Several months ago, Dr Nechushtan from Israel published the 1st clinical trials regarding the Disulfiram in the treatment of non-small cell lung cancer. This is a phase 2 randomized double-blind clinical study. In this study, disulfiram was given in combination with conventional chemotherapy for stage IV non-small cell lung cancer. Disulfiram was administered at a dose of 40 mg three times daily. Forty patients were treated for more than two cycles, half with and half without disulfiram, which was well tolerated. An increase in survival was noted for the experimental group (10 vs. 7.1 months). Interestingly, there were only two long-term survivors, both in the disulfiram group. The authors concluded that addition of disulfiram to a combination regimen of cisplatin and vinorelbine was well tolerated and appeared to prolong survival in patients with newly diagnosed non-small cell lung cancer.
Disulfiram, an alcohol aversion agent, has been in use clinically for alcoholism for >50 years. It targets cancer stem-cell which express aldehyde dehydrogenaseALDH1, an enzymes involved in alcohol detoxification process. disulfiram can induce apoptosis in pancreatic cancer stem cells expressing high levels of aldehyde dehydrogenase. Many lab studies show an anticancer effect of this drug in vitro and in mouse models. Preclinical studies have suggested that disulfiram also possesses antiangiogenic activity.
It is extremely rare to see long-term survivors beyond the 3 years in patients with stage IV lung cancer treated by chemotherapy alone. The presence of long-term survivors in the Disulfiram only group suggests that it does have the anti cancer stem-cell activity and hence eliminate the chemotherapy resistant subclones of cancer stem cells which are responsible for recurrence. It is important to note that the difference in survival continued after cessation of chemotherapy and maintenance with disulfiram alone.
The drug is inexpensive, and its tolerability and safety have been demonstrated over years of clinical experience with a large number of patients.