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Monday, 1 January 2018

CLOVA cocktail - Your opinion?


It was published in February 2017:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410264/
"The patients treated with CLOVA cocktail in combination with TMZ showed increased survival compared to the control group treated with TMZ alone."

 CLOVA cocktail:
TMZ + 800 mg cimetidine, 400 mg lithium, 10 mg olanzapine, 800 mg valproate.

 Perhaps one of these drugs (to inhibit the activity of GSK3β) can be replaced with more effective?
at

5 comments:

  1. Stephen W2 January 2018 at 16:47

    Thanks Semyon, this is a really interesting study. I remember an abstract report of this cocktail from one of the conferences several years ago, but I hadn't seen the full paper before. This looks promising, with decreased nestin, and decreased proliferation and increased survival seen in both the mouse model as well as the human trial.

    11.2 months median survival from first recurrence is about what I'm used to seeing in clinical trials for recurrence including patients only with KPS 70 or higher, and median KPS 80-90. It's unexpected to see that kind of median survival for patients with much lower KPS (median 50, range 20-50) and RPA class of 7. These were seven patients with very poor prognosis, and all had at least disease stabilization with the CLOVA + TMZ protocol.

    In short this was a very interesting study, and this should be definitely be tested in larger clinical trials. Fortunately, "large multicenter clinical
    trial is currently in progress to validate the efficacy and
    safety of CLOVA cocktail in combination with TMZ, and
    best combination of the drugs composed of the cocktail in
    patients with recurrent GBM."

    ReplyDelete
  2. Semyon18 January 2018 at 11:51

    It is interesting in which form was taken 400 mg lithium?

    Safe food additives contain too little Lithium:
    https://www.iherb.com/pr/Solaray-Lithium-Aspartate-5-mg-100-Capsules/18946
    https://www.iherb.com/pr/KAL-Lithium-Orotate-5-mg-60-Veggie-Caps/70121

    By the way, taking Lithium can cause hypothyroidism, which is artificially induced in one of the treatment options (suppression of T4)
    "The incidence of hypothyroidism is six-fold higher in people on lithium as compared to the general population."
    https://en.wikipedia.org/wiki/Lithium_(medication)

    I also found "Lithium carbonate filmcoated tablets 0,3 g"
    For adults, the dose is 300-600 mg 3-4 times / day.
    Probably, this is it ?

    ReplyDelete
    Replies
    1. Stephen W18 January 2018 at 15:20

      FDA label for lithium carbonate:
      https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017812s027,018421s025,018558s021lbl.pdf

      Delete
  3. Semyon18 January 2018 at 22:54

    Interestingly, will not lithium, like copper, interact with Disulfiram?

    ReplyDelete
    Replies
    1. Stephen W19 January 2018 at 10:33

      In terms of its ability to chelate metals, I've never seen any reports of this kind of interaction with disulfiram and lithium.

      "This complex is formed in order to stabilize metal ions with unusually high or low oxidation states like copper (II), iron (III), cadmium (II), and zinc (II)"
      https://www.omicsonline.org/open-access/repositioning-an-old-antialcoholism-drug-disulfiram-as-a-selectiveeffective-and-economical-anticancer-agent-2329-6631-1000e147.php?aid=74139

      "Formation of such a DSF-metal complex can stabilize the corresponding metal ions which have unusually high or low oxidation states, e.g., Copper (II), Iron (III), Cadmiun (II), and Zinc (II)"
      https://www.ncbi.nlm.nih.gov/pubmed/29065820

      Delete