Dear Stephen, Dear All,
I’m so sad that so many of us are finding ourselves here. You have my immense gratitude, Stephen, for the invaluable knowledge that you share with us all and for this incredible website.
I was diagnosed with GBM in July 1018. I’m a single parent of a young child. This nightmare has been devastating.
My tumor was very large, in my right parietal cortex, 100% resected. It was 94% MGMT methylated. It had TP53 mutations in three variants, no IDH1 mutation, CBL mutations in two variants, CDKN2A/CDKN2B homozygous deletions, Stag2 mutation, PDGFRA mutations in two variants (one with 85% frequency), and very high amplification of PDGFRA (~25,000 reads (>50x)) .
I’m now completing my 12th TMZ maintenance cycle. I have not yet had a recurrence and know it’s a race against the clock. The tumor sample was unfortunately set in paraffin, so I’m not a candidate for DCVax-L. I’ve been trying to raise funds for the CeGaT peptide, but coming up with all that money is a longshot for me.
1] Does anyone know if there are any other vaccines/immunotherapies for which I might qualify?
2] I’m wondering if anyone could provide a recommendation of what treatment to pursue after a year of TMZ. I battled with my neuro-onc to use CCNU on day 1 of my TMZ maintenance cycles, but she would not relent. In fact, she has refused every request I’ve made of adding agents in addition to TMZ, such as Keytruda, to prolong my survival. Is my only option at this point in terms of ‘standard of care’ metronomic low-dose TMZ?
3] Is there such a treatment as metronomic low-dose CCNU? If not, might I push to now receive CCNU in a conventional manner, assuming my blood counts are okay?
4] If I proceed with metronomic low-dose TMZ, should I avoid low-dose metronomic Accutane?
5] I had to stop high-dose Tamoxifen owing to concerning side effects. Would it have any value (such as for protein kinase inhibition) at a much lower dosage? Is there another effective anti-angiogenesis medication to use instead?
Following is my current daily combination of off-label medications. I would so greatly appreciate any feedback on the dosages (are my current ones at therapeutic levels?) and what agents I might consider adding. Thank you so very much!
Celebrex 400 mg
Metformin 1500 mg
DCA 1000 mg (on/off owing to significant neuropathy)
Lansoprazole 30 mg (120 mg 3 days before TMZ, during, 2 days after)
Chloroquine 250 mg
Naltrexone 4.5 mg
Minocycline 200 mg
Melatonin 20 mg
With gratitude and praying for us all!
~Joule
Dear Joule,
ReplyDeleteWould the Optune device be something you might consider?
Sending Love, healing and strength to You.
Kelly
Dear Joule,
ReplyDeleteI can only imagine how difficult his has all been for you.
What geographic area are you in (what state or city are you close to)? It could pay to start looking at clinical trial options for recurrent GBM. I could make some suggestions, but geography is usually a big factor in which trials somebody is most likely to pursue.
With TP53 mutations and CDKN2A/B deletion, a drug like abemaciclib would be worth looking into or asking about. This is a breast cancer drug that received FDA approval in 2017. It's not approved for brain tumors though it is in clinical trial for recurrent GBM.
A drug such as imatinib (Gleevec), approved in 2001 for certain leukemias, could have some anti-PDGFRA activity, though again, not approved for brain tumors.
I'm not sure if you've contacted CeGaT already, but what I understand is that first they would have to sequence the DNA of the tumor tissue, which costs around 5000 Euros (give or take), and only after sequencing would they be able to determine suitability for a multi-targeted peptide vaccine.
After completing monthly TMZ cycles, I do believe Accutane makes sense as a maintenance therapy. Based on studies such as this:
http://sci-hub.tw/https://journals.sagepub.com/doi/abs/10.1177/1078155213483348
"Isotretinoin maintenance therapy for glioblastoma: A retrospective review*"
The dose used in the above study was 100 mg/m2/day on days 1-21, which is actually high dose. 100 mg/m2 for an adult with body surface are of 1.7 to 2 square meters would be 170 - 200 mg per day (divided into two daily doses). The maximum recommended dose for adult acne patients is 2 mg/kg/day or 120 mg per day for a 60 kg adult. So the daily doses used in glioblastoma trials have been quite high dose, and do come with some expected side effects (see table 3 in the study referenced above).
I've never heard of low dose metronomic lomustine (this doesn't mean it couldn't be done). But intensive chemo does take a toll on immune cell counts such as T-cells, and if you are seriously considering immune therapies, you might want to preserve your healthy blood counts for future treatments. On the other hand doing a single round of lomustine could knock back any small subpopulations in the tumor that had developed a TMZ resistance (for example cells that have mismatch repair defects making them immune to TMZ treatment but more sensitive to lomustine).
I will have to continue this comment at a later time in the next few days.
S.
Tmz mainly alkylates single strand locations on dna and so while it is fairly easily repaired it attaches at enough locations that hopefully all of it doesn't get removed by repair mechanisms. Daily tmz basically is an attempt to keep the repair machinery too busy to keep up.
ReplyDeleteCCNU will make some cross linked lesions (from one strand to the other) which are much harder to repair and a different mechanism than TMZ single strand lesions. It is also a lot more toxic to normal cells and unlike tmz it kills blood stem cells causing a permanent decline in blood counts. So doing it daily would be very questionable.
But it sounds like you were pushing your NO to do TMZ AND CCNU at the same time and they refused. So as you noted asking them to just do CCNU alone is a lot more reasonable, though typically it would be given at recurrence. But if your MRI is clear and you've done 12 rounds of tmz then continuing more chemo at all may be overtreating and simply building resistance as well as weakening your immune system. Hard to say though.
In general it seems like you would be classified as stable at this point and so that cuts out a large # of trials. But NO's are often willing to fudge the MRI measurements if there is a little bit of flair change to go on. So you might still be able to get in a trial. Be aware that it can take many months to get into a trial and so investigating options now and proceeding as if you were recurrent would give you the edge to act fast if the time came.
Dear Stephen, dear bs1966,
ReplyDeleteThank you both so very much for your kind and very helpful responses!
I'm on the West Coast of the States. UCSF and UCLA would be good options for me for trials. I had traveled to UCLA for a consultation and, if I have recurrence, hope to get into its DCVax-L trial if it's still open (after surgery and getting the sample flash-frozen). I would definitely like to learn of any other local trials that don't require recurrence, if you come across any :) I'm of course looking now too. The idea to fudge my mri (there's definitely enough flair) to be accepted to a recurrence-only trial is certainly something I'd consider.
I've been communicating with CeGaT, but it's so costly and I'm still trying to raise the funds, even just for the sequencing. It seems to be my only vaccine option at this point (?).
I like the approach, in follow-up to my 12th TMZ cycle, to do one round of CCNU when my counts replenish, followed by maintenance Accutane.
But if I undertake metronomic TMZ, would even low-dose daily Accutane be contraindicated with it?
It's a good point to consider that continuing any more chemo after 12 cycles may be overtreating and building resistance while weakening my immune system. My counts have categorically been low; I'm just scared to not do anything.
As a subsitute for Tamoxifen for anti-angiogenesis, my regular doctor suggested I try the copper-depleting medication Tetrathiomolybdate. Is anyone familiar with that? It seems beneficial in other hard-to-treat cancers, but I couldn't find any information on its use with GBM.
Thank you both again so much!