Hi all,
My husband is being treated for his second GBM
relapse. He's receiving irinotecan and Avastin at the moment and his
last two MRIs have been stable, interpreted as radiation necrosis. The
tumor size hasn't changed at all (close to 4cm in diameter) and he's
experiencing neuropathy on his right side, speech difficulties and major
brain fog on some days, but overall doing okay. In fact, he has
improved significantly since July, when he could barely form sentences,
was losing function of his right side and was very sensitive to noise
and light. Now he's going on daily walks, can spend time around our
rambunctious kids, and his speech is much better-- we are feeling very
grateful.
I'm considering adding to his
cocktail but I'm not sure what to add and what we should prioritize when
talking to his doctor. Here's what I'm considering, I'd be open to any
suggestions beyond this as well. His tumor is MGMT-methylated and
IDH1-mutant.
-Chloroquine-- Is this
something we would have to source on our own? And if so, is it still not
available in the U.S.? Has anyone purchased from the vendor in Canada?
-Mebendazole-- What is the recommended dosage for this? Is it potentially more effective than chloroquine?
-PARP inhibitor-- Is there off-label use approved with olaparib in the U.S.? And can this be used with his current treatment?
-Disulfiram- Is this potentially a bad idea if he's already experiencing neuropathy?
-Sodium
phenylbutrate-- I haven't read too much about this one other than a
couple of successful case reports. I'm assuming this is something we'd
have to get his doctor to prescribe but I'm not sure if it's worth
pursuing.
-Sativex (or similar)- Where is this available? And what is the recommended dosage?
I think I'm most interested in introducing mebendazole, disulfiram, Sativex and a PARP inhibitor, if possible. Interested to hear others' experiences with any of these.This blog/community is an excellent resource-- thank you in advance!
You didn't mention it, but is he using Optune? My husband (unmethylated, IDH negeative) has been doing well in the the year since diagnosis of his second recurrence with Optune, daily Temodar, Prozac, Celebrex and Keppra. We were unable to obtain Mebendazole and Metformin caused serious weight loss.
ReplyDeleteAlso, I strongly recommend alpha lipoic acid for the neuropathy. After my husband used it, he never experienced another episode of neuropathy and it has no discernible side effects. I think we bought it from Amazon.
Good luck!!
How much Alpha Lipoic Acid does your husband take?
DeleteThank you!
Candy
That’s interesting, he was taking ALA before this recurrence and I just sort of halted it. I wasn’t sure if it was helping at all. But I didn’t think of it for neuropathy, thank you!
ReplyDeleteHe tried Optune briefly last year and it caused some side effects (increased blood pressure, nausea). So we haven’t revisited Optune yet. May I ask why you couldn’t get mebendazole? And has he been on daily Temodar the past year?
So glad to hear your husband is doing well.
Dear Abby -
ReplyDeleteAre you really sure that the nausea and high blood pressure were caused by Optune? The only side effect I have heard of is scalp irritation, which has been somewhat of a a problem.
I can't remember the problem with Mebendazole. My doctor has been so great about every crazy thing we have tried that I didn't push it when he demurred.
My husband has been daily TMZ since January, so it is not quite a year. He has tolerated it really well. He was advised against the SOC when he was diagnosed in 2016, so the fact that it is working is a welcome surprise.
Interesting. What is the daily dosage? Is this his second go with tmz?
DeleteThe side effects my husband had during Optune treatment went away after he discoutinued so we’re pretty sure it was from Optune.
DeleteAn old generic drug like mebendazole should be dirt cheap (and still is in some countries).
ReplyDelete" Mebendazole, meanwhile, was an inexpensive generic drug for decades, then went off the market in 2011. Amedra also purchased the rights to that drug, so it owned the only two prescription pinworm treatments available. The company was acquired by Impax Laboratories in 2015, and by January 2016 it launched a chewable version called Emverm, pricing it around $400 per pill. The inexpensive version of mebendazole is no longer available."
https://www.consumerreports.org/drugs/pinworm-treatments-expensive-drug-mistake-you-dont-need-to-make/
So the main problem with mebendazole is availability and especially pricing (exorbitant prices for what should be a very cheap drug)
Olaparib is an FDA-approved drug for certain types of ovarian and breast cancer. It could be legally prescribed for brain tumors, but again the limiting factor is going to be the cost, because it isn't approved for brain tumors so insurance isn't likely to pay. The monthly cost for olaparib in 2014 was about $12,000 USD.
ReplyDeleteSodium phenylbutyrate does seem to have activity for at least some brain tumor patients, but we have no biomarkers to predict who will respond. Meanwhile, at a dose of 9 grams per day, the monthly cost would be about $3300, even for the generic version (as of 2016), if you could even find a source for it.
ReplyDeleteSativex is approved in Canada and some European countries, but not in the USA. But as cannabis has been legalized in some states, and will be legal across Canada in two days time (Oct 17), finding another high quality cannabis product shouldn't be too much of a problem. Sativex is simply a 1:1 THC:CBD spray.
ReplyDeleteIt might be worthwhile to review Ben Williams 1995-1996 cocktail, which I've summarized near the end of this article:
ReplyDeletehttp://astrocytomaoptions.com/exploring-strategies-for-idh1-mutated-gliomas/
Particularly Accutane and high-dose tamoxifen could be interesting, though these are not without potential side effects.
Thanks Stephen. I'm not sure tamoxifen is okay to use with Avastin but will ask his doctor. Reading the section on Accutane on your site, you note that one study found it might be antagonistic with temozolomide. Do you happen to know if that may also be the case with other chemotherapies? Is Accutane primarily a maintenance drug or could he use it in between his chemo cycles?
DeleteChemotherapies like TMZ and lomustine are only effective on dividing cells. One theory is that Accutane leads to fewer cancer cells dividing at the time chemotherapy is applied, thus making chemotherapy less effective.
DeleteI think of Accutane as being a maintenance drug not to be taken with chemotherapy. It might be safe to take Accutane for a couple weeks in between monthly chemo cycles (Ben Williams did this for example), but I can't guarantee that.
Hi Abby, you were asking also about Sativex:
ReplyDelete"Sativex (or similar)- Where is this available? And what is the recommended dosage?"
This is available in Canada and some European countries.
The maximum dose used in the Sativex + TMZ trial for recurrent GBM was 12 sprays per day, which amounts to approximately 30 mg each of CBD and THC per day.
I'm not sure this 1:1 ratio is optimal though. Most people are limited by the amount of THC they can tolerate (this will increase over time), but CBD is tolerable in much higher doses. There is some mouse evidence that ratios of THC:CBD up to 1:4 or 1:5 are more effective than 1:1, even when the THC dose is held constant.
See figure 4 of this study:
http://sci-hub.tw/10.1016/j.bcp.2018.09.007
My general recommendation would be to find the maximum amount of THC tolerable, and then boost the CBD dose several times higher than that. One example would be 30 mg THC per day and 150 mg or more of CBD. CBD doses even much higher than that are tolerable.
However, there's not much solid clinical data to base these decisions on, and even less clinical trial data.