A combination therapy consisting of the prodrug tretazicar and the enzyme co-substrate caricotamide with potential antineoplastic activity. In the presence of separately and simultaneously administered caricotamide, tretazicar is converted to the short-lived cytotoxic DNA cross-linking agent dinitrobenzamide by NAD(P)H quinine oxidoreductase 2 (NQO2), resulting in the inhibition of DNA replication and the induction of apoptosis. NQO2 has been found to be elevated in certain cancers such as hepatocellular carcinoma (HCC).