Optimizing TMZ

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Optimizing TMZ


My 64-year-old husband was diagnosed with GBM in his left temporal lobe after a successful resection in 1/2016. His tumor is unmethylated and IDH negative. He is TMZ-naive and has been on Keytruda and Optune for a year. The tumor was stable until late October, when it extended into a new area.  It is slow-growing according to a PET scan yesterday.

Genomic testing of tissue retrieved from a second resection 11/16 highlighted mutations in NF1, PTEN, ASXL1, HNF1A, MLH1, NOTCH1 and SPEN. My husband's NO suggested Temsirolimus because of the PTEN mutation and TMZ starting in January.

My big research question is how to get the most kick out of TMZ, given his methylation status. It seems that either daily or 7-day/alternating Temodar have better clinical results than the standard protocol. I also wondering how best to sensitize GBM cells to TMZ and potentiate the treatment. Different studies suggest adding:
- Tamoxifen
- MGMT inhibitor O6-benzylguanine (O6-BG)
- Interferon-β (IFN-β)
- oncolytic adenovirus
- excision repair pathway enzyme apurinic/apyrimidine endonuclease/redox factor-1 (APE)
- Prozac/Fluoxetine
- antabuse/disulfiram
-Metformin

This all makes my head swim. Have any of you tried an alternative TMZ dosing schedule along with something to enhance its effectiveness against a unmethylated tumor?

Thanks for all your information and help.



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