I am about to start radiation and temozolomide for the next 6 weeks and I'm not sure which specific drugs can be combined with TMZ during this stage. Can someone point me to a reference or if you have the knowledge on hand? I couldn't immediately find such a reference specifically for the radiation phase.
My neurooncologist told me that I should be very careful about taking additional drugs during this radiation as different combinations don't have proven efficacy (TMZ may decrease in efficacy) and the toxicity of combinations can also be unknown. So I've looked into this, but I would appreciate any feedback.
I understand that a different blog post (Rich cocktail), which might be a bit dated (3 years ago), is focused on treatment in general and not specifically for the phase of during radiation.
Here is the list that I would like to try out during radiation. Is there anything you would add/modify?
- Valproic acid (because I'm currently on Keppra, I may have to switch off of Keppra to take Valproic acid since I may not need multiple anti-seizure medications?)
- Metformin
- CBD Oil
- Iron supplement
- PSK
- Alkylglycerols (possible liver side effects)
- Green tea
- selenium
- magnesium
- Boswellia serrata
- Chloroquine phosphate
I'm MGMT unmethylated so I believe the TMZ efficacy doesn't seem as concerning.
Depakote (valproic acid/valproate) at a dose of 25 mg per kilogram body weight per day, divided into 2 daily doses was tested in a phase 2 trial for GBM with surprisingly good survival outcomes. The Depakote was started one week prior to radiation at a lower dose, and escalated up to the full dose by the first day of radiation. I believe the higher than usual dosage of Depakote was important, as typical anti-seizure doses might not be high enough for consistent HDAC inhibition.
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pubmed/26194676
Also tested in clinical trials along with radiation and chemotherapy (BCNU) was chloroquine phosphate (several small trials in Mexico). Positive outcomes seen in these trials as well.
Some of the other agents in your list have little evidence either way, as an add-on during radiation. Boswellia, in high enough doses, or in sufficiently bioavailable formulations at lower doses, could help reduce cerebral edema.
Iron supplementation during radiation has mouse evidence, but no human evidence. The caveat about radiosensitizers with no human evidence, is that their safety profiles are unknown.
I think of alkylglycerols primarily as something to take to boost low platelet counts. This (low platelets) is more of a problem with the high dose monthly cycles of TMZ after radiation.
If I were to attempt an extreme carb-restricted diet, such as ketogenic diet, for a limited time period, the six weeks of radiation would be the time I would do it. There is surprising mouse evidence for this combination (ketogenic diet + radiation).
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036197
http://astrocytomaoptions.com/radiation/
DeleteI would consider adding a COX-2 inhibitor such as Celebrex during radiation. COX-2 is a rate-limiting enzyme for the production of prostaglandin E2 (PGE2), and tumors increase production of PGE2 in response to radiation, which increases the invasive behaviour of tumors.
DeleteMany doctors advise against NSAIDs (non-steroidal anti-inflammatory drugs) if the patient is also on dexamethasone, out of concern for damage to the gastro-intestinal lining. I believe this is more of a concern for non-specific COX inhibitors, such as aspirin, ibupfrofen etc. Specific COX-2 inhibitors pose less of a risk for adverse gastro-intestinal side-effects.
I believe Rich started his cocktail in 2007 after his radiation was already completed, so its likely that there was no attention paid to radiosensitizers when he was choosing his cocktail.
ReplyDeleteThanks Stephen!! This is very helpful
ReplyDeleteHi Trent. In case you are interested, I posted my RT cocktail end of last year:
Deletehttp://btcocktails.blogspot.com/2017/12/treatment-options-post-rttmz-phase-for.html
If I did it again, I would probably not take the Disulfiram as it gave me some minor issues with neuropathy at the time. My treatments have been effective so far (I hit my ~12m PFS today), but to be honest it's hard to tell what worked and what hasn't. Simply too many variables in there, but I do feel like my RT cocktail served me well overall.
Good luck with your cocktail!
John
If I did it again I would also add Sulforaphane, personally. It's a very potent phytochemical which in my opinion continues to be underused.I once wrote a brief into here as well:
Deletehttps://btcocktails.blogspot.com/search/label/sulforaphane
It lacks comprehensive studies, but appears to act as a radiosensitizer as well. There are quite a few such studies if to be found if you google it.
Hi, I also posted my mom's cocktail during radiation, a few days ago: https://btcocktails.blogspot.com/2018/08/moms-cocktail.html
ReplyDelete