Second recurrence-- what next?

Hi all,

My husband is being treated for his second GBM relapse. He's receiving irinotecan and Avastin at the moment and his last two MRIs have been stable, interpreted as radiation necrosis. The tumor size hasn't changed at all (close to 4cm in diameter) and he's experiencing neuropathy on his right side, speech difficulties and major brain fog on some days, but overall doing okay. In fact, he has improved significantly since July, when he could barely form sentences, was losing function of his right side and was very sensitive to noise and light. Now he's going on daily walks, can spend time around our rambunctious kids, and his speech is much better-- we are feeling very grateful.

I'm considering adding to his cocktail but I'm not sure what to add and what we should prioritize when talking to his doctor. Here's what I'm considering, I'd be open to any suggestions beyond this as well. His tumor is MGMT-methylated and IDH1-mutant.

-Chloroquine-- Is this something we would have to source on our own? And if so, is it still not available in the U.S.? Has anyone purchased from the vendor in Canada?

-Mebendazole-- What is the recommended dosage for this? Is it potentially more effective than chloroquine?

-PARP inhibitor-- Is there off-label use approved with olaparib in the U.S.? And can this be used with his current treatment?

-Disulfiram- Is this potentially a bad idea if he's already experiencing neuropathy?

-Sodium phenylbutrate-- I haven't read too much about this one other than a couple of successful case reports. I'm assuming this is something we'd have to get his doctor to prescribe but I'm not sure if it's worth pursuing.

-Sativex (or similar)- Where is this available? And what is the recommended dosage?

I think I'm most interested in introducing mebendazole, disulfiram, Sativex and a PARP inhibitor, if possible. Interested to hear others' experiences with any of these.This blog/community is an excellent resource-- thank you in advance!

Abby

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:

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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.

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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

Understanding Cannibas benefits/dosage (separating out CBD from THC)

Hello Lovely Group,

In need of some cannabis education!

There seems to be LOTS of info on using Cannibas in Brain Tumors for various reasons.  I'd like to understand this more so that my husband can get some relief (who's biggest issue lately is sleep disturbance).  However, I'd like to learn all the benefits of Cannibas for brain tumors and learn best doses to get the most healing out of this substance.

Here are the issues that we hope to improve and/or resolve with cannabis:
1. Improve night time sleep (less waking up and less trouble falling back to sleep)
2.  Decrease inflammation/swelling:  He's post 2nd tumor removal surgery and it takes longer to heal 2nd time around (especially after all that radiation and he was on plerixafor study which exacerbates radiation effect) so he's had lots of treatment swelling (results in speech stumbling and word finding issues).
3.  Improve Daytime alertness:  He's back to work at a busy job and could CBD give him more alertness and  energy for the day.
4.  Decrease risk of seizures (he hasn't had any lately, but hoping the cannabis on board will keep his seizure risk low. 

NEXT Question is How Much?  Dose, Dose Range, in what form-edible, oil, leaf, smoke, ingest?

I've heard that it's best to separate out the THC from the CBD.  (THC for night/sleep)\ CBD for Day use).  Is that a correct understanding? 

THC (Indica vs Sativa)
THC for Night (How much?  what dose? AND in what form?  Chewables?, Oil (is oil smoked or put into food?) other??? I know we'll probably have to play with this a bit, but is there a range to start with?  Also, should it be the Indica/Setiva combo or separate out Indika (just use that) or Just Setiva?  

CBD:  How much, what dose? What dose range? Chewables? oil? other ???  Especially for someone who is working all day and wants to maintain high functionality, focused thinking, good memory, good concentration?  

Best research literature on these topics that you recommend?  Please send links :-)


This Quote seems perfect for all my questions today:

"Perhaps the secret of living well is not in having all the answers but in pursuing unanswerable questions in good company."    Rachel Naomi Remen

Thank You fellow bloggers for your Good Company on this Journey.

Sending Love, Light and Healing to ALL.

Kelly

Levi's cocktail

Stephen, and dear blog visitors, I'd also be grateful if you could review my husband's not so extensive cocktail. Should I increase the dosages or should I add something to the list in your opinion? 

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/jouRNAl/PaperInformation.aspx?PaperID=23446 

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.

Sativex (THC + CBD) plus temozolomide for recurrent GBM

This was mentioned in the comments a while back (February), but I feel these findings are significant enough to have their own post.

The original press release by GW pharmaceuticals came out on February 7.

The data was also published for the 2017 ASCO conference (click here).

"Median survival in the placebo group was 369 days, and > 550 days in the CBD:THC treatment group (NS) and 1 year survival was 83% and 56% in the CBD:THC and placebo groups, respectively (p = 0.042). "  

Even with the small numbers of patients (12 patients in the Sativex + TMZ group, 9 patients in the placebo + TMZ group), the difference in survival at one year still managed to achieve statistical significance.

Sativex (nabiximols) is available in Canada and Europe. 

https://en.wikipedia.org/wiki/Nabiximols

Sativex dosage

Dear all,
We just got Sativex but are not certain about the dosage. Has anyone used it? how many puffs ? Shold there be dosage escalation? Thanks!