Thursday, 11 January 2018

Avastin + Irinotecan?

It seems that my mother's tumor (MGMT methylated) did not decrease after radiation therapy + TMZ.
Doctors offer a combination Avastin + Irinotecan.
They say that if TMZ did not help by the time of radiotherapy, then TMZ will not even help with Lomustin!

But I have not seen a single message on this blog about Avastin + Irinotecan combination!
If we use it, what drugs do you recommend adding to increase efficiency?

11 comments:

  1. This study was not encouraging. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362611/

    The Mussella Foundation reports good results with Avastin and Optune. Have the doctors discussed that?

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  2. It's very popular clinical decision in Russia - to use that combination of drugs. I think one have to use this type of drugs combo only for palliative reasons.

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  3. Bevacizumab + irinotecan was a popular combination earlier (several trials reported in the 2008-2010 period), but since the BELOB trial was published in 2014 it has become more common to combine Avastin with lomustine/CCNU in place of irinotecan.

    Continuing the DCA and chloroquine could help combat resistance to Avastin. I'm not aware of anything specific that would help with irinotecan.

    In the BRAIN trial https://www.ncbi.nlm.nih.gov/pubmed/19720927
    BEV + irinotecan gave moderately better progression-free survival outcomes compared to BEV alone, but nearly identical overall survival from recurrence.

    Did the doctor mention BEV + CCNU/lomustine as being a possibility?

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  4. In our sister experience it didn help Avastin + Irinotecan

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  5. Same tumor ... also had no reaction with TMZ+radio. But my tumor shrunk for the 9 months thereafter with Stupp (TMZ) + additional cycles of TMZ + Methadone + Optune.

    Thus, I would disconfirm the opinion of your doctor that it has to help until radio is over.

    Also, normally first MRI after start of radio is at least 6 weeks after radio is over. Otherwise you can not interpret the picture due to the injuries to the tissue following radiotherapy.

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    Replies
    1. Thank you for message! good luck to you!

      Did you have a large tumor after chemoradiotherapy? and why was it? could not be removed or grown so quickly after the operation?

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  6. After your messages, I persuaded the doctor to use the combination Avastin + Lomustine.
    Mom has already received the first dropper Avastin and now we are waiting for the leukocyte count to start Lomustine.

    However, in the comments above it is also written that TMZ can still give a result.
    I am now thinking, maybe after taking Lomustin take 5 days TMZ (as in CeTeg experience) and see the result on MRI in a month? But is it possible to apply TMZ if the mother has already taken Avastin?

    Can we combine CeTeg and a small dose of Avastin (one dropper in 2 weeks - 6 mg / kg / 2 weeks)? The tumor grew very rapidly after surgery, slightly increased after chemoradiotherapy and it is probably necessary to try this combination?

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  7. I really do not know what to do. Tomorrow I must to make a decision. Strange to cancel temozolomid so early, immediately after chemoradiotherapy.
    But the tumor has grown huge for 3 weeks after the operation and has not decreased for the entire course of radiotherapy and temozolomide!

    Perhaps Lomustine will make temozolomide work? MGMT is methylated.

    But Mom already took Avastin's first dropper. And we can not combine everything together: Avastin, Lomustine, Temolosomide .. (I have not seen any such test.

    It is probably better to stop Avastin after the first dropper and try CeTeg protocol?

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  8. "EORTC 26101 provided phase 3 data on the efficacy of bevacizumab in patients with progressive glioblastoma. Adding bevacizumab to lomustine did not confer a survival advantage over lomustine alone but prolonged progression-free survival somewhat."

    So, if the patient starts taking Lomustine, then there's no point in continuing to take Avastin?
    Winning in time to progression is not worth the toxicity, because in Avastin+Lomustine combination overall survival does not improve!

    The only significant reason why I can choose Avastin and Lomustine is an attempt to add angiotensin system inhibitors (only with low dose Avastin).
    https://www.ncbi.nlm.nih.gov/pubmed/28631191

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    1. That quote refers to the trial population as a whole. When you look at the MGMT-methylated subgroup, there is a modest improvement in overall survival when Avastin is added. Median OS 10.35 months versus 12.55 months, hazard ratio = 0.72.

      Also in the BELOB trial survival at 18 months was approximately 30% with the combination, but only approximately 15% for either drug alone (see figure 2 from the 2014 publication).

      Has he had recent bloodwork? What are his neutrophil counts? There is some evidence that a high neutrophil count can predict response to Avastin.
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342600/

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  9. https://www.ncbi.nlm.nih.gov/pubmed/29330749
    Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients.

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