Friday, 31 August 2018

ERC1671 vaccine randomized phase 2 trial results

Phase II study of ERC1671 plus bevacizumab versus bevacizumab plus placebo in recurrent glioblastoma: interim results and correlations with CD4+ T-lymphocyte counts.

Median overall survival (OS) of patients treated with ERC1671 plus bevacizumab was 12 months. In the placebo plus bevacizumab group, median OS was 7.5 months. The maximal CD4+ T-lymphocyte count correlated with OS in the ERC1671 but not in the placebo group.

CONCLUSION:

The addition of ERC1671/GM-CSF/cyclophosphamide to bevacizumab resulted in a clinically meaningful survival benefit with minimal additional toxicity.

Tuesday, 28 August 2018

I am trying to remember.  Was it posted at one point that Omega3 should not be taken during TMZ treatment?

Thank you.

Sunday, 26 August 2018

Alternative Treatments for GBM

My mother was sadly diagnosed with a glioblastoma in January of 2018. She underwent her "debulking" surgery a week later. This went well, with almost all of the tumour being removed. Unfortunately, a brain haemorrhage occured 2 days postop and she was left in her NHS hospital room for many hours before receiving any medical attention (despite repeated pleas from myself and another family member for a doctor to be brought).

She spent the next month bedbound, unable to feed herself, and was subsequently deemed unfit to receive the standard chemo/radiotherapy treatment; this was still refused even after she'd improved and regained some limited mobility.

7 months later, and a recent MRI shows that the tumour is starting to recur. Mum is slowly deteriorating.
The only treatment I have been able to obtain thus far are the "Care Oncology Clinic" drug cocktail medications and a number of nutritional supplements, chosen based on research I've read online.

I know lots of good information has already been posted on this blog and elsewhere regarding alternative treatments for GBM, but since mum still cannot access the standard treatment, apparently because of her poor performance status, I'm interested in hearing other people's experiences with any of these alternatives.
Examples would include clomipramine, CUSP9, cannabis oil, immunotherapy, ketogenic diets and the Optune device, but we are interested in anything that may help.

I would love to see this damn tumour shrink on the next MRI.

Thanks.

Saturday, 25 August 2018

SPINAL METASTASIS OF GLIOBLASTOMA

Does anyone have any recommendations for spinal 'drop metastasis'?

In addition to getting the bad news that my husband's tumor is progressing, we learned yesterday that his recent 'foot drop' and increasing foot numbness is most likely the result of a rare occurrence called  spinal metastasis, whereby glioblastoma cells travel through the spinal fluid and drop to the bottom of the spinal chord.  The was a small area of enhancement seen on an MRI he had done on Thursday of this week.

We have an appointment with our radiation oncologist on Tuesday.  The proposed treatment for this condition will be to radiate that spot on his spine.

I wonder if anyone else her has experienced this condition.  I worry that radiation will cause further damage.

My husband's full history can be found here:
https://btcocktails.blogspot.com/2018/08/here-is-detailed-timeline-of-my.html

Thank you in advance for your help!

Ashley

Thursday, 23 August 2018

Avastin Considerations

Hello All and thank you in advance for your excellent advice.  It has been helpful over the years and hopefully, it will continue.  Over 3 years since my 1st resection of GBM and a couple of resections since with the latest this last June.

I have been taking Keytruda since before and after my last resection..  Now today's MRI is showing a large swelling in the brain but I am not having any symptoms.  No headaches or other effects.  My NO wants to administer Advastin to reduce the swelling and then determine new treatment options, either more TMZ, radiation, etc after the swelling is reduced.  there is one small potential tumor mass outside of the swelling area.

I would like thoughts on taking advastin to reduce swelling and potentially stopping more tumor growth. 

Thanks,

Marc

Wednesday, 22 August 2018

Mom's Cocktail (Updated)

My mom was diagnosed with GBM, had a resection, and this is her treatment while on radiation/chemo.

Age 62
Weight 87 kg (191.8 lbs)
Height 176 cm (5 feet 9 inches)


Radiotherapy Medication
Morning
Afternoon
Evening
Notes
Granisetron 1mg

1
1h before TMZ

​Sildenafil 50mg
1
1/2
With TMZ and Celebrex
Temozolomide 140mg
1
​1h before RT
Celebrex 200mg
1
1
Anti inflammatory 
Boswellia 400mg
3
4
4
Anti inflammatory 
Valproic Acid 500mg
2
​2
​Metformin 1000mg
1/2Lowers blood glucose
Omeprazole 20mg
1
​1
​Hidroxychloroquine 200mg
1
1
Not Chloroquine yet
Curcumin 500mg
2
2
2
Not Longvida yet
Melatonin 5mg

​4
​Probiotic
1
Multivitamin
1


​Alfacalcidol 0.5mcg
1
2
1
​Vitamin D 2000UI
1
1
​Selenium 200mcg
1
Sulforaphane 50mg
2
2
2
Maitake 650mg
1
1
THC vape
​1
1
30m before RT
CBD oil 10% drops
4
6
4
1h before RT
Omega 3 2000mg
1
1
MCT oil tablespoon
1

​For ketosis
Ketogenic diet & Intermittent Fasting


​First meal 3 PM (after RT)
Wim Hof MethodBreathing exercises 

We'll be adding the following as soon as we get the order in:

  • Berberin pure powder 1g/day
  • Ashwagandha 2g/day
  • Pterostilbene 250mg/day
Anything important we should add/change? Thank you guys!

Tuesday, 21 August 2018

Vaping Cannabis?

There is evidence that THC and CBD help with the treatment glioblastoma and other forms of brain cancer.

Usually it is administered in the form of oil: Rick Simson Oil or the product Sativex, that contain both cannabinoids. However, up to now I only managed to find CBD oil, and some high THC cannabis bud.

My question...

How should I best administer them? Does vaping the bud work just as well? (alongside the CBD oil).

Thanks.
Here is the detailed timeline of my husband's diagnosis with GBM.  I need help!

My husband is a 47-year old International Airline pilot who was in perfect health prior to his diagnosis in April.  After two surgical resections and 6 weeks of RT/TMZ, he is now taking daily TMZ on a metronomic schedule.

3/31/18 Presented with acute aphasia and vision loss, medevacked to Palmetto Richland hospital (Columbia, SC) tumor was discovered in left temporal lobe

MRI (missing report details)
4/2/2018TRANSPORTED TO MUSC, CHARLESTON, SC
4/4/2018SUBTOTAL RESECTION OF LEFT TEMPORAL MASS performed at MUSC, Charleston, SC
4/5/2018MRI BRAIN W/WO CONTRAST

Status post subtotal resection of left temporal mass with residual enhancing
tumor along the medial margins of the resection cavity measuring approximately
2.4 x 3.3 cm. Additional enhancing satellite nodule along the posterior
inferior aspect of the resection cavity compatible with residual tumor.

Similar mass effect and partial effacement of the left lateral ventricle with 5
mm rightward midline shift.
4/6/2018NEUROPATHOLOGY REPORT - DIAGNOSIS: GLIOBLASTOMA MULTIFORME WHO GRADE IV

(PARTIAL COMMENTS FROM REPORT DATED 4/6/2018)
Date Collected: 4/4/2018 15:05
Diagnosis
A. BRAIN, LABELED AS "TUMOR", RESECTION:
· GLIOBLASTOMA MULTIFORME, WHO GRADE IV
· IMMUNOHISTOCHEMICAL STAINS:
o IDH-1: NEGATIVE
o GFAP: POSITIVE
o SYNAPTOPHYSIN: NEGATIVE
o KI-67: PROLIFERATIVE INDEX OF 10 %

B. BRAIN, LABELED AS "TUMOR", RESECTION:
· GLIOBLASTOMA MULTIFORME, WHO GRADE IV
4/19/2018MRI FUNCTIONAL BRAIN
4/20/2018MRI BRAIN LAB WITH CONTRAST
4/20/2018Surgical Resection performed by Dr. Allan Friedman, Duke

Loss of right peripheral vision in both eyes post surgery
4/21/2018MRI BRAIN W/WO CONTRAST

FINDINGS: 
Postoperative changes of left temporal craniotomy with subjacent resection cavity within the left temporal lobe demonstrated. Surrounding increased signal on T2 weighted imaging is unchanged. There are blood products along the margins of the resection cavity. There are small areas of superimposed contrast enhancement along the posterior margin (series 12 image 90),medial margin (series 12 image 95), inferior margin (series 12 image 81), and superior margin (series 12 image 101). The areas of residual contrast enhancement are largely improved from intraoperative MRI. Trace extra-axial fluid and dural thickening at the craniotomy site. There are expected postoperative ischemic changes surrounding the margins of the resection cavity.

No hydrocephalus. The basal cisterns are maintained. Intracranial flow-voids appear normal. The orbits, mastoid sinuses, and visualized paranasal sinuses are unremarkable. 

IMPRESSION:
Status post left temporal mass resection with foci of contrast enhancing tumor along the margins of the resection cavity.
5/17/2018 Day 1 of 6 week  Radiation/ Temozolomide therapy (MUSC, Charleston, SC)
6/4/2018SEIZURE (occured 2 days after gradually stepping down Dexamethasone to 0mg/day)

 - MRI & CT scan performed

“Postsurgical changes of subtotal resection of left temporal mass with increased size of the resection cavity and likely increased local mass effect with entrapment of the temporal horn of the left lateral ventricle and slightly increased medialization of the left uncus. The component along the resection cavity demonstrating elevated CBV has decreased in size from prior studies.
Overall, these findings are suggestive of evolving post-treatment related changes with persistent residual tumor.Stable 5 mm rightward midline shift.”

- Increased dose of Keppra to 1g 2x day

 - Increased Dexamethasone to 6mg 2 x day (to gradually step back down)
6/8/2018MGMT GENE METHYLATION ASSAY - “GENE METHYLATION NOT DETECTED”
6/8/2018PATHOLOGY - GENERAL/OTHER - “ NEGATIVE FOR IDH1 R132H MUTATION”
6/27/2018Completed 6 weeks of Radiation/ Temozolomide treatment
7/11/2018SEIZURE (occured 2 days after gradually stepping off dexamethasone)

 - MRI & CT scan

“ADDENDUM: Similar appearance of a linear area of incomplete filling in the posterior superior sagittal sinus. This has been present on multiple prior studies, including the patient's original outpatient imaging and may reflect an underlying dural reflection or potentially chronic sequela of remote partial filling defect. No occlusion of the sinus flow is seen.
IMPRESSION: Posttreatment changes from subtotal resection of left temporal mass with persistent residual tumor and slightly decreased size of the resection cavity.Slightly increased vasogenic edema predominantly along the left insular region. Stable 5 mm rightward midline shift and early left uncal herniation.
No acute infarction.”

 - Increased Keppra to 1500mg 2 x day

 - Increased Dexamethasone back to 6mg 2 x day
7/13/2018FOOT DROP IN LEFT FOOT (possible stroke during seizure, MRI of spine schedules for end of month)
7/27/2018MRI BRAIN W/WO Contrast

“Extensive irregular enhancement of the resection cavity extending to the ependymal surface of the left lateral ventricle, appearing slightly increased in size. Significant increase in relative CBV within areas of enhancement and nonenhancing T2 hyperintensity. There has however been interval reduction of overall mass effect and rightward midline shift.”
8/1/2018DAY 1 METRONOMIC TEMOZOLOMIDE (100MG/DAY)

STARTED DISULFIRAM 250MG/DAY + COPPER 2MG/DAY

MEDICATIONS & SUPPLEMENTS:

NO Rxs:
- Keppra: 1500mg 2 x day (dose has increased 2 x after seizures)
- Dexamethasone: 6mg / day. (dose has varied due to seizures)
- Temozolomide: 100mg daily (metronomic schedule)

OFF LABEL RXs:
- Minocycline:  100mg 2 x day (May 17 - present)
- Metformin; 500mg 3x day (escalted to current dose starting May 17th)
- Chloroquine: 250 mg (May 17 - present)
- Disulfiram: 250mg / day (August 1 - present)

SUPPLEMENTS:
- Copper: 2mg (taken with Disulfiram)
- Milk thistle: 1000mg 2 x day
- Curcumin (Longvida): 1600mg / day
- Fish Oil: 1000mg / day
- Boswellia: 3g / day
- Turkey Tail (PSK): 3g/day
- Soy Isoflavones (Genistein, Daidzein, Glycitein) ?mg. 3 gelcaps/day
- Melatonin: 20mg at bedtime
- Vitamin D3: 10,000 IU/day
- Selenium: 200mcg / day
- Pterostilbene: 450mg / day
- Green Tea Extract: 750mg 3 x day
- CBD oil (Palmetto Harmony): 1ml 2 x day

QUESTIONS:

1.  MEDICATIONS AND SUPPLEMENTS: Are there any others medications or supplements I  should add  to his cocktail at this point (currently 
doing 100mg temozolomide, daily)
 - Celebrex?  I had this on my list, but I had trouble filling the Rx
 - THC ?  He is currently taking CBD oil, but wanted to refrain from the THC bc he is still an active Reservist in the US AF. 

2. Dexamethasone - We have tried taking him off steroids twice, both times resulting in seizure.  I have read that dexamethasone can inhibit the effectiveness of chemotherapy, but he obviously continues to struggle with swelling.  Any thoughts?  

3. UNDERSTANDING THE PATHOLOGY, BRAIN BIOMARKERS, ETC
    • MGMT GENE METHYLATION ASSAY - “Gene Methylation NOT detected” = UNMETHYLATED
    • NEUROPATHOLOGY REPORT:
    • Date Collected: 4/4/2018 15:05
      Diagnosis
      A. BRAIN, LABELED AS "TUMOR", RESECTION:
      · GLIOBLASTOMA MULTIFORME, WHO GRADE IV
      · IMMUNOHISTOCHEMICAL STAINS:
      o IDH-1: NEGATIVE
      o GFAP: POSITIVE
      o SYNAPTOPHYSIN: NEGATIVE
      o KI-67: PROLIFERATIVE INDEX OF 10 %

      MICROARRAY COMMENT:
      1p/19q co-deletion - Not detected
      +7/-10 - DETECTED
      CDKN2A/B homozygous deletion - DETECTED
      EGFR amplification - Not detected

  • BRAIN BIOMARKERS (IHC, FISH):
    • IDH1:  NEGATIVE, R132H IDH1 MUTATION WAS NOT DETECTED.
    • EGFR does not exhibit amplification.
    • EGFR RECEPTOR IHC ANALYSIS:Approximately 50% of the tumor cells exhibit 2+ staining of their cell membrane (score 2+), indicating that they DO express epidermal growth factor receptor.
    • EGFR VIII IHC Analysis:  none of the tumor cells exhibit staining for EGFR VIII (Score= 0)
    • IDH1 IHC Analysis:IDH1 mutations result in a histidine at codon 132.  An antibody specific for the IDH1-R132H mutation is NEGATIVE
    • Brain IHC Analysis:
D2C7 IMMUNOHISTOCHEMISTRY ANALYSIS:
Approximately 70% of the tumor cells exhibit D2C7 detectable EGFR staining of their cell membrane (score 2+), indicating that they DO express at least some portion of the epidermal growth factor receptor protein.

POLIOVIRUS RECEPTOR (PVR) IMMUNHISTOCHEMTRY:
Approximately 90% of the tumor cells exhibit 2+ staining of their cell membrane (score 2+). The endothelial cells stains positively (3+) and serves as a internal control.

    • TERT TARGETED MUTATION ANALYSIS: Positive.
TERT promoter mutation detected (C228T, c.-124C>T). 

CAN SOMEONE PLEASE HELP ME UNDERSTAND THESE FINDINGS?
I understand the implications of his tumor being UNMETHYLATED, but I am struggling to understand the rest of it.

Also, I am waiting on the results from Foundation One, and hope those results prove useful.

Monday, 20 August 2018

Yes or no on antidepressants?

Hi everyone,

I am finding some conflicting information on whether antidepressants with seratonin can contribute to progression. My husband is on a small dose of sertraline (Zoloft) every day. Is this something we should hold? I have for now as the dose is very small...

Any natural antidepressants that might be worth trying?

Thanks!
Abby


This just in... Looks promising !

https://corporate.dukehealth.org/news-listing/duke-team-finds-missing-immune-cells-could-fight-lethal-brain-tumors?h=nl

Sunday, 19 August 2018

New to the blog.  Many thanks to all who share their experiences with brain tumors.
I’m curious if anyone has information on BMQ-350.

Thursday, 16 August 2018

12 cycle vs 6 cycle adjuvant TMZ?

My husband is finishing up cycle 4, our medical provider (Kaiser) does six rounds, so I'm curious if there's any benefit to seeing if more is better.

I know this was discussed in 2017 - Stephen posted a link to an Indian study/review article that said 12 cycle had improved PFS/OS but with big caveats about how more studies were needed.  I've now seen a more recent study looking at the comparison between 6 and 12 Extended Dosing (12 Cycles) of Adjuvant Temozolomide in Adults with Newly Diagnosed High Grade Gliomas: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines seem to draw similar conclusions, though a couple of studies in Spain say that 12 cycles is a better choice for older patients or patients with AA (not GBM).

At the time Stephen's thoughts were to 1) go for 12 rounds (or possibly more if tolerated) if the tumor is methylated and if there weren't financial means to pursue immunotherapy, and 2) with an unmethylated tumor and financial resources, stop at six rather than continue to build toxicity to bone marrow and blood counts.  Since we fit in the latter category I'm thinking that the six is fine, but I wanted to see if anyone here had additional thoughts or concerns.  We have no additional tumor tissue (biopsy surgery only) and didn't have the right markers for the CAR-T treatment at City of Hope, so I'm not even sure if there are vaccine options to realistically pursue.

Thoughts?

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