Exceptional Responders

https://www.npr.org/sections/health-shots/2018/06/27/623525504/what-can-cancer-specialists-learn-from-patients-who-beat-all-the-odds

Poliovirus (PVS-RIPO) phase 1 update

Thanks to Al Musella for bringing this to our attention.

https://virtualtrials.com/news3.cfm?item=6529  (Al's commentary)

https://www.nejm.org/doi/full/10.1056/NEJMoa1716435  (full study, HTML)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1716435   (PDF download)

Here, as in some other viral therapy/immune therapy trials, we're seeing a long tail of survivors, in this case 21% surviving to 2, 3, 4 and 5 years (all dose levels).  This is comparable to DNX-2401 phase 1 trial, where 20% survived at 3 years, or Toca 511 + FC (13% alive at 3 years, all dose levels).

The most intriguing part of the study is the observation that some of the patients had dramatic responses to chemotherapy (including lomustine) after treatment with the modified poliovirus.  The randomized phase 2 trial open now is testing poliovirus alone versus poliovirus + single course lomustine.

This trial is open and Duke, and soon to open at Massachusetts General, UCSF, and Boca Raton.

https://clinicaltrials.gov/ct2/show/NCT02986178

SurVaxM - Update

https://mimivax.com/wp-content/themes/JointsWP-master/assets/pdf/download.pdf

Experience with Avemar?

Has anyone had experience with Avemar (fermented wheat germ extract)?   I am concerned about its possible interactions with Keytruda and Tensirolimus, as well as with Warfarin.  Research and literature are limited (see https://www.mskcc.org/cancer-care/integrative-medicine/herbs/wheat-germ-extract), but it may be anti-angigogenic and promote apoptosis.  We are particularly interested because Avemar is also said to help increase RBC production. My husband's RBC is low and he is feeling very fatigued. 

Just for background - my husband was diagnosed in 2/2016 with giant cell unmethylated and IDH negative GBM in his left temporal lobe.  He never had SOC.  In addition to two resections and hyprofractionated radiation, his treatment initially included an immunotherapy trial for REGN2810.  Now he is on Keytruda and Tensirolimus infusions, 100 mg of daily Temodar, Celebrex, Prozac, Metformin and Optune.  His tumor and cognitive condition are stable and he is fit and strong.  His only problems are anemia and kidney function issues.

FUCOIDAN

Hi there everyone,

Has anyone used Fucoidan? It's a seaweed based extraction.

I am trying to build up my immune system before my next round of chemo and have heard this is a good product. However there are vast differences in the retail price and I would love some feedback from anyone who has knowledge of this product.

With thanks,

Geraldine

To go or not to go beyond the 6 chemo cycle mark?(3 cycles TMZ + 3 cycles TMZ+Lomustine)

Hi folks,

My mother is a glioblastoma patient who was diagnosed in Sep 2017(IDH1 -ve, methylated). She had a complete resection and has completed her radiation. Following the radiation, we did 3 cycles of temozolomide and the following two cycles were Lomustine(CCNU)+Temozolomide, since I stumbled upon a research that the combination of the two results in a significant improvement in life expectancy for methylated cancers.

https://www.ncbi.nlm.nih.gov/pubmed/19188676

However, since this research had 6 cycles of lomustine+temozolimde after the radiotherapy, I wish to ask if I should go beyond the total 6 cycle mark for my mom to do a total of 9 cycles of chemotherapy? Has somebody gone through a situation like mine and gone beyond six cycles of chemo with lomustine and temozolomide in their protocol? Does more chemo always mean better survival? I've heard from my fellow caregivers that an increase consumption of CCNU+TMZ has a risk of liver failiure and pneumonitis, how true is that? If it is, is there anything that we can do to reduce the risk and still do this combination for a total of 9 cycles to get the benefit this protocol gives?

Some context: My mom's last MRI 2 months back showed no growth, her health stays decent, she tolerates the chemo well and her platelet/WBC/Hb/RBC stay around 100k+, 2.5k-3k, 12 and 3.7-4 respectively even during the CCNU+Temozolomide combination.

My mom also takes these supplements: Curcumin(4-5 g/day), Boswellia(4000 mg/day), Keppra(1000 mg/day), Quercetin(3000 mg per day), Resveratrol(400 mg/day) Bromelain(700 mg/Day), Celebrex(600 mg/day), Green Tea(400 mg/day), Ashwagandha(500 mg/day), Metformin 1500 mg day, Doxycycline/Mebendezole, Fish Oil(3-4g/day) and is on a ketogenic diet

I would love to hear from you guys!

Cocktail review after 1 year

Dear community,

I'd like to revise my husband's cocktail after 1 year of doing this protocol. He is at 14.5 months from diagnosis and has just started his 12th cycle of TMZ and just got his 3rd excellent MRI saying that the main part of the thalamic tumor is barely visible at the moment (which was the bigger concern of the two tumor sites) and the frontal one is still non-enhancing. 

Although he is methylated, I attribute the good results to the cocktail approach or at least to the synergy between the chemo and the cocktail because the first MRI after radiochemotherapy showed progression and it couldn't be pseudo progression, at least not on the frontal site because only the thalamic site was involved in the treatment. 

We're reaching the 1 year mark of supplementation with the following: 

Fluoxetin 40 mg

Chloroquine phosphate (Delagil) 250 mg (he already stopped taking it)

DCA  500 mg 2 times a day for a patient who is sadly weighs only 55-58 kg these days

Silymarin 630 mg

Celebrex 400 mg

The rest of the meds were added later on gradually. 

In your opinion, is it good to stick to the cocktail if it's working because we don't know what elements are working or after a year would it be wiser to make some changes in the regimen to disturb the tumor?

Does it make sense to take Celebrex if there's no edema and we are 1 year from radiation therapy?

I'm thinking about replacing DCA with the ALA + HCC protocol. 

Sorry if it was discussed before but is LDN an antagonist to methadon? Can the ALA + HCC protocol be effective without LDN? Combining this protocol with ketogenic diet is not an option for us because he has a sweet tooth and these days his main calorie intake is from fruits and baked goods which makes me frustrated big time but I can't help it, he lost so much weight. 

I'm not sure if we can use 800 mg of ALA 2 times a day instead of RLA 800 mg 2 times a day or should we double the dose of ALA considering that ALA is just 50% RLA.   

What's the longest period of time that a patient can take DCA? My husband is on a fairly low dose although he noticed considerable neuropathy on several occasions when we ran out of methadone for one day. Since it has painkiller effects I suppose that the neuropathy is continuous but methadone may conceal DCA's side effects. So I suppose that after a year we should address this problem and make at least a longer break of DCA.

Since his seizure he is on 300 mg of valproate acid 3 times a day, too. Considering that it became a necessity to take an AED I see reason to maybe replace fluoxetine with LITHIUM and so he would be taking almost the whole CLOVA cocktail. He's been on cimetidine 800 mg since last Sept./Oct. I'd like to exclude olanzapine because I read terrible things about its side effects but this way he is already taking 3 of the 4 medicine of the CLOVA cocktail anyway. 

By the way, at first, he was prescribed the same amount of sodium valproate in the A&E but the NO changed it to valproate acid later on. I know that those two are in the same family but can be any difference between their tumor-fighting properties?

I read here an older comment that stated that a patient's NO advised against taking Silymarin and valproate together because valproate is metabolized by the liver and Silymarin flushes it out. Is it a true statement in your opinion? I'm not sure if we can keep that in the cocktail. 

Cimetidine: I suppose it's advisable to take it together with TMZ. In our case it will be 24 cycles if he can tolerate it on the long term. So should he continue it for an additional year?

If stopping with DCA, Celebrex, chloroquine, he will only take a few prescription drugs (metformin, fluoxetine or lithium, alfacalcidol, D,L methadone and of course the anticonvulsant) and it seems a bit scary that natural supplements will be predominant. 

Do you recommend to add anything to this list at this stage of the disease?

Thank you for your inputs in advance! I think I would be a complete nerve-wreck if this blog did not exist. 

metabolic therapies

Hello all,

I'm wondering if anyone has tried the Care Oncology Clinic protocol? They are now in the U.S. and I'm considering it as an additional therapy for my husband. I'm interested in hearing about potential side effects of the drugs, what neuro-oncologists had to say about it, etc. Also, he's currently on a hydroxicytrate/ALA combo and I'm wondering which metabolic treatment would be best/has better data. He's also doing a combination of TMZ/CCNU.

Another question-- his most recent MRI shows radiation necrosis. Is there data that shows any natural treatments that could help?

Thank you all!

Temozolomide + a dropper of curcumin for possible synergy?

Today we made the first dropper of curcumin. 150 mg of curcumin with 250ml of 0.9NaCl. The dropper lasted 2 hours. On this day, the dose of oral curcumin was 5x400 mg (Longvida, SLCP).

There are several reports of possible synergies between curcumin and temozolomide. Does it follow from these studies that a drip of curcumin, oral curcumin and temozolomide should be taken in such a schedule so that their concentrations in the blood are maximized at the same time?

2014 https://www.ncbi.nlm.nih.gov/pubmed/25050915
We demonstrated that CUM enhanced the therapeutic response to TMZ in U87MG glioblastoma by enhancing apoptosis... We demonstrated that CUM enhanced the therapeutic response to TMZ in U87MG glioblastoma by enhancing apoptosis.

2015 https://www.ncbi.nlm.nih.gov/pubmed/26239619
Combined curcumin and TMZ treatment significantly (P<0.05) inhibited U‑87 MG cell proliferation and induced apoptotic death, compared with each alone.

2015 https://www.ncbi.nlm.nih.gov/pubmed/25542083
Autophagy inhibition improves the efficacy of curcumin/temozolomide combination therapy in glioblastomas.

Soon we will have 5 days of temozolomide. I think about whether it will be useful if temozolomide is taken at the beginning of a 2-hour dropper of curcumin?

Sulforaphane - an easy and potentially very useful dietary / supplement adjuvant treatment

 Hi everyone,

I thought I'd post a little comment on Sulforaphane today, as I've been spending some time recently studying it, and I'm growing quite convinced that it's a very beneficial compound which continues to be largely underutilized considering the strengthening evidence (for cancer in general) and ease of use.

Sulforaphane is a phytochemical compound which can be sourced especially well from Broccoli (but also from other cruciferous vegetables like cabbage, brussel sprouts, kale etc.) which seems to have a wide range of direct and indirect anti-cancer effects. I'm not going to recap everything here, but the following general video is quite exhaustive for anyone interested in the details:

https://www.youtube.com/watch?v=zz4YVJ4aRfg

One additional effect items not covered in the video is on the immune system, where in-vitro evidence seems to suggest that Sulforaphane may also have very significant immunomodulatory effects (e.g. lowers MDSC population, lowers PD-L1, increases mature dendritic cells...) which could have possible implications for immunotherapy. See study:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493295/


Beyond the likely clinical effectiveness, an important merit of Sulforaphane is its general ease of use and strong bio-availability. Clinical evidence suggests that it is easily absorbed, and is thought to cross the BBB (at least in small quantities, based on animal studies). Sulforaphane can be easily used effectively in a variety of ways, as long as the phytochemical interactions are respected.

To produce Sulforaphane, basically an element in the plant called Glucosinolates needs to mix with an enzyme called Myrosinase (this usually happens when chewing, chopping, etc), which is however rather heat sensitive and therefore easily destroyed in a high temperature cooking process. As a consequence, the vegetables are best consumed raw or lightly heated / steamed. Myrosinase is also usually destroyed in the blanching process when mature Broccoli is frozen. So as you can see, it's possible to consume a lot of Broccoli (e.g. frozen, cooked...) without getting much Sulforaphane benefit at all...

Optimizing Sulforaphane production can get quite complicated, but the below gives some idea how to get a fairly good amount:

Broccoli seeds & sprouts
These have up to 100x the Glucosinolates content of mature Broccoli plants, so represent a much more efficient source of Sulforaphane. Seeds actually have the highest concentration (more than 4mg per gram of seeds), and can be crushed and consumed directly. However, most people sprout the seeds 3-5 days, which is very easily and cheaply done at home using a sprouting jar. Ca. 100g sprouts will yield 40mg+ of Sulforaphane. Studies indicate that freezing the sprouts before using them will enhance Sulforaphane content by an average of 1.8x. If you want to go all the way to max the output, heating the the sprouts at 70C for 10 minutes will provide a further significant boost to usable Sulforaphane.

Mature broccoli
As mentioned before, it's important not to cook the Broccoli as the Myrosinase will get destroyed and no Sulforaphane will be produced. Broccoli should be lightly steamed max. 3-4 minutes. Also, frozen broccoli should be avoided as the blanching process eliminates the Myrosinase. If you have frozen Broccoli or plan to cook the Broccoli, then an alternative method to maintain Sulforaphane output is to mix the Broccoli with some Daikon Radish or mustard seed powder after cooking - both of these also carry Myrosinase, which can be used to make up for the enzyme lost in the cooking process.

Supplements
An increasing number coming to market. Important here is that the supplement provides either finished Sulforaphane OR Glucosinalate + Myrosinase. Glucosinalates without the Myrosinase will not be converted into Sulforaphane, as explained above. Studies have shown a strong synergy combining supplements with actual sprouts, leading to 2x+ serum levels of Sulforaphane.
For some reason, I'm finding much stronger Sulforaphane supplements (e.g.40-50mg) in Germany than internationally, not sure why. Examples:

https://www.amazon.de/Sulforaphan-Hochdosierte-Brokkoli-Extrakt-Kapseln-Magnesiumstearat/dp/B07663XZL2/ref=sr_1_5?ie=UTF8&qid=1528199244&sr=8-5&keywords=sulforaphane

https://www.amazon.de/Nutri-Store-Sulforaphan-vegetarisch-120/dp/B0047BU8GE/ref=sr_1_6?ie=UTF8&qid=1528199244&sr=8-6&keywords=sulforaphane

https://hk.iherb.com/pr/Jarrow-Formulas-BroccoMax-Myrosinase-Activated-60-Veggie-Caps/4297

https://hk.iherb.com/pr/Source-Naturals-Broccoli-Sprouts-Extract-60-Tablets/2456


A note on dosage: optimal dosage is not known, but many studies (showing effect) have used ca. 40mg-90mg of Sulforaphane daily. However, I think there is fairly little toxicity risk of going too high, so in my case I'm taking around 100mg+ bid (sprouts + supplements), without any problems so far.


I hope this is helpful maybe to some of you. Good luck everyone!

John

Boldine

Hi again.  Does anyone know anything about Boldine? Can't seem to find much for it on the internets. Is this available anywhere as an ingredient for a cocktail? Read a report from Invest New Drugs (2009) 27:517–525 DOI 10.1007/s10637-008-9203-7

Boldine: a potential new antiproliferative drug against glioma cell lines
Daniéli Gerhardt & Ana Paula Horn &
Mariana Maier Gaelzer & Rudimar Luiz Frozza &
Andrés Delgado-Cañedo & Alessandra Luiza Pelegrini &
Amélia T. Henriques & Guido Lenz & Christianne Salbego

from 2008 which looks quite interesting.

First results of cocktail trial (memantine, metformin, mefloquine, temozolomide)

I'll be working on a review of the latest brain tumor news coming from the ASCO conference currently underway.  Since this is the brain tumor cocktails blog, thought I'd post these results to start off.

Phase I factorial study of temozolomide plus memantine, mefloquine, and metformin as post-radiation adjuvant therapy for newly diagnosed glioblastoma.
https://meetinglibrary.asco.org/record/164026/abstract

The abstract gives maximum tolerated doses for doublet therapy (TMZ + one of the other drugs), triplet, and quadruplet combinations.

2 year survival rate for the entire trial population (all combintions) was 43%, similar to the 2-year survival seen in the EF-14 trial for the Optune + TMZ arm.

Since some of the combinations were probably more effective than others, it will be interesting to see the results when separated by treatment arm.

gene sequencing

Dear All,

I have likely a difficult and too general question. We have a possibility to perform gene sequencing on the  Illumina HiSeq 1500  platform.  Could you please advise and share information which mutations may/should be tested to provide options for the GBM treatment  besides the standard path (radioteraphy+TMZ and TMZ after that).

Many thanks.