A friend (48 yr old male, full resection 2 mos ago) has recently completed 6 weeks of RT and TMZ. He has discussed the possibility of metronomic vs. 5-day dose-intense schedule due to unmethylated MGMT status and EGFR overexpression mutation. He has a medical oncologist and a neuro oncologist. The medical oncologist didn't see one way or another would be preferable. The NO is still considering. Per Ben Williams, we know it is "worthy of consideration" to try the medium-dose metronomic schedule for unmethylated, amplified EGFR. I have read the study that seems compelling, but it is not conclusive based on being retrospective and having potential selection bias. Is there any other data or personal experiences on whether if given the choice, one would choose a metronomic schedule early on instead of doing this only at a recurrence for unmethylated EGFR amplied patient?
Thank you for this great resource. I will include his cocktail in case you have other recommendations or questions.
Keppra 500/2X
Pepcid 20 mg/2X
Celebrex 200 mg/2X
Atorvastatin 40 mg/2X (will increase to 80)
Mebendazone 100 mg
Valcyte 900 mg/2X
Bosweillic acid 3,000 mg
SBI protect (for GI protection)
Omega fish oil 1250 mg/2X
Coriolis/PSK 4.4 mg
Vit D 5,000 IU
Curcumin 1,000 mg (Seems to cause diarrhea, trying to increase)
Probiotic
Selenium 200 mcg
Magnesium 120 mg
Green tea extract 1,000 mg/2X
Melatonin 20 mg
Ginseng 500 mg
Astragalus 1,500/2X
Milk thistle
Strict Ketogenic diet
Doctor advised against DCA (says not enough data to support), chloroquine (risk of retinopathy) or CBD oil (short-term memory problems), LDN (doesn't think it is effective)--if anyone wants to comment on these.b
Finally, he is on the fence about Optune if you have any experience with the lifestyle aspect of using it. Our gratitude and best wishes to all of you.
I have to take credit for authorship of that section of the Treatment Options update (I've taken over the updates from Ben since 2015). I do believe there may have been selection bias in that retrospective study on metronomic TMZ (Cominelli et al 2015).
ReplyDeleteHowever, figure 5 of that study and the last section of the text before the Discussion also showed the metronomic schedule led to a significantly decreased percentage of EGFR amplified cells versus the standard schedule, an observation less susceptible to selection bias.
So my opinion that it is worthy of consideration still stands.
The risk of retinopathy with 250 mg chloroquine phosphate daily for several months is low.
See the chloroquine section here:
http://btcocktails.blogspot.com/p/toxicities.html
Thank you so much for responding. You are an invaluable resource. So what would you do regarding the choice of a metronomic schedule or standard 5/28 schedule, if it was your loved one with these characteristics? My friend’s oncologist seems open to trying something different, but actually recommended the “dose dense” schedule of 3 weeks on, one week off, rather than the metronomic. I am guessing that is because my friend is young and otherwise healthy, so probably presumed to be able to tolerate a higher dose. However, my understanding from Williams (maybe you?) is that metronomic is likely preferable to dose-dense. Would you choose the metronomic? It’s so difficult when the “experts” leave it up to us lay people.
ReplyDeleteThe metronomic schedule used in the Cominelli study was a high dose metronomic schedule, 75 mg/m2, as opposed to the standard dose metronomic 50 mg/m2. The "dose dense" schedule uses 75 to 100 mg/m2 three weeks on, one week off. This means that the high dose metronomic schedule (75 mg/m2 every day) is actually a higher cumulative dose than the 75 mg/m2 three week schedule.
ReplyDeleteThere was a clinical trial published in 2013 showing that the dose dense schedule isn't superior to standard schedule in the general GBM population. (Dose-Dense Temozolomide for Newly Diagnosed Glioblastoma: A Randomized Phase III Clinical Trial, https://www.ncbi.nlm.nih.gov/pubmed/24101040 ). However trials haven't looked at the effect of different TMZ schedules according to the EGFR status of the tumor.
You could try the 75 mg/m2 for three weeks schedule and if he tolerates that well you could consider 75 mg/m2 every day as they used in the Cominelli study, and that could be reduced to 50 mg/m2 or 40 mg/m2 daily as your friend runs into problems with low blood counts. It's difficult to predict beforehand what will work and how much he'll be able to tolerate. I think it's important to try various things and make adjustments as you go.
75 mg/m2 daily TMZ is the same schedule that's used during radiation, so his blood counts at the end of radiation will give some indication of how well he'll tolerate the higher dose metronomic schedule.
DeleteThank you so much for your thoughtful replies. The dosing information is very helpful, and I'm sure he will discuss it with his oncologist.
DeleteMy husband's tumor is unmethylated with wild type IDH. He was not prescribed TMZ when he was diagnosed with GBM in 2/16 because the NO thought it would be ineffective, but has been taking it daily since 1/18 after his tumor spread to a new area. His dosage is 50 mg/m2. He also takes Celebrex and Prozac to potentiate the TMZ, as supported by research on this site, and uses Optune.
ReplyDeleteEvery MRI since January has shown that the tumor was stable or shrinking. My husband bikes, hikes, lifts weights and works part-time and looks terrific. The low-dose TMZ is very tolerable. He has no nausea or abdominal problems and has been able to maintain his weight.
I don't think he would have survived nearly three years with unmethylated GBM without low-dose TMZ and Optune.
Good luck,
Margaret
That's fantastic, Margaret!! Thank you so much for sharing his experience. It is really helpful to hear about people who are doing better than expected. Best wishes for his continued good results.
DeleteHow does he feel about Optune? Does it interfere much with his quality of life?
Dear ResearchFriend -
DeleteI wish I could tell you otherwise, but my husband hates Optune. He is an active persona and an avid biker and feels encumbered. He also chafes at having to worry about weather (too hot? too wet?) and battery power. He is measurably happier when his scalp is resting between array changes. He keeps hoping (in vain, I expect) for our doctor to okay giving it up.
I think he also feels guilty at the time I spend on array changes.
M
TYpo - active person, not persona.
DeleteThank you, Margaret. Appreciate your candor.
DeleteHaving said all that, he would never quit unless he had years of clear scans!
DeleteThere is also an expanded access trial for ABT-414 targeting the EGFR-amp https://clinicaltrials.gov/ct2/show/NCT03123952
ReplyDeleteThank you, David. We will look into this. :)
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