A Chinese study just published shows that in a U87 GBM mouse model, mice given intravenous disulfiram alone had only minor therapeutic benefits, while the mice given intravenous disulfiram plus copper (by stomach) had significantly increased therapeutic benefit, including reduced microvessel density and tumor volume (see figure 8). I've uploaded this study to the Brain Tumor Library.
There has been considerable debate whether additional copper beyond what is already in the stomach or bloodstream is required to potentiate the anti-cancer effect of disulfiram. Several mouse studies including the one above have shown that orally delivered copper in mice increases the therapeutic effects of disulfiram. The original CUSP9 protocol has dosing information on copper gluconate.
Please note that the addition of copper likely also increases the risk of unwanted side-effects such as peripheral neuropathy (see second study below).
Copper improves the anti-angiogenic activity of disulfiram through the EGFR/src/VEGF pathway in gliomas
N,N-Diethyldithiocarbamate Produces Copper Accumulation, Lipid Peroxidation, and Myelin Injury in Rat Peripheral Nerve
Both of these studies may be found in the Library.
Stephen, I am still confused if disulfiram should be taken only during chemo or all the time. Reading about the drug it seems to me that it is effective as a single agent even without tmz.
ReplyDeleteThe tumor is unmethylated. Should we take it all the time?
You are correct that disulfiram could be effective on its own (without chemotherapy). I would take it every day, unless neuropathy were to become a problem. If neuropathy occured I would stop taking it until the symptoms resolved, and then possibly restart with a less continuous schedule, for example alternate weeks, or only during chemotherapy. Also be aware that DCA can also cause peripheral neuropathy.
ReplyDeleteI checked the dosage of copper in the oryginal CUSP9 and it is 2mg of copper for 250 mg of disulfiram. I am wondering if anybody is eating already?
ReplyDeleteHi Anna, we are planning to add my wife cocktail both, will let you our experience.
ReplyDeleteSo my brother was adding copper but now I see that some places say that it is unsafe to supplement with copper. Is anybody else using it or only my brother? Below is a text from some article" The human body needs copper to properly utilize zinc, so zinc supplementation will yield poor results during a time of copper deficiency. Unfortunately, it is unsafe to supplement with copper directly. It is far too easy to overdose and to cause serious liver problems with direct copper consumption. There are unscrupulous individuals who sell colloidal copper for internal consumption on the Internet, but we warn you to beware of such scoundrels. You will find them astroturfing Internet forums with miraculous stories, and stories are just what they are. The safe way to supplement with copper is to get it indirectly through chlorophyll supplements. Chlorophyll contains enough copper to make a huge difference, and it includes compounds that work with the copper for its best utilization. It is virtually impossible to get an overdose through chlorophyll, and it helps health in many other ways."
ReplyDeleteJeremy is taking 4 mg copper with disulfiram. The safe upper limit for an adult is 10 mg CU daily. That seems high to me and I would not want to take that high a dose daily for a long period of time. Typically a ratio of 1 mg CU to 15 mg Zinc is recommended. But that is for routine supplementation, and even that ratio is debated. Therapeutic dosing is a different situation. Seems to me 4 mg daily with disulfiram would not be a problem. My opinion anyway
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