tumors.

https://www.ncbi.nlm.nih.gov/pubmed/19901110

However, upon further research I stumbled across the following interesting study from China, which seems to suggest that IDH1 mutated tumors might in fact be particularly resistant to TMZ (3-10x more resistant in cell culture test). The study also notes that in China they observed relatively little additional benefit of TMZ cycles for the IDH1 mutated group of patients compared to RT alone, and the authors argue that survival benefits for IDH1 mutated tumors may simply be the result of a less invasive / more benign type of tumor relative to wildtype. It makes me wonder if the fact that MGMT doesn't seemingly play as big a role for IDH1 mutated tumors is simply the result of the fact that neither responds well to TMZ...:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747376/

I'm therefore a bit hesitant to simply go ahead with TMZ therapy hoping for the best, and would like to consider other options.
One approach I am considering is Immunotherapy at the IOZK clinic in Cologne, which is not far from my house. However, because I don't have frozen tumor material, they would have to make a personalized vaccine using a liquid biopsy approach. This, in turn, could make the treatment even more unproven than vaccines anyway are even when made from tumor lysate. An additional option which could possible materialize down the road (but not yet, as no trials are running here presently to my knowledge) is to try to get hold of an IDH1 vaccine on a compassionate use basis.


My immediate next step is to see the MRI results next week, but I'd be very grateful for any advice on how to proceed from here. Especially, I'd like to try and resolve the following questions:

1. Would it be unwise to not do any additional TMZ cycles? Are there any obvious chemotherapy alternatives perhaps?

2. Would the immunotherapy using liquid biopsy at IOZK clinic be a good alternative for ongoing chemotherapy cycles? Would it be advisable to start this right away (i.e. without any additional TMZ cycles), or should I do some TMZ cycles first just to hedge my bets?

3. Any other recommendations in terms of maintenance strategies. E.g. what medication(s) could make a good maintenance therapy, without concurrent chemotherapy?


Thanks in advance for any comments, and wish you all a very happy and most importantly healthy 2018!

Best,
John

Disulfiram + copper + radiation + TMZ case report

While not providing definite evidence of disulfiram activity, this case study on the use of disulfiram + copper for an IDH1-mutant, MGMT-unmethylated glioblastoma does show that disulfiram therapy can be initiated at the time of radiation.  The disulfiram dose was 250 mg daily, and the dose of copper gluconate was 3 mg twice daily.

Evidence for the efficacy of disulfiram and copper combinationin glioblastoma multiforme - A propos of a case

Disulfiram and alcohols

I was thinking about disulfiram and alcohols - does it interacts with ethanol and methanol only? What about sorbitol, mannitol etc? Should all "-ols" be avoided in diet?
Mainly what about perillyl alcohol - it is monoterpene but does it have something in common with alcohol?
Can you take them simultanesly- disulfiram and perillyl alcohol (solution with NaCl only)? What are your thoughts and experiences?
Bb

New disulfiram trial in Sweden

DIRECT (DIsulfiram REsponse as add-on to ChemoTherapy in Recurrent) Glioblastoma: A Randomized Controlled Trial

This is a randomized phase 2/3 trial with an expected recruitment of 142 patients recruiting in Norway and soon to be recruiting at multiple centers in Sweden.

One arm gets standard alkylating chemotherapy at recurrence, and the other arm gets standard chemotherapy plus disulfiram and copper.

NCT02678975

Disulfiram when combined with copper enhances the therapeutic effects of temozolomide for the treatment of Glioblastoma.

View study here

This study is exciting as it is the first study of disulfiram + copper in orthotopic GBM patient-derived xenograft mouse models.  Disulfiram and copper were given orally, not by injection, at clinically relevant doses.  The disulfiram + copper had little effect on its own in the mice, but sensitized the tumors to TMZ.  The testing was done on both newly diagnosed and recurrent samples.

disulfiram side effects ?

Hi everyone my dad finished his 6weeks of radio plus chemo on the 2nd of feb and a gave him a break from the whole cocktail approach. I've added a few more things to the cocktail aswell and I am starting him on one drug and introducing another 4-5 days after. He started chloroquine phosphate 5 days ago and I added Disulfiram yesterday. Everything seemed good no side effects but today dad's been sick and light headed I know that there is a lot of alcohol in most house hold products but how sensitive is it to alcohol ?

Keppra and Temozolomide

Hi Everyone!

I'm new to this blog. I've read many posts and this is a great help to me, as I'm a beginner in the drug coctail treatment.

Our story briefly:
1) My father, 55, was diagnosed with an unknown brain tumor in October 2015 (the biggest dimension 43 mm). Craniotomy was carried out 3 days after the diagnosis. Preliminary histopathology - astrocytoma III, final result - glioblastoma IV.
2) First MRI after the surgery in December, right before chemoradiation, showed still a big tumour. According to the oncologist - radical recurrence. According to another neurosurgeon (we consulted the MR image in another hospital) - first craniotomy improperly done (!!). I'm not sure who's right... the other neurosurgeon, specialized in gliomas, was very convincing.
3) We decided for another surgery (by another surgeon). The resection must have been deeper as afterwards my dad's sight is worse (he sees everything darker, has problems with reading, seeing details etc., however he's getting better, it's been 6.5 weeks since the surgery).
4) Now chemoradiation. First cycle of Temodal during radiation for 42 days on a daily basis.
5) Tumour unmethylated, IDH1 negative. Other genetical tests of a frozen sample in progress.

We are at the very beginning of the drug&supplements treatment. It's very difficult to collect all the prescribed drugs. We're located in Poland. Started like that:
Temodal (150 mg/day);
Depakine (valproic acid) 2x500mg/day- prescribed by the neurosurgeon to prevent seizures;
Keppra (will start tomorrow, 2x500 mg/day)- added in order to sensitize the tumour for TMZ (prescribed by our GP on request, she agreed);
Dexamethasone (2 mg/day);
Proton pump inhibitor (1x/day) - drug called IPP20 in Poland;
"Pheonix tears" with high THC and CBD (rectal application) - 2 ml/day
Curcumin (up to 3000mg/day)
Quercetin
Vitamin C (1000 mg/day)
Sugar-free diet and radical reduction of meat. Working on reduction of gluten.


I have one question and would be grateful if anyone could advise sth:
What would be the best scheme of taking Keppra to sensitize the tumour for TMZ. Does it matter, if the first doze (500mg) is taken with Temodal on an empty stomach or he can take it later, after his daily radiation (with a meal afterwards)?
Should we add Prozac and Disulfiram, apart from Keppra, for a better chance of TMZ working?


Cheers!
Piotr

Effect of Disulfiram Administration on Rat Brain Glutathione Metabolism

http://www.ncbi.nlm.nih.gov/pubmed/8142069

This study is not about brain tumors, but it does show that oral administration of disulfiram to rats (12 mg/kg), which would convert to about 125 mg for an average adult using allometric scaling, is sufficient to decrease the brain levels of reduced glutathione (GSH), increase the levels of oxidized glutathione (GSSG), and thereby decrease the ratio of reduced to oxidized glutathione from 122:1 to 12.8:1.

I propose that this could be a particularly effective therapy in IDH1-mutant tumors, which already have lowered baseline levels of NADPH, reduced glutathione (GSH) and impaired antioxidant capacity.

I will add this study to the Library.

A typical anti-alcohol abuse dose for disulfiram is 250 mg daily (500 mg has also been used).  Watch out for peripheral neuropathy (pain, tingling, numbness in fingers, toes, etc.).

verapamil and TMZ

Stephen,
. IF I was to take verapamil with temodal do I need to start the verapamil a few days before starting temodal also if that is correct and once that is established can I take both drugs at the same time? Would it effect the absorption of temodal? I wanted to take them so they are both in the system at peak plasma times. From what I've read the  time to peak plasma concentration for temodal is 1 hour, half life 1.8 and Verapamil immediate release is 1 - 2 hours for  and half life is 2.8 to 7.4 hours Verapamil extended release with food is 12hours to peak plasma concentration and without food 7 hours. as per link below.

I have both immediate release and slow release but not sure how Alan will respond so not sure if we'll end up taking the SR or the immediate release. Do you know what the best time frame to maximise  Verapamil's multidrug resistance effect along with Temodal for both slow release and immediate release would be.
http://www.medsafe.govt.nz/profs/datasheet/v/VerpamilSRtab.pdf

Lomustine, Carboplatin, Irinotecin... which would you pick?

All -

Dad's oncologist believes that given his decline while on Temodar we should try another option for our next round of chemo in a few weeks.  She said that the choices are Lomustine, Carboplatin, and Irinotecin.  Dad is also taking Avastin (started last week).  Our full cocktail is posted to this blog.

If you had the option to 'pick', which would you push for?  We don't have any genetic testing.  Dad's tumor had a biopsy but no surgical resection.  I've been trying to obtain his MGMT methylation status but it has been nearly impossible to request the test.  Lots of back and forth with nothing.

I'm now beginning to research these three options but want your opinions as well.

Thanks as always..
Annie

Disulfiram and DCA

After Jeremy finishes his 12th round of TMZ end of next month I plan on having his take disulfiram on a daily basis in an attempt to go after CSC's.   Who is using both disulfiram and DCA concurrently and are you have any difficulties with PN?  Are you rotating on and off disulfiram?  The question that comes to my mind is whether disulfiram use intermittently will result is disulfiram resistant CSC (assuming it works at all).  Sort of like taking an antibiotic for a bacterial infection might result in antibiotic resistant bacteria if the drug is not taken for a long enough duration.  But then this has to be considered in light of developing PN.  Additionally, what dose of disulfiram is being used with those combining DCA wand disulfiram?  Any thoughts will be much appreciated.  Thanks in advance.

Dosing DCA ,Disulfiram together

Please correct me if I am wrong.

So both Disulfiram and DCA cause neuropathy. I am trying to dose both.

DCA can cause memory problems and hand tremors and possible Korsakoffs syndrome which could be very serious and what  I am worried the most about. Of all the patients treated by Medicore they did not mention that side effect of DCA but in theory it is possible.

So this Korsakoffs is caused by not enough vit B1. 

Neuropathy caused by Disulfiram is caused by other mechanism  I assume and not by vit B1 depletion. CUSP 9 doctors are not supplementing with B1. 

In that case Disulfiram would never cause Krsakoffs or memory problems because it does not deplete vit B1. So dosing Disulfiram even if taken with DCA I wouldn't have to worry about heart failure, or memory problems. So even If vit b1 is low and I stopped DCA I can still give Disulfiram. Is that correct?

Disulfiram and copper

Steven

Do you know what dose of copper would be used with disulfiram?  Being copper seems to be involved in cancer growth if not initation, it seems that the lowest dose of copper should be used.

Also, I am of the belief that it is the copper that is beneficial, not the gluconate component (the study specified CU gluconate)  Typically we see various chelated forms of minerals have different bioavailabitly, but it is the mineral with the therapeutic effect.  In the disulfiram/copper combination I suspect this is the case as well.  Do you know if there is something special about this particular copper preparation that gives it synergy with disulfiram?