Monday, 4 February 2019

Drugs to Combine with CCNU

My husband will soon begin CCNU for recurrence. In reviewing Ben Williams' document, I see that Verapamil and Calcium Channel Blockers like nimodipine have some evidence for augmentation benefit; however, the articles I found (both from his references and my own search) are quite old. Verapamil has more drug interactions than nimodipine. Is there any research about these drugs or other potential augmenters which I might share with his NO? (His NO has generally been supportive of repurposed drugs when I can share relevant studies. His NO does not want to combine CCNU with TMZ despite CeGaT study due to increased toxicity.)

Much gratitude and well wishes to all--
S.

2 comments:

  1. The data for nimodipine is in vitro, the least reliable level of evidence.

    For verapamil, there is rodent evidence for better tumor control when combined with BCNU (a close chemical relative of CCNU), in a subcutaneous glioma model. Although this wasn't an orthotopic model (the brain tumor cells were transplanted into the flank, not into the brain), it still trumps in vitro evidence because it shows that verapamil at physiologically achievable levels can have this chemosensitizing effect in combination with BCNU.

    http://sci-hub.tw/https://doi.org/10.3171/jns.1990.73.2.0248

    In contrast, many in vitro studies use drug concentrations that aren't physiologically achievable.

    There is also some human evidence to support verapamil in other types of cancer.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968472/

    I'm sure his doctor would want to check his baseline blood pressure before starting him on a drug such as verapamil, but given the experimental evidence and the limited clinical evidence, I would certainly experiment with the verapamil + CCNU combo. Ben was doing 7 days of verapamil surrounding his CCNU or BCNU days (3 days before, the day of, and 3 days after).

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    Replies
    1. Stephen--
      Many thanks for your thoughtful reply. Your understanding of the literature is invaluable and your generosity in sharing your knowledge is boundless. I have just emailed his NO.

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