Wednesday 26 August 2015

when to start tamoxifen

Dear stephen and everyone,
We are now 1 week post radiation..and we r supposed to start ccnu after another 2 weeks..
i am planning to combine ccnu with tamoxifen..and i read that Ben started tamoxifen 2 weeks prior the chemo..

So I am thinking this means we should start tamoxifen now gradually..
what do u think?? Is it safe to start it now with a small dose??

Sarah
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9 comments:

  1. Stephen W27 August 2015 at 13:21

    Sarah,
    According to my unproven theory, IDH1-mutant tumors like your husband's are more sensitive to high-dose tamoxifen than primary GBM. It likely has therapeutic effect even as a single agent.

    One trial of high-dose tamoxifen used the following protocol:

    "Tamoxifen (ICI Pharmaceutical, Wilmington, DE) was
    first administered for 4 days at standard antiestrogen doses (20
    mg p.o. bid.) to observe for any side effects. If tolerated, the
    dose was increased weekly to achieve target dose over a
    I -month period (80 mg bid. in females, 100 mg b.i.d. in males)."

    p.o.= orally
    b.i.d.= twice daily

    http://www.ncbi.nlm.nih.gov/pubmed/9816211

    Major side effect to watch out for with high-dose tamoxifen is blood clots. Ben dealt with this by taking aspirin and long walks. I would be hesitant to combine Celebrex with aspirin, and might instead substitute aspirin for celebrex during the high-dose tamoxifen therapy.

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  2. Stephen W27 August 2015 at 13:23

    And to answer your question, if it were me I would start tamoxifen now using the protocol above (start out for a few days with standard low doses, and increase weekly until reaching the target dose).

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  3. Amber27 August 2015 at 13:40

    Stephen, do you think I should include Temoxifen into my cocktail? I am IDH1 negative

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  4. Stephen W27 August 2015 at 14:32

    Amber, if I recall correctly your tumor tested negative for IDH1 R132H. On the other hand, adult brainstem gliomas (including pontine gliomas) are usually one of two types: either IDH1 mutated or H3F3A mutated. IDH1 mutations in these tumors are often a different variant (for example R132C) that wouldn't be detected by the standard test. In other words your tumor may have been IDH1-mutant, even though it tested negative with the standard test.

    http://astrocytomaoptions.com/genetic-overview-of-brainstem-and-thalamic-gliomas/

    Where do you stand now? Stable disease? Full remission?

    Tamoxifen is something I would consider in your case, though I would want to do more research on potential side-effects to do with anti-estrogenic effects, as a pre-menopausal woman.

    Is there any tumor tissue remaining that could be used for genetic sequencing of the IDH1 gene? Or did you only have a biopsy previously (which means there's probably little tissue available)?

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    Replies
    1. Amber28 August 2015 at 12:53

      You are right, Stephen, IDH1 tested negative but when I went to get second opinion at NIH they basically told me the same thing you just did. There was so little tumor tissue taken that they did not even have enough to test for MGMT. When I inquired about additional tests, they said they did not have enough material for anything else.

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  5. Unknown30 August 2015 at 11:48

    Thank you stephen ( sorry for my late response i had an internet connection problem) i will follow this protocol exactly..i recall u said 100 mg bid for males but this 100 mg should be multiplied by the body surface area..right?
    Also i will replace the celebrex with the aspirin..
    thanks

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  6. Stephen W30 August 2015 at 14:38

    The protocol I quoted above does not multiply those doses by body surface area. 100 mg bid means 200 mg per day total.

    Other trials have used 80-100mg per square meter of body surface. We calculated your husband's body surface to be about 1.85 m2, which would multiply to a total dose of ~150 to 185 mg per day.

    So the dose for your husband could be 150-200mg per day total depending on which protocol you choose to follow.

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  7. Unknown31 August 2015 at 01:34

    Ok gr8 thank you for the clarification

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  8. Anonymous15 May 2016 at 20:55

    Hi Sarah,

    I'm just jumping on to this post. My husband is about to START radiation and I'm researching drugs for him to add after he completes radiation. He'll be taking TMZ afterwards, and I'm exploring the cocktail approach. Did you find Tamoxifin effective as a single agent--or did you combine it with other drugs as well?

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