British Journal of Cancer (2013), 1 | doi: 10.1038/bjc.2013.18 | Letter to the Editor | 22 January/5 March 2013
1Department of Cell Biology & Genetics, Palacky University, Olomouc, Czech Republic
I have read the article on anticancer activity of an old anti-alcoholism drug disulfiram published in this Journal (Liu et al, 2012) with great interest.
In this Letter to the Editor, I would like to stress that we already have clinical evidence for disulfiram anticancer activity. One molecule of disulfiram is cleaved, even as early as in the stomach, to two molecules of ditiocarb, which forms the copper complex in the body (Johansson, 1992).
About 20 years ago, Dufour et al (1993) published encouraging results of phase II placebo-controlled clinical trial of ditiocarb (diethyldithiocarbamate) in 64 women with high-risk breast cancer. After 6 years, overall survival was 81% in ditiocarb group vs 55% in placebo group. The authors used (for 70 kg woman) 700 mg of sodium ditiocarb (∼600 mg of ditiocarb itself) dosing per week. However, the trial has been forgotten and the authors did not realise that ditiocarb is a main metabolite of disulfiram.
The standard dosing of disulfiram today is 250–500 mg per day and was even as high as 3000 mg per day (Suh et al, 2006). Arguably, breast cancer patients on higher doses of disulfiram may experience much more remarkable benefit than it was shown in Dufour et al (1993) trial. In public interest, we urgently need new phase III clinical trials of disulfiram in breast cancer patients to repurpose the cheap (1-year long therapy costs approximately US$550) and safe drug for breast cancer (Cvek, 2012). Moreover, we already have evidence from a case report that disulfiram is able to cure patient with bone (spine, ribs, pelvis) metastases from breast cancer (Lewison, 1977).
According to the article by Liu et al (2012) and after successful trials for breast cancer, disulfiram might be used for the treatment of brain tumours (a) and even other cancers (Cvek, 2011).
Cvek B (2011) Targeting malignancies with disulfiram (Antabuse): multidrug resistance, angiogenesis, and proteasome. Curr Cancer Drug Targets 11: 332–337.
Cvek B (2012) Nonprofit drugs as the salvation of the world’s healthcare systems: the case of Antabuse (disulfiram). Drug Discov Today 17: 409–412.
Dufour P, Lang JM, Giron C, Duclos B, Haehnel P, Jaeck D, Jung JM, Oberling F (1993) Sodium ditiocarb as adjuvant immunotherapy for high risk breast cancer: a randomized study. Biotherapy 6: 9–12.
Johansson B (1992) A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites. Acta Psychiatr Scand Suppl 369: 15–26.
Lewison EF (1977) Spontaneous regression of breast cancer. Prog Clin Biol Res 12: 47–53.
Liu P, Brown S, Goktug T, Channathodiyil P, Kannappan V, Hugnot JP, Guichet PO, Bian X, Armesilla AL, Darling JL, Wang W (2012) Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br J Cancer 107: 1488–1497.
Suh JJ, Pettinati HM, Kampman KM, O’Brien CP (2006) The status of disulfiram: a half of a century later. J Clin Psychopharmacol 26: 290–302.