Hey all, thanks for creating and maintaining this fantastic forum for patient-driven protocol development. I wish I'd found this a year ago when my partner was first diagnosed with GBM. I definitely would have pushed for adjuvant complementary therapies during the initial treatment phase (Stupp protocol plus Optune). My partner was first diagnosed in Jan 2017 and the first recurrence showed up last month. Two surgeries, two gross total resections. The recovery from the first was fairly smooth, but this one has been rough.
I'm getting some pushback from doctors about using botanical extracts, and I'd like to know how people here handle that sort of thing. The complaints are that these extracts are not standardized and poorly regulated, so varying dosages, contaminants, or even unknown active ingredients might cause side effects or unexpected interactions with other treatments. A vascular specialist said he’s seen a lot of weird things happen with supplements, and our hematologist agreed. My partner has a gnarly blood clot that requires intervention, which is why those doctors are involved. For what it’s worth, our oncologist didn’t raise any of those concerns.
At my insistence, we’re crafting a custom treatment protocol for the recurrence. Monotherapies and control arms make clinical trials less interesting to us. We started CCNU and pembrolizumab last week. Our oncologist is conservative with advice but is willing to let us try whatever is available. I’ve been looking to add other treatment modalities through OTC supplements. I got my partner on Vitamin D and calcium right away (not sure why every cancer patient isn’t put on these immediately), and I have melatonin and PSK ready to go. I’m also strongly considering curcumin, ECGC, boswellia, THC/CBD, and lipoic acid.
How do people here deal with the sorts of concerns raised by these doctors? Do you find that weird side effects and interactions are rare, or are they common but just worth the risk at this point? Does everyone end up just ignoring some doctors sometimes?
Thanks,
Brandon
How is your partner doing after Keytruda infusion? Mine has his first one today (also for GBM recurrence). I'm wondering what to expect. I've read that Celebrex can be helpful with Pembrolizumab: http://btcocktails.blogspot.com/2015/09/aspirin-or-celebrex-synergize-with-anti.html
ReplyDeletehttp://www.bioworld.com/content/nonsteroidal-anti-inflammatory-drugs-boost-antitumor-immune-response
http://astrocytomaoptions.com/immunotherapy/
We also wonder if we should stop other drugs he is taking like minocycline, metformin, vermox.
He was extremely tired afterward, sleeping most of the rest of the day and much of the next day. I'd say it took about 4 days overall for the fatigue to fully dissipate. It's hard to know if the pembro alone was responsible, since he took CCNU two days prior, but fatigue is a common side effect.
DeleteWe've been told from the beginning to steer clear of NSAIDS, so we haven't touched them. I'll have to look more closely at that research. Looks like it's about the anti-tumor effects, not side effects.
How did your partner do with the infusion today?
I would not continue minocycline in combination with Keytruda or other checkpoint inhibitors. There are clinical studies showing the importance of gut bacteria in response to checkpoint inhibitors, and an antibiotic such as minocycline could interfere with this by killing off beneficial gut bacteria.
Deletehttps://www.sciencedaily.com/releases/2018/03/180303090356.htm
DeleteAntibiotics may impact cancer treatment efficacy
"It is clear in animal models that if you wipe out the intestinal microbiota, like you do with antibiotics, it will attenuate the chemotherapy efficacy," says Zhou.
Ofcourse, it may not translate to humans...but something to keep in mind anyway
Dear Justyna,
DeleteCould you please send me, if possible, your e-mail address (st.sobieski@gmail.com), I would like to ask you regarding the treatment.
Many thanks,
Has there been any molecular testing done on the tumor? IDH1 mutation? MGMT status? EGFR status?
ReplyDeleteWas there any IHC (immunohistochemistry) testing for PD-L1 expression in the tumor sample, prior to getting a prescription for pembrolizumab? [this isn't routine testing though]
CCNU and pembrolizumab aren't necessarily great together, as the CCNU could compromise lymphocyte counts. However if MGMT status is methylated, I would keep the CCNU, unless there has been testing that predicts response to pembrolizumab (PD-L1 expression, hypermutation, signs of T-cell infiltration into the tumor).
My attitude towards doctors is that they know what they know, but there is a lot that they don't know. Allow them to contribute what they know, but do your own research and make your own decisions (to the extent possible). Oncologists on the whole (there are exceptions) are ultra-conservative, which is why this blog even exists. Sometimes it's appropriate to not listen to one's doctor.
If you haven't already, check out Ben Williams book "Surviving Terminal Cancer" and Dominic Hill's documentary film of the same name.
https://www.survivingterminalcancer.com/
MGMT unmethylated, IDH1 wildtype, no mutations or copy number alterations in EGFR. I haven't seen the GlioSeq on the new sample yet, but the onco nurse reported these: TERT mutation, NF1 mutation, PTEN deletion, RB1 deletion, and CDKN2A deletion. We're waiting for more extensive genetic analysis from Tempus. Should be any day now. PD-L1 testing is being done with it. I'll get the GlioSeq on Friday.
DeleteHe tended toward lymphopenia on temozolomide, so low T counts are a concern, which is why I've been looking to complementary therapies for immune boosters (in addition to Neulasta). I suppose we could have waited for a diagnostic to indicate pembro, but it was something we could get, has a relatively low side effect profile, and seemed worth a try.
I'll have a look at the Williams book and Hill's documentary. Thanks.
For what it's worth NF1 mutation in GBM is most frequently associated with the mesenchymal subgroup (as opposed to classical and proneural groups).
DeleteI watched the documentary and found it extraordinary. It’s exactly what we needed at this moment, encouragement to continue confidently in the direction of greater self-directed intervention plus some hope that doing so might actually help. It’ll be interesting to see how our oncologist responds when I start asking for off-label prescription meds, which I will certainly do now.
DeleteThe discussion of ACT UP was especially interesting. They actually changed the way medical research was being done by refusing to participate in clinical trials. Hard to see the glioma community doing the same thing, without an existing civil rights movement to utilize, but it’s a fascinating idea. In any case, it’s very clear that patient welfare isn’t the top priority for the oncology establishment at present.
As it turns out, I had already seen Ben Williams’s work and didn’t realize it. Someone at the Brain Tumor Network forwarded me the Treatment Options document a couple of weeks ago, and I quickly found it invaluable. I only wish I had seen it (and this forum) a year ago. And now I realize that you (Stephen) are the one maintaining that document. I can’t thank you enough for the work you’ve done and continue to do. AstrocytomaOptions.com is impressive and helpful as well. That you’ve done this without any formal scientific training is all the more impressive. I have a doctorate in the philosophy of physics and I still feel overwhelmed.
The Tempus results came back and they’re interesting. I’ll post a new topic to get feedback.
Why were you told to steer clear of NSAIDs? Was there any reason given?
ReplyDeleteTo prevent GI problems, I believe. I think the heavily advised against it while he was on dexamethasone, and maybe that proscription just stuck with us. I'll have to ask the onco nurse about it.
DeleteThe GI issues are more of a concern with non-specific NSAIDS, such as aspirin, ibuprofen, naproxen. This is due to their inhibition of COX-1. Selective COX-2 inhibitors should be much less problematic in terms of GI problems.
DeleteI wrote the following for the CUSPND entry on celecoxib:
"In this last study, considering all patients not taking aspirin, patients taking celecoxib actually had a lower rate of gastrointestinal ulceration and hemorrhage than the placebo group, with a risk ratio of 0.9 in the 200 mg celecoxib twice daily group, and a risk ratio of 0.8 in the 400 mg twice daily group. There were over 450 patients in each of these groups (Bertagnolli 2006)."
The literature references warning against NSAIDS + dexamethasone mostly date from the 1990s and earlier, before selective COX-2 inhibitors were even approved.