Saturday, 6 August 2016

CUSP-ND and Prozac

Stephen, I recently re-read the paper on CUSP-ND at:

and am a bit concerned at all of the "severe" interactions between Prozac and all of the other drugs in the cocktail (starting on page 104). Particularly it's interaction with celebrex and chloroquine.

My questions are:

  1. If you had to choose between prozac and chloroquine, which would you choose? 
  2. Moreover, I note that in Kast's CUSP9, he utilizes Zoloft (Sertraline) instead. Was there a reason that the CUSP-ND swapped out zoloft for prozac?
  3. Would one be more beneficial than the other if Optune is also utilized along with the protocols?


  1. The red flags raised by drug interaction databases should be regarded as areas of potential concern, but sometimes this is not based on any actual evidence of interaction between the specific drugs. Drugs are grouped into categories in these databases and whenever a drug from category A has a potentially problematic interaction with a drug from category B, then any drug in category A will be said to have a potential interaction with any drug from category B. I know of doctors who prescribe combinations routinely without problem, which would have been contra-indicated according to these computerized databases. While the warnings given by databases should not be ignored, they should be "taken with a grain of salt". Sometimes the warnings are very valid and should be adhered to, other times not so much.

    The database claims that both chloroquine and fluoxetine (Prozac) both might raise the QT interval and thus increase the risk of cardiac arrhythmias.

    Elsewhere in the CUSPND document (page 89) we explain that the actual problem was with the drug citalopram (another SSRI antidepressant), but the database considers all SSRI to be equivalent as far as interactions.

    Patients in both the CUSP9 as well as the proposed CUSPND trial will be carefully monitored in hospital throughout the drug initiation and dose escalation, and that monitoring will include electrocardiograms.

    I suppose if I had to choose though I would choose chloroquine during radiation and chemotherapy, and Prozac after the completion of standard of care, though Prozac would also be tempting during chemotherapy if one's tumor MGMT status is unmethylated, as the drug could downregulate MGMT expression in a mouse model of GBM.

    2. Both drugs were under discussion, in the end we chose Prozac because of superior evidence for GBM: one orthotopic GBM mouse model and one subcutaneous GBM mouse model. Zoloft (sertraline) has yet to undergo in vivo testing for GBM to my knowledge.

    3. One can theorize, but this question is really impossible to answer without experimentation. The first step would be to use the in vitro version of Tumor Treating Fields ( in a lab with GBM cells and add in clinically achievable concentrations of various drugs. However this would not capture the immune effects of drugs and immune-related interactions with Optune, which appears to be an inducer of immunogenic cell death.

    1. As always, a complete answer.

      So much so, in fact, that I'm re-examining exactly what we're giving her.

      Note that we have had chloroquine for some time now but I'm reluctant to give it to her since she already has a rather severe vision cut and I'm afraid to give her anything that might exacerbate that issue.

  2. Hi Logan,

    For the past 18 months I have been taking Prozac 20mg once daily, Celebrex 200mg twice daily, and Chloroquine 250mg once daily along with other cocktail medications and supplements. I was diagnosed 11/2014 with GBM4 in the occipital lobe and have a significant central vision cut. To date I have not had any increased vision loss. I have an eye exam by an ophthalmologist annually.

    I have fully disclosed and discussed my cocktail medications and supplements with my primary NO, as well as other NOs that I have consulted with over the past year and have not been told to discontinue any medications or supplements.

    Also, this is just my personal opinion/experience but I think every patient diagnosed with GBM should be prescribed an antidepressant from "day one". Psychologically this diagnosis is just so devastating that I really think the medical community is doing a disservice by not proactively prescribing an antidepressant from the get-go. I had never even had any depression in my lifetime until I was diagnosed with GBM. I sought out Prozac as part of putting together a drug cocktail. I discovered a secondary benefit was that it helped with the depression stemming from the GBM diagnosis...imagine that! Needless to say, I think that Prozac has important anti-depressant/mental health benefits that equal (or perhaps even surpass) the cocktail component benefit.

    And by the way, the research and time you put in to help your wife get the best possible care is very inspiring- keep up the great posts! :)

    All the best to you and your family,
    Mike B.

    1. Thanks so much for the information and kind words! Still trying to figure out what's the optimal thing for her but this was super helpful.