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Friday, 18 September 2015

Withholding temozolomide in glioblastoma patients with unmethylated MGMT promoter

http://neuro-oncology.oxfordjournals.org/content/early/2015/09/14/neuonc.nov198.extract

Will add to the brain tumor Library.

Quote from Hegi and Stupp:

"Together, the data allow the conclusion that alkylating agent chemotherapy is of marginal benefit, if any, for patients with MGMT unmethylated GBM. By continuing to treat the majority of MGMT unmethylated patients with TMZ, we are missing an opportunity to do better."

Keep in mind that this was written by the lead investigators of the 2005 trial that led to TMZ becoming standard of care for newly diagnosed GBM.  The writing is on the wall.  Soon there will be two standards of care for ndGBM based on MGMT status.  It make take a few years, but patients with unmethylated MGMT status deserve something better.

However, this editorial did not consider the potential to sensitize these tumors to TMZ using agents that inhibit MGMT, or the potential of metronomic schedule TMZ in cases with EGFR overexpression. I wouldn't suggest abandoning TMZ altogether for these patients, but the current protocol does need to be tweaked for these patients (obviously).
at

3 comments:

  1. Unknown22 July 2017 at 12:35

    Hi Stephen! English is not my first (or second) language so I'm not sure if I'm getting everything right. My dad's tumor is IDH1-, P53+, EGFR+. Can you tell the MGMT status from that? And what are the agents that inhibit MGMT? Temozolomide didn't work for my dad last year but now he has to start that again since there is no other options available in Finland. -Anna-Emilia

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    Replies
    1. JuhaH23 July 2017 at 02:06

      Hi Anna-Emilia,
      I'm in similar situation with my relative in Finland. Maybe we could share our experiences. My email: vkalle455@gmail.com.

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    2. Stephen W23 July 2017 at 15:02

      Hi Anna-Emilia,
      No, none of those other markers can predict MGMT status.

      In a small study of 4 GBM patients undergoing a repeat resection within 7-14 days of their original resection, and not treated with anything except for Keppra (levetiracetam) 500-1000 mg twice daily for seizure control, MGMT protein levels were reduced in the tissue from repeat resections (after ongoing Keppra treatment).

      See figure 6 of this study:
      https://www.ncbi.nlm.nih.gov/pubmed/20525765

      There are some other agents with only preclinical (mouse) evidence for reducing MGMT expression or activity, including fluoxetine (Prozac) and disulfiram.

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550181/
      https://www.ncbi.nlm.nih.gov/pubmed/24193513

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