Friday, 21 April 2017

Questions about Celebrex and Tamoxifen

Hi,


I am new to agents of GBM. I have following questions


1) Is it necessary or beneficial to take Celebrex in the periods between chemotherapy(TMZ) cycles?


2) We also want to add Tamoxifen to my mother's cocktail list, But we are not sure if it will be effective.


3)One study article tells me that adding folic acid will be helpful to change MGMT from unmethylated status to methylated status, Is that correct?


It would be greatly appreciated if you could share your knowledge or information about these questions.


Stephen, Would you like to help me?


Best Regards
James Zhou



2 comments:

  1. I believe that a COX-2 inhibitor like Celebrex is especially important during and following radiation, as one of the ways the tumor responds to radiation is by increasing prostaglandin E2 (PGE2) production making the tumor cells more invasive and increasing immunosuppression. COX-2 is an important enzyme in the PGE2 production pathway, and blocking it is especially important during this period.

    There have been many clincial trials of tamoxifen for high grade glioma, but none of them have been that conclusive in my view. One trial in China showed tamoxifen + radiation was comparable in efficacy to TMZ + radiation, but the majority of patients in this trial had grade 3 gliomas, not GBM. In a different study, for recurrent GBM, there was a 20% response rate to tamoxifen alone, suggesting tamoxifen will have some benefit in a subset of GBM patients.
    https://www.ncbi.nlm.nih.gov/pubmed/9816211

    Folic acid, after being metabolized to 5-MTHF, can participate in overall DNA methylation. This is because 5-MTHF is an essential co-factor for remethylating homocysteine to methionine, and methionine ultimately provides the methyl groups for DNA methylation. This is the basis for clinical trials such as this one:
    https://clinicaltrials.gov/ct2/show/NCT01700569

    "In preclinical models, it has been demonstrated that MGMT methylation (which is silencing the DNA repair process) is achievable by folic acid"

    I've not seen any data published from this trial, so whether this would work in humans is unknown. Increasing overall DNA methylation in a non-targeted way could have many unpredictable effects on the tumor beyond simply influencing MGMT expression.

    Levetiracetam (Keppra) has actually been shown to reduce MGMT expression in 4 patients at standard anti-seizure doses, and fluoxetine (Prozac) has also reduced MGMT expression in preclinical models.

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  2. Stephen:

    Thanks Again

    James Zhou

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