Tuesday, 14 August 2018

GBM diagnosed Sept 2017, options in the UK/ Europe

Hi Stephen
I'd be very grateful for your guidance.

My husband 55 was diagnosed with GBM Sept 2017
Only symptom lost left peripheral vision and 'pepper smells'
Neuro-oncologist said it was a very large tumour and Joe had been able to adapt to very well without any major symptoms until now...

GBM right temporal&frontal&close to right MCA
Partial debaulking temporal lobe

Usual chemo/radio 6week treatment
Usual chemo 6cycle treatment

Joe had a major stroke close to GBM area, after cycle5 so treatment stopped.
At stroke unit last 8 weeks.
Much better and left side paralysis improved.

Currently on:
Keppra 500mg x2
Clopidogrel 75mg alternate days
DEX 16mg/day 02 Aug
12mg/day 09 Aug
**Stroke dr put him on DEX to see if might improve his movement.
Oncologist said OK to try...
It hasn't made any noticeable difference.
They're weaning off DEX by 4mg/week.
I'd like to reduce faster safely to avoid too much DEX build-up in body. 

Recently, Oncologist said last MRI seems to show new growth according to Prof NeuroRadio however surgeon at meeting is not so sure and suggests MRI shows damage from stroke/treatment?
Oncologist says he has nothing more to offer so now we are on our own.

We would be very grateful for your recommendations please.
We live in LondonUK/Portugal and have family connections to Drs/Pharmacists in Portugal should you recommend anything that might be harder to source.

I found your website following an article I was reading re Ben Williams.

We worked so hard to retire in our 50s and now we're ready, we both get hit by cancer... but we're strong and positive and won't give up! 
Tiredness makes it hard for us to do the necessary research needed...

Please can you give us suggestions of what you would recommend might be the best protocol for my husband to follow?

Many thanks,
Jane

Following on from my post sent moments ago about Joe's GBM I forgot to add:
MGMT unmethylated
IDH1 no mutation
ATRX likely retained

Your husband's oncologist appears to have a limited toolkit if he's not able to offer any salvage therapy.

If true progression is confirmed, and you're able to travel, the following European trials are interesting:

https://clinicaltrials.gov/ct2/show/NCT03294486 (this is a French trial, and not dissimilar in principle to the Tocagen therapy offered in North America, Toca511+ FC)

https://clinicaltrials.gov/ct2/show/NCT02866747 (also in France, a trial of hypofractionated radiation with or without immune checkpoint inhibitor durvalumab)

There are trials recruiting in the UK and Spain for EGFR-directed antibody-drug congjugates, if his tumor if his tumor is positive for EGFR amplification (was this tested?).

There are also trials in the UK and Spain with immune checkpoint inhibitors for advanced solid tumors. Of all these trials I like the first one mentioned above the best (the oncolytic virus/gene therapy trial in France).

Do you have any other pathology information beyond the MGMT, IDH1 and ATRX results?

Hi Stephen,
Thanks so much for your quick and considered response.

I am totally ignorant regarding trials and bit anxious..
Is your preferred trial the first of its kind on humans or does it have evidence of success?
Statistically relevant?...
Please forgive my ignorance..

Joe's oncologist has tried various options with other patients, but is reluctant to offer anything for Joe.
When I queried about possible immunotherapy, he replied it could cause terrible diarrhoea and that Joe wasn't fit enough to do it?
He said he could suffer terribly, lose 10kg and he's not happy to do it to someone as sick as Joe...?

Joe's not underweight for his height, but maybe he is referring to his recent stroke and left side partial paralysis?
I will enquire about this again..

He said he could offer Bendamustine to Joe but that he doesn't really like it.
He said he's tired of giving standard care and it not working and that he's pushing forward to change this in near future.

This is his profile which I think looks quite impressive? www.uclh.nhs.uk/OurServices/Consultants/Pages/DrPaulMulholland.aspx

I will ask oncologist if there is any more pathology test results for Joe.
Which pathology tests would you recommend I ask Joe's oncologist please?

Also, do you recommend Joe follows any
Repurposed drugs like Prof Williams?
Or supplements?

Many thanks, I'm very grateful for your time and support
Jane

Saturday, 11 August 2018

What cocktail should we start with?

Hello everybody!

My mom was operated for a brain tumour and diagnosed with GBM on July 24th. She is scheduled to start radiation and chemo on August 14th.

Ever since the diagnosis I've been researching continuously. There is too much information to process in such a short amount of time so I come to you for help...

I am trying to put together a startup cocktail that will work best with radiotherapy. So I'm looking to first add items:
  • that have been proven to be most effective. I can add the ones that are less effective later.
  • that are relatively easy to access in Romania or the EU.
Thank you and best wishes to you all.

Report on the treatment of 15 patients in the IOZK clinic.

The IOZK clinic in July 2018 published an article with information on the treatment of 15 patients.
Some of the details seemed interesting to me.

The first 10 patients (in the table) were treated using vaccines based on dendritic cells:
- Of these, 3 patients survived 18, 22 and 10 months. By the way, the patient, who survived 18 months, used the CUSP9 protocol.
- The remaining 7 patients continue treatment. However, of these 7 patients with no progression, only 2, with a result of 27 and 17 months without progression after surgery. In others, the tumor slowly progresses.

Also, we see that 3 patients out of 15 used perillol alcohol (POH).

http://www.iozk.de/aktuelles/iozk_glioblastoma_immunotherapy_austin_oncology_report_2018.pdf

"The median PFS was 13 months. Median OS was not reached with a median follow up of 17
months (rang 4-30 months). Estimated overall survival at 30 months was 58%..."
"DC vaccinations have been given after the chemotherapy. The obvious reason is that temozolomide might affect T cell proliferation and hence the anti-tumoral immune response upon DC vaccination."
Does this mean that it is better not to combine the Stupp protocol with the DC vaccine in the same period?


Friday, 10 August 2018

newly diagnoised with GBM

Dear stephen,thanks for adding me to the blog. This blog is very informative for me.I am from IRAN and I has been recently diagnosed with GBM.I have not had a biopsy or surgery yet.But I am in the list of hospital and they will call me for operation during this month.My neurosurgeon is so skilled and told me it is a GBM-multifocal tumor.I have some questions.
1. I am about to have a surgery,what should I do before that to get best result of surgery?
2. I have planned for a cocktail:
-verapamil ,3 days before chemo,during chemo days and 3 days after chemo.
-melatonin daily at bedtime.
-tamoxifen 
-hydroxy chloroquine sulfate
-accutane
-cimetidine
-celebrex
-aspirin
-and some supplements like vitamin D3, curcumin,selenium and...

I have some question about my plan:
  • how should I put them in 4 bunches?for example in the morning I have a bunch,for lunch I have a bunch and also for dinner and bedtime.
  • Are these all drugs for just chemo cycles?which of them can be used during radiotherapy?
  • which drugs should be continued after chemo and radiotherapy?
  • I have a problematic issue in my plan.I want tamoxifen and also cimetidine.But there is a severe interaction between them.How can I solve this problem.
  • Is my plan good at all?any suggestion is appreciated.thanks all of you.

Sunday, 5 August 2018

R-lipoic acid

That was discussed in previous posts, but I am still confused.

In the paper by Schwarz et al http://crescopublications.org/pdf/crooa/CROOA-2-019.pdf they write on the following treatment

Unless specified the metabolic treatment was: i) 800 mg lipoic acid bid(Solgar, Leonia, NJ, USA)500 mg HCA tid (Solgar); and5 mg naltrexone (Revia; Bristol-Myers Squibb, Rueil-Malmaison, France) at bed time.

But I could not find any product with the R-lipoic acid by Solgar. Also,  for Patient 6, they write

She was treated with α-LA (600mg), 500 mgHCA i.v.tid and low-dose naltrexone.

but, for instance, for Patient 9

In early March 2013, this started 2g sodium R lipoate per day, as well as 500 mg HCA, 3 times per day.

that suggest R-lipoic form.

Does it mean that the form of ALA has been different? I am not sure which form of ALA should be preferred.

Friday, 3 August 2018

This just in:

medpagetoday.com

ASCO Reading Room | Addition of a Personalized Vaccine to Standard Therapy in Glioblastoma

 

Thursday, 2 August 2018

What to add to Irinotecan + Avastin

Hi everyone,

I have a few questions I was hoping I could get some opinions on. My husband is receiving treatment for his second GBM recurrence-- currently on irinotecan and Avastin. I'm feeling unsure of what I can combine with this and I have a few specific questions:

- Is it safe to add Accutane? I have read on this blog that it could affect chemotherapy treatment but is that still the case with irinotecan since it uses a different mechanism?

- Would it be wise to consult with his doctor about adding the ALA-hydroxycitrate-naltrexone  treatment in addition to this?

- At what point do you change up additional treatments or supplements? He was using POH with a nebulizer but we stopped that after progression and I'm just not sure if we should continue it. Same with other supplements and prescriptions he has been taking. For instance, I'm not sure if he should continue taking metformin or if he should up the dose? (currently 500mg twice a day).

I'd be interested to hear anyone's experience with irinotecan/Avastin. So far, he's tolerated it well and it has improved a number of his symptoms but he has experienced some confusion and he will be getting an MRI soon. I'm desperately seeking clinical trials that he might qualify for but between the Avastin treatment, his speech issues and the fact that he'd technically be on his third recurrence by the time he's even eligible for a trial, our options for anything promising are incredibly limited. His doctors have told me that a vaccine type of therapy might be the most effective. I'm considering IOZK after reading some posts about it here and doing some research.

My husband is 32, we have two young kids and I fear that we are quickly running out of options. Thank you again to all who share here!

Abby

Tuesday, 24 July 2018

Herbal remedies for brain tumors?

Hello,

I was recently diagnosed with a low grade (grade 2) diffuse, infiltrating astrocytoma.  I am probably in the best situation possible (male <35 years of age), the tumor was in my right frontal lobe and not near anything critical, the neurosurgeon was able to achieve a total general resection with no deficits or complications after surgery.

However, after reading through some literature I became intrigued by this paper on herbal therapies for patients with poor prognosis brain tumors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809810/ which seems to have helped a few patients that had a much worse prognosis than I do.  

I was curious to know if anyone on the forum has come across this paper or tried similar herbal remedies?  My main concerns are: 
  1. I don't know how to evaluate whether or not the authors are reputable or qualified for this kind of research, does anyone have any insight on how to do so?  I know the study is not meeting the standard for a true medical trial since there is no control group, etc. but I'm willing to give it a try if at least the authors/source of information is somewhat reputable. 
  2. Getting the herbal remedy right, I did reach out to the author and they are willing to ship their herbal remedies to the US for a fee and they recommend taking the treatment continuously for ~1 year based on their ongoing research.
  3. I'm not sure if anyone has tried similar herbal remedies with any success? 
If you could answer any of my questions it would be great.  Please do reply to this post if you can. 

Thanks! and of course, wishing you health and happiness. 

Monday, 23 July 2018

Right to Try (for U.S. patients/advocates)

Hi guys,

I'm wondering if anyone here has pursued the Right to Try law here in the United States? Searching the blog, I couldn't find anything...

My brother is living in Texas where the law has been passed and I've obtained the document provided by the organization website to present to his doctors. (The document is linked here under "How do I initiate a request?" or here is a Google Doc version I uploaded which is the exact same)

James would like to try DCVax-L, if possible.

In order to produce the DCVax-L vaccine, you need to supply fresh or preserved tumor tissue. I've contacted the drug company, Northwest Biotherapeutics https://www.nwbio.com/) and was told:

"In order to manufacture DCVax-L, we usually require 2-3 grams of frozen tumor tissue, although we have worked with less in certain circumstances.  The tissue must be stored frozen without any chemicals or preservatives and not in saline or blocks of paraffin."

I've confirmed that the tissue from his previous resection has now been transferred to paraffin so is unusable.

James's doctors have already said another resection is not advisable due to the location of his tumor progression. However, assuming we could get a biopsy to have some fresh tissue, I'm wondering if this would be a block for his doctors to go ahead and pursue the Right to Try submission to the drug company.

Would they be likely to submit the document and start the legal process if we don't even have the tissue?

It would seem foolish to do a biopsy if we weren't for sure going to be a candidate for the vaccine.

(Again, I'm unsure if a biopsy is possible at the moment but should find out this week.)

Additionally, I requested more information from NWBio about the Right to Try law and she didn't address it with detail, but just assured me that without tissue, nothing could be done.

Does anyone here have experience with kickstarting this Right to Try process? Any tips or advice would be much appreciated.

Link to my first post outlining James's current condition for context.

Thursday, 19 July 2018

The trembling of the hands and the change in facial expressions when falling asleep

My mom's hands are moving and her facial expressions change when she falls asleep and sometimes in a dream. She does not remember this. It looks a little scary.

Half a year my mother took valproic acid (Depakin) 500mg a day. However, a month ago an electroencephalogram showed the absence of an epileptic activity and we stopped taking it. Perhaps, the trembling of the hands and facial expressions when falling asleep increased.

What could this mean?

Wednesday, 18 July 2018

Fungal lung infection (cryptococcus) - anyone had this?

My husband was diagnosed with a fungal lung infection that's supposedly common for immunocompromised patients...but I've not seen much mention of it in conjunction with GBM.  In some cases, the fungus can enter the brain via cerebrospinal fluid, possibly leading to meningitis. 

The prescribed medication for the non-CSF version is a six month course of Fluconazole, which can impact liver function.  I'm guessing this may mean our NO won't proceed with additional 5/23 cycles (cycle 3 just completed, will hear about the MRI on Thursday), but the NO and the infectious diseases physician are still trying to figure out how to proceed.  Anyone have experience with this set of circumstances?

Seeking Update on Experiences with Dendritic Personalized Vaccines in Germany

I have begun researching personalized dendritic vaccines in Germany and have found several clinics which offer them (some from this blog). I would be incredibly grateful if people would share/update their experience with dendritic vaccines. In particular, I am hoping to learn:

Which clinic you or your loved one sought treatment at?
What stage of illness you sought treatment (post-surgery, post-recurrence)?
Whether treatment was effective and if so for how long?
What the clinic used to produce the vaccine (fresh sample, paraffin sample, blood sample, etc...) .

Clinics I have begun looking into include: IOZK, Unifontis/Dr. Drevs, Hallwang, NextGen Oncology, CeGat and Praxisgemeinschaft/Dr. Nesselhut.

I am seeking treatment for my husband who is 53 yo. We live in the U.S. and have 2 children. This is my first time posting and I want to express my immense gratitude to all who have posted. It has been an incredibly helpful and sustaining resource. My heartfelt compassion to all of you.

Tuesday, 17 July 2018

Lomustine Side Effects

Hello everyone,

New here, but have been reading since last Februrary when my brother, James (33 at diagnosis, 34 now, married with 3 kids under 6), was diagnosed with Stage 4 GBM. He had a full resection in March of 2017 at UT Southwestern in Dallas and had the standard of care with TMZ + radiation. He also followed a loose ketogenic diet and was doing some supplementation then (I'm not quite sure what - we don't live in the same state so my mom is our "middle man" in communicating everything to me!). He then enrolled in a clinical trial to receive Nivolumab in combination with chemo.

James tolerated this treatment well in terms of side effects, but was kicked out of the trial when he showed regrowth.

His doctors recommended to put him on Lomustine. He was nervous about the possibility for severe lung side effects and decided to forgo taking this chemo (this was a few months ago). He took a trip to Italy with his wife, ate what he wanted and really had a good time.

Upon return, his next MRI showed aggressive growth and growth in what was once a "spot" but now is clearly a tumor. Additionally, it is growing toward the "midbrain" so his doctor said another surgery was probably not going to be a future option. This was in June of this year. His doctors were also pretty upset that he'd chosen not to take the chemo. My brother did not communicate this with them, so I know that was part of the frustration and I'm wondering how this has impacted (if at all) their attitude toward James as a patient.

I was fortunately able to attend this appointment with him and the doctors were pretty upset to begin with. I also brought a list of questions based on the PDF Ben Williams and Stephen have created/maintained. They answered all of my questions, but I think they may have assumed James didn't go through with Lomustine for the first time because we read the book - which is not the case. Anyway, I got an odd vibe from both doctors after asking my list of questions...

After this appointment, James decided he would take Lomustine. His doctors also said they could and would combine it with Nivolumab, but due to some process of insurance having to deny it twice before they could get it, he has not received an infusion of that yet with the chemo. Their plan is to do this on his next appointment and with his second round of Lomustine. His next appointment is next week, I believe.

Sorry that was a long intro...

Now for my question: can any of you share with me your experience of side effects with Lomustine? James took his first pill on June 25. Since then his state has been:

  • bedridden for the majority of the time
  • vomiting/nausea (he's taking Zofran for this)
  • mobility of his right side is worsening all the time. He cannot move his right arm/hand. He picks it up with his left hand to move it around. My suspicion is this has to do with too high of a dose of DCA after reading more here. He stopped taking that just a few days ago.
  • difficulty walking - now uses a wheelchair
  • headaches
  • cannot speak very much or very well
  • difficulty opening eyes
Now, there are times when he is NOT like this and has energy, but the majority of the time since taking his first chemo pill, his side effects have been what I've listed above.

Is this normal?

My mom has reached out to the doctors and they ordered him to get blood tests done. After those were submit, they never replied with anything regarding his symptoms. I'm curious if this has anything to do with what the doctors think of my brother's future or if there are communication problems (maybe a bit of both).

I would really appreciate some insight into what you all have experienced with this chemo. I've read through a few posts and am trying to discern if his symptoms are side effects or if something worse is going on.

Thank you!

Wednesday, 11 July 2018

Gliosarcoma early recurrence?

I am mostly reader of this blog,  and I found many useful information and hope. Simultaneously, I tried to be as anonymous, as it is possible. Sometimes I afraid to even name the beast we face.

But now our situation looks dramatic and I seek help and additional information.

The short story: a young adult, diagnosed almost one year ago with a front lobe tumor (gliosarcoma). There were no prior symptoms, only sleepiness prior to a major seizure.

After double surgery at the end of July 2017, we spent a month recovering from complications. Next, our doctor administered irinotecan+carboplatinum. After 2 cycles of the chemo, we passed through 6-weeks radioteraphy with maximal possible doeses and TMZ administered daily. Next, from December: once cycle of TMZ and 3 cycles of TMZ+CCNU. MRI's at the early January and at the middle of April indicated stabilization.

Unfortunately, MRI at the end of June reveals contrast enhancement and a new diffused area outside the primary site.  Our doctors say its most likely non-resectable recurrence and or progression, and they changed the chemo to a new combo (topotecan and dacarbozine). I have asked, whether it could be a pseudo-progression, due to radiotherapy, but they exclude that.

Since December, when I discovered this blog and the Ben's book, we introduced some supplementation, including PSK/grifolan, bee-honey products, curcumin, berberine, fish oil, boswellia, 5-10 mg of melatonin, syllimarin. I was very afraid of including any of ``the regular drugs'' in coctails mentioned here.

The current neurological status of the patient is essentially stable and reasonably good, and we did not notice any particular symptomps indicating the progression.

I seek for any information, whether the new drugs could be supported by the coctail approach, and perhaps there are persons who have undergone a similar treatment. I am thinking on a few most frequent drugs (CQ, metformin, celebrex, melatonin in high doses), as well as POH.  Unfortunately, we have no information on the genetic status of the disease.

I would be also very grateful for your advice and/or information on clinical trails in Europe, we live in Poland and US/Canada are likely non-available for us.

Repurposing drugs for GBM

I think it's a very recent review paper, which you may find interesting
https://www.sciencedirect.com/science/article/pii/S0304383518303124?via%3Dihub

Abstract: Glioblastoma multiforme is the most common, aggressive and lethal type of brain tumor. It is a stage IV cancer disease with a poor prognosis, as the current therapeutic options (surgery, radiotherapy and chemotherapy) are not able to eradicate tumor cells. The approach to treat glioblastoma has not suffered major changes over the last decade and temozolomide (TMZ) remains the mainstay for chemotherapy. However, resistance mechanisms to TMZ and other chemotherapeutic agents are becoming more frequent. The lack of effective options is a reality that may be counterbalanced by repositioning known and commonly used drugs for other diseases. This approach takes into conside ration the available pharmacokinetic, pharmacodynamic, toxicity and safety data, and allows a much faster and less expensive drug and product development process. In this review, an extensive literature search is conducted aiming to list drugs with repurposing usage, based on their preferential damage in glioblastoma cells through various mechanisms. Some of these drugs have already entered clinical trials, exhibiting favorable outcomes, which sparks their potential application in glioblastoma treatment.
 
Unfortunately, this article is not open access.
 

Monday, 9 July 2018

Optune - sensitivity to conductive hydrogels - what to do?

Hello,

My Father suffering from redness and itching that make from the op-tune conductive hydrogels

We Cant find any solution for this, and this is very frustration problem?.. anyone has any idea or tip how to win this battle against  the crazy 
itching and red wounds?

Thanks!




Saturday, 7 July 2018

Perampanel for uncontrollable seizures and tumor volume reduction

New study:  Seizures and Tumor Progression in Glioma Patients with Uncontrollable Epilepsy Treated with Perampanel.

https://www.ncbi.nlm.nih.gov/pubmed/29970574  (abstract only)

http://sci-hub.tw/10.21873/anticanres.12737  (PDF download from sci-hub)


"Obvious seizure control was observed in 10 analyzed patients (100%) and 6 patients (60%) became seizure-free"

"Tumor volume and peritumoral edema within 6 months were volumetrically analyzed by MRI-FLAIR images, and the volume changes were evaluated. The tumor volume decreased in eight of 9 patients during 6 months by FLAIR image (Figure 2) and increased in one (Case 9) of 9 patients"


See also

Seizure response to perampanel in drug-resistant epilepsy with gliomas: early observations

https://www.ncbi.nlm.nih.gov/pubmed/28492978

Tuesday, 26 June 2018

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

Saturday, 16 June 2018

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.

Wednesday, 13 June 2018

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

Sunday, 10 June 2018

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.

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!

Thursday, 7 June 2018

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. 

Wednesday, 6 June 2018

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?

Tuesday, 5 June 2018

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







Sunday, 3 June 2018

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.

Saturday, 2 June 2018

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.

Friday, 1 June 2018

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.

Thursday, 31 May 2018

Bioavailability of WokVel Boswellia Serrata vs "ordinary" Boswellia Serrata?

Hi all,

I've read here that WokVel boswellia serrata has greater bioavailability than the "usual" boswellia formulation.  But I've not been able to find anything in the medical literature or on the WokVel website confirming this.  If I could replace the canonical dose of 4200 mg H15 BS/day with a smaller number of WokVel pills (what's listed on the supplements spreadsheet as three 333 mg WokVel capsules/day), that would make my husband really happy.  Anyone have any insight or citations to offer?

I did contact the WokVel company but they're oriented towards the business end, not end consumers, and my inquiry just resulted in an email asking about my business plans.

Tuesday, 29 May 2018

Tagrisso ?

Hello, first post here, from the husband of a dear wife recently diagnosed with a Grade IV glioblastoma.  Red flags at a UCLA Urgent Care led to a ct scan followed by an MRI and admission.  Complete resection was performed 30 hours later. She followed up with radiochem, and is now in her second course of adjuvant Temodar. We were approved for Optune and are now two weeks in with that, holding firm at about 95% compliance and are also madly ingesting basically everything in the "A" list from the list in the library, thanks to a lot of wonderful help from Mike B here.

Anyway, our doctor suggested we might benefit from a drug called Tagrisso, from AstraZeneca Medicines.  Don't see anything about that in the stacks so far, so was wondering if anyone has any thoughts regarding it. It's proven to be an efficacious treatment for lung cancer but could have crossover value since apparantly it crosses the BBB. 

Hopefully human clinical trials won't be too far down the road...

I love out of the box thinking when fighting GBM.

New therapeutic technology that uses Zika virus strains to treat Glioblastoma  -- https://www.zikazoom.com/zika-science/washu-innovates-drs-milan-chheda-michael-diamond/#comment-5324

DCVax Update


https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1507-6

Mike B

Friday, 18 May 2018

HSPPC-96 vaccine Phase 1 trial results in China

Heat shock protein peptide complex-96 vaccination for newly diagnosed glioblastoma:
a phase I, single-arm trial
https://insight.jci.org/articles/view/99145   (open access)

The survival results of this trial are worth remarking upon.

20 newly diagnosed GBM patients received standard treatments plus HSPPC-96 vaccine (also known as Prophage, under development in the USA by Agenus). All had total tumor resections, and the majority had MGMT unmethylated tumors and were IDH1 wild-type.

19 of the 20 were evaluable for efficacy. Median survival for the entire group was 31.4 months.  I've seen only a couple of other small trials (vaccine trials involving complete or near complete tumor resection) with efficacy outcomes comparable to this.

Clear efficacy of the vaccine was shown by tumor specific immune responses (TSIR) being increased on average by 2.3-fold after vaccination, and the fact that those with "high" TSIR (TSIR above the median) had not reached median survival (> 40.5 months), while those with low TSIR (below the median) had median survival of only 14.6 months, showing vaccine efficacy in only a subset of patients.  Median PFS are unremarkable (11 months median for the entire group, 12.3 months for the high TSIR group), but immune-related pseudoprogression could have been a factor in dropping PFS values.

Compared to the phase 2 trial published by Bloch et al. in 2017,  https://www.ncbi.nlm.nih.gov/pubmed/28193626
the Chinese trial had worse PFS outcomes but better survival outcomes, also suggesting that pseudoprogression may have been a factor in the Chinese trial.

Additionally, patients with MGMT-methylatated tumors had far better outcomes in the Bloch et al. trial, but in this Chinese trial, 14 out of 16 tested tumors were MGMT unmethylated.

A trial is currently underway testing pembrolizumab with or without HSPPC-96 vaccine, and I would expect the combination therapy  to improve even further on the efficacy results of the vaccine.
https://clinicaltrials.gov/ct2/show/NCT03018288


Saturday, 12 May 2018

PSK and curcumin source in Europe

Dear All,

probably the subject has been discussed many times, but could you please recommend a source of  PSK and curcumin (also other coctail supplements) available in Europe? I live in Poland.

For PSK, besides Oriveda, I found  https://www.mycomedica.cz/ They explain that the products are sold as "veterinary" due to absurd EU regulations, but they are apparently available across the country, so I suppose that the quality is decent.

As for Curcumin Longvida, I found only

https://www.amazon.de/Longvida-Hochdosiert-Curcuma-Bioverf%C3%BCgbarkeit-Monatspackung/dp/B01NCTQFL8/ref=sr_1_1?ie=UTF8&qid=1526164318&sr=8-1&keywords=curcumin+longvida

https://www.amazon.de/Curcumin-LongvidaTM-500mg-Kapseln-Nutrivene/dp/B003D0A8Q0/ref=sr_1_4?ie=UTF8&qid=1526164362&sr=8-4&keywords=curcumin+longvida&dpID=41nYzvUsCZL&preST=_SY300_QL70_&dpSrc=srch

both of which are rather expensive,  and also

https://pl.iherb.com/pr/Now-Foods-CurcuBrain-Cognitive-Support-400-mg-50-Veg-Capsules/57292

However, my primary concern is quality and safety of these products. Would you please recommend other sellers or product in this group?

Many thanks.

Stefan