Hi folks/Stephen,
We had my mom's MRI about a month back, and her last MRI showed no growth of the disease, had no choline elevation(in the spectroscopy report) and didn't show perfusion either. She had a gross total resection and was diagnosed in Sep 2017.
She has completed her radiotherapy, 3 cycles of temozolomide and 6 cycles of lomustine+temozolomide. We moved to the Lomustine + Temozolomide protocol because her disease was methylated.
I'd like to get my cocktail reviewed from all of you, and want to know what are the next things that I should consider adding/updating on my cocktail so that things stable. I'd like to be prepared on what I should do next, and be prepared for a recurrence:
Following is my mom's current cocktail:
Diet: Low Carb High Fat/Ketogenic Diet
Supplements:
Following are the details from her biopsy
IDH1 and IDH2: Not detected
CHR 1p and CHR 19q: Negative for CHR 1p and CHR 19q codeletion
Methylation: Detected
Ki67 labelling index is 15-20%
Following is her FoundationOne report:
Genomic Alterations Identified
EGFR A289V – subclonal, amplification, EGFRvIII
PTEN I67T
CDKN2A/B loss
TERT promoter -124C>T
Additional Findings
Microsatellite status MS-Stable
Tumor Mutational Burden TMB-Low; 3 Muts/Mb
Additional Disease-relevant Genes with No Reportable Alterations Identified†
IDH1
PDGFRA
MY QUESTIONS
1. Has any one of you gone beyond 6 cycles of lomustine+temozolomide? How was your experience like, if you did? Because my mom's scans have been stable - the chemotherapy along with the supplements have definitely been working.
But because my mom's WBC counts have constantly been low(between 2-3k), and she gets affected by even the slightest of the infections - I'm not sure if I should go beyond the 6 cycle mark.
2. Should I consider adding anything, or updating anything in the current cocktail?
I have the following supplements that I plan to add:
- Low dose Naltrexone
- Valcyte(She was positive was CMV in her blood a a year back)
- Ruta 6 and Calceria Phos
Any other supplements that you would consider adding, which you think are high priority ones and that I've missed out on?
3. Are there any clinical trials/additional treatments that you would suggest doing beyond the current line of treatment that we currently are on?
4. The next important step that we want to consider is immunotherapy/dendritic cell therapy. Which places in your opinion are the best places that we should consider for immunotherapy? My mom's tumor is stored in formalin/paraffin, sadly.
5. Which are the doctors that we should consider speaking to next for an integrative approach to the disease? We are already in touch with Patrice Surley for naturopathic supplements. Would love to know about more doctors who you've had good experience speaking to, and how they can help.
I look forward to hear from you all!
We had my mom's MRI about a month back, and her last MRI showed no growth of the disease, had no choline elevation(in the spectroscopy report) and didn't show perfusion either. She had a gross total resection and was diagnosed in Sep 2017.
She has completed her radiotherapy, 3 cycles of temozolomide and 6 cycles of lomustine+temozolomide. We moved to the Lomustine + Temozolomide protocol because her disease was methylated.
I'd like to get my cocktail reviewed from all of you, and want to know what are the next things that I should consider adding/updating on my cocktail so that things stable. I'd like to be prepared on what I should do next, and be prepared for a recurrence:
Following is my mom's current cocktail:
Diet: Low Carb High Fat/Ketogenic Diet
Supplements:
Following are the details from her biopsy
IDH1 and IDH2: Not detected
CHR 1p and CHR 19q: Negative for CHR 1p and CHR 19q codeletion
Methylation: Detected
Ki67 labelling index is 15-20%
Following is her FoundationOne report:
Genomic Alterations Identified
EGFR A289V – subclonal, amplification, EGFRvIII
PTEN I67T
CDKN2A/B loss
TERT promoter -124C>T
Additional Findings
Microsatellite status MS-Stable
Tumor Mutational Burden TMB-Low; 3 Muts/Mb
Additional Disease-relevant Genes with No Reportable Alterations Identified†
IDH1
PDGFRA
MY QUESTIONS
1. Has any one of you gone beyond 6 cycles of lomustine+temozolomide? How was your experience like, if you did? Because my mom's scans have been stable - the chemotherapy along with the supplements have definitely been working.
But because my mom's WBC counts have constantly been low(between 2-3k), and she gets affected by even the slightest of the infections - I'm not sure if I should go beyond the 6 cycle mark.
2. Should I consider adding anything, or updating anything in the current cocktail?
I have the following supplements that I plan to add:
- Low dose Naltrexone
- Valcyte(She was positive was CMV in her blood a a year back)
- Ruta 6 and Calceria Phos
Any other supplements that you would consider adding, which you think are high priority ones and that I've missed out on?
3. Are there any clinical trials/additional treatments that you would suggest doing beyond the current line of treatment that we currently are on?
4. The next important step that we want to consider is immunotherapy/dendritic cell therapy. Which places in your opinion are the best places that we should consider for immunotherapy? My mom's tumor is stored in formalin/paraffin, sadly.
5. Which are the doctors that we should consider speaking to next for an integrative approach to the disease? We are already in touch with Patrice Surley for naturopathic supplements. Would love to know about more doctors who you've had good experience speaking to, and how they can help.
I look forward to hear from you all!
Sahil Hi!
ReplyDeleteFirst of all you are doing really good job regarding you Mom treatment. I wish you all the possible luck in the world to continue this battale as long as it is possible.
Now regarding your question, I could add smth about EGFRvIII, my Dad was diagnosed with GBM and was EGFRvIII positive, so in Israel we found treatment with rindopepimut which gave him 6-8 month after frist recurrence after Temodal course. All the possible trial is better check at https://clinicaltrials.gov/
As for doctors I could strongly recommend Duke Medical Center and Henry Friedman, M.D. - they have got some good trials with polio virus, but karnofsky performance score should be very high.
hope this helps, wish you all the best!
Thanks for posting all the additional info and Foundation results.
ReplyDeleteGiven the EGFR amplification, positivity for EGFRvIII and CDKN2A/B deletion, her tumor very likely belongs to the "classical" subtype of GBM.
The off-label/cocktail ingredient with the best clinical support for this type of tumor is probably chloroquine, so if she is tolerating that well I would try to keep that in her cocktail.
https://www.ncbi.nlm.nih.gov/pubmed/29377763
What doses of TMZ and CCNU is she at now? If blood counts drop too low you could consider reducing the dose of chemo. Or you consider lengthening the cycles from 6 weeks to a longer period.
If she is stable now she will be ineligible for most trials unless her tumor progresses. Most trials are either for newly diagnosed where the experimental treatment starts before or concurrently with standard treatments, or for recurrent cases with active tumor progression.
One thing to consider is that her type of tumor may be less responsive to BEV (Avastin), which is one of the standard options for recurrent GBM.
https://www.ncbi.nlm.nih.gov/pubmed/30680510
"EGFR amplification and classical subtype are associated with a poor response to bevacizumab in recurrent glioblastoma."
IOZK in Cologne Germany has developed a technique of applying hyperthermia and Newcastle Disease virus, after which they can extract tumor antigens from the blood to create a personalized vaccine in cases where there is no appropriate tumor tissue. Another option would be creating a peptide vaccine based on tumour antigens found in the FFPE tissue. There has been quite a bit of discussion of IOZK clinic here on the blog (click on the "IOZK_clinic" label from the menu on the right).
Any high quality cancer vaccine is going to be very expensive outside of a clinical trial though.
The chemo may have really knocked down her CD8 T-cell counts which could limit the efficacy of a vaccine. We still have lots to learn about how best to combine immunotherapy with chemotherapy.
Her long progression-free survival is encouraging, and something is clearly working. Are you able to travel for clinical trials if her tumor recurs?
Thanks so much for your response, Stephen. My answers and follow up queries here, would be great if you could answer:
ReplyDeleteStephen: What doses of TMZ and CCNU is she at now? If blood counts drop too low you could consider reducing the dose of chemo. Or you consider lengthening the cycles from 6 weeks to a longer period.
1. My mom was at 100 mg/m2 of Temozolomide and 110 mg/m2 of Lomustine. Since she had completed 6 cycles of this combination, and we switched to this protocol after 3 cycles of temozolomide, I'm not sure if I should go beyond this and have hence stopped further chemo, which is the major reason why I'd like to be more prepared for times to come.
Though I understand that the choice of 6 cycles chosen at the University of Bonn was rather arbitrary, I'm not confident of going beyond having done a total of 9 cycles already.(3 of TMZ, 6 of TMZ+Lomustine) Have you stumbled upon any patients who have gone beyond the 6 cycle mark of lomustine + TMZ, Stephen? Would love to know your experience, learnings and your suggestions on what to do next.
What I'm also concerned is on the decrease of the quality of her blood counts. Though they may recover completely, I'm not sure how good the quality of the blood counts shall be. I'm quite afraid if doing more chemo would do more harm than good. Would love your inputs here!
2. What would be the vaccine that you would suggest for an EGFRViii amplified, if not avastin? I'd love to me more prepared just in case a recurrence happens with using the right drug.
Would you suggest doing more TMZ and/or lomustine do avoid a recurrence completely in the first place?(Something which I know is statistically very unlikely)
3. I love the IOZK protocol, and think highly of it. But the number of times that they would suggest coming to Cologne might be indefinite, which seems really unfeasible for a GBM patient, since there is a lot of variance in her health everyday.
Would you suggest some other immunotherapy protocol for my mom? Any other clinics that you think highly of, given the fact her chemo is over and her tumor is stored in formalin/paraffin?
Stephen: Her long progression-free survival is encouraging, and something is clearly working. Are you able to travel for clinical trials if her tumor recurs?
4. Yes, we are open to travelling if there is a recurrence. Any specific trials that we should keep in mind for her?
Thanks so much for all your help again, Stephen! Looking forward to your help here :)