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Title : Mislav's (netopoloit) Radiotherapy coctail
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Mislav's (netopoloit) Radiotherapy coctail

I've been following this blog for a while but since I haven't introduced myself yet here's a short backstory.

In July 2018 I was diagnosed with grade II astrocytoma in right precentral gyrus. I had a subtotal resection in October 2018, leaving some tumor tissue that was too close to corticospinal tract. Basic immunohistochemistry tests revealed the presence of GFAP and IDH (R132H), p53, ATRX mutations in resected tumor tissue.

My oncologist considers my tumor to be "high-risk" because of subtotal resection, me being close to 40 years old and, most importantly, the tumor tissue consisting of about 10% gemistocytic astrocytes. Because of this, we decided to start adjuvant therapy as soon as possible.

I should be starting radiotherapy in about a month (PCV chemo will be done later, separately).

I did a lot of research and this blog was a precious resource. I recently decided on a cocktail of medications and supplements to take during radiotherapy and would greatly appreciate any comments and suggestions on what else to include or what to exclude from the list.

This is a cocktail I intend to use during radiotherapy. I plan to use different cocktail later with chemo.

Important note: some of the points in "Reasoning" column may be based on weak evidence or may be speculative claims extracted from different sources. I didn't have time to compile all the sources of the information but if there are any specific questions in comments I'll be happy to post any additional links or papers.

List of Rx drugs:

Name	Reasoning	Note
Acetazolamide	possible radiosensitizer; carbonic anhydrase II (CAII) inhibitor.
Alfacalcidol	promotes redifferentiation; hedgehog pathway inhibitor.
Auranofin	increases ROS; inhibition of PI3K/AKT/mTOR axis; inhibition/reduction of TNF, IL-6, CRP;,inhibiton of phosphofructokinase.
Celecoxib	edema control; COX-2 inhibitor; PGE2 inhibitor; carbonic anhydrase 9 (CAIX, CA9) inhibitor; suppresses Wnt/β-catenin signaling.
Metformin
Minocycline	PARP inhibitor; inhibits MMP-2 and MMP-9; modulates phenotype of microglia; disrupts CCL2 chemokine signaling; STAT3 inhibitor; NF-κB inhibitor; MAPK pathway inhibitor; hypoxia inducible factor 1 alpha (HIF-1α) inhibitor; Akt/mTOR pathway inhibitor.
Sodium phenylbutyrate	Histone deacetylase inhibitor (HDACi); c-myc inhibitor; urokinase inhibitor.
Disulfiram	increases ROS; possibly synergistic with Auranofin?; proteasome inhibitor; NF-κB inhibitor.
Memantine	possible reduction of radiation-induced neurocognitive decline ?
Perillyl alcohol	direct cytotoxicity; possibly reduces endothelial-tomesenchymal transition; mTOR inhibitor; Ras inhibitor; G1 cell cycle arrest ?
Prazosin	limited evidence of direct cytotoxicity to glioma initiating cells;
Tamoxifen		Still just considering use during radiotherapy. May be rendered useless by Celecoxib, a potent CYP2D6 inhibitor; Will be used during and after PCV.
Ibudilast (MN-166)		Just considering; No concrete evidence for use during radiotherapy. Limited evidence of benefits when used with chemo.
Itraconazole	Hedgehog pathway inhibitor	Not high on the list because of CYP450 interactions.
Mebendazole		Will probably skip this one for now because of no evidence of benefits in combination with RT, also low bioavalibility.

List of supplements:

Name	Reasoning	Note
Boswellic acids	edema control	Downside: non-selective inhibitor of the major drug metabolising CYP enzymes 1A2/2C8/2C9/2C19/2D6 and 3A4 in vitro.
Glucans / PSK / mushroom extracts
Guduchi (Tinospora cordifolia) extract	limited evidence of guduchi as differentiation agent and radiosensitizer
Honokiol (Magnolia bark, Houpu)	autophagy promotor; enhances ROS production;
Omega 3 / DHA		High DHA/EPA ratio
Pterostilbene	possible radiosensitizer
Sulforaphane	possible radiosensitizer
Tetrandrine (from Stephania Tetrandra)	Wnt/β-catenin inhibitor; possible radiosensitizer.
Cannabis	possible radiosensitizer
Epigallocatechin-3-gallate (EGCG) [from green tea extract]	possible radiosensitizer
Garlic	increases ROS; NF-κB inhibitor; HDAC inhibitor at high doses;
Luteolin	increases ROS; NF-κB inhibitor;
Melatonin
Propolis
Silibinin (active component of silymarin from milk thistle)		low dose during radiotherapy - could reduce ROS?

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