Monday, 14 November 2016

*Sirolimus and Hydroxychloroquine with TMZ increases survival to a 28 month minimum*

I came across this study and the results looked very promising in comparison to standard of care alone for GBM.  However, the sample size is very small and not statistically significant.  With that said, I still think these results are hard to ignore.  Especially since only 3 of 20 patients used this combination and the minimum survival time of the 3 was 28 months. (this individual also had dosage reduced because of grade 2 fatigue so there may be some dosage dependance)

Results: The median survival time of the 20 patients was 13.7 months (range: 2.2 to 37 months). Surprisingly, the 3 patients who received sirolimus and HCQ as an add-on treatment survived for a longer period of time (median 34 months). Transient grade 3 myelotoxicity and grade 2 fatigues were rapidly resolved by treatment interruption or dose reduction.

These patients were much older so would we interesting to see how this therapy would work in younger patients with stronger immune systems.

From Kwan-Hwa Chi, MD in an email to me: " this regimen works better in mesenchymal type of GBM, the worst prognosis one and multiple recurrent case."

See the below link to investigate

Sirolimus and Hydroxychloroquine as an Add-On to Standard Therapy for Glioblastoma Multiforme: Case Report

8 comments:

  1. I agree these results are hard to ignore. Given the longer-term survival of these 3 patients, I would have liked to see a much more detailed description including MGMT status, EGFR status etc., but alas there is no genetic information given. Their ages were 71, 62, and 69, making IDH1 mutation rather unlikely.

    Patient 3 died at 28 months from diagnosis, and the other two patients seem to have been without disease progression at 34 and >36 months from diagnosis. It would have been fairer to say median survival wasn't reached at a median follow-up time of 34 months (median survival can't be determined when 2 of 3 patients are still alive without progression).

    I'm inclined to believe that this treatment regimen is superior to standard of care for some subgroup of patients. Without any genetic info on these patients (MGMT, EGFR, PTEN etc.) that is a matter of speculation. I would have expected more genetic information to be available for three patients diagnosed in 2013.

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    1. I contacted the authors based in Taiwan to see is they had any genetic information. Hopefully they'll reply.

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    2. From Kwan-Hwa Chi, MD in an email to me: " this regimen works better in mesenchymal type of GBM, the worst prognosis one and multiple recurrent case."

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  2. And special thanks to Michael for bringing this study to our attention. Oddly, it doesn't seem to be on pubmed.

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  3. Interesting. Thanks Michael for sharing. Can someone help me understand the difference between Hydroxy Chloroquine and Chloroquine phosphate? I give my husband chloroquine phosphate since HCQ was not proven to be effective in a previous study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203513/

    Thanks
    Noha

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    1. Chloroquine and hydroxychloroquine are nearly identical, except for the hydroxyl group (one atom each of hydrogen and oxygen) tagged onto the end in the case of hydroxychloroquine. Because of this very minor molecular difference "Hydroxychloroquine is more polar, less lipophilic, and has more difficulty diffusing across cell membranes."

      I wouldn't recommend changing to hydroxychloroquine if you're already using chloroquine. Chloroquine may be superior anyway because of the pharmacokinetics properties quoted above.

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    2. The phosphate part of chloroquine phosphate is relatively unimportant. Most drugs as consumed are in the form of a salt [in the technical sense of the term "salt", not necessarily containing sodium]:

      chloroquine phosphate, hydroxychloroquine sulfate, sildenafil citrate, metformin hydrochloride etc, etc.

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  4. Thanks Stephen .. Really appreciate the help.
    Noha

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