The new anti-
cancer drug zilascorb(2H) has shown promising activity in preclinical models. Its putative mechanism of action is reversible
protein synthesis inhibition and long-term treatment is required. As a clinical treatment modality, long-term daily
zilascorb(2H) infusions, as used in previous studies, are not regarded feasible. Therefore, an oral formulation of the
drug was developed, and pharmacokinetic profile, toxicity and antitumor activity of
zilascorb(2H)
tablets were studied. Thirteen patients with advanced solid
cancer not amenable to established
therapy, but with adequate performance status and organ functions, were included. The treatment was given as a daily i.v.
zilascorb(2H) infusion for 5 days, followed by
zilascorb(2H)
tablets twice daily for 3 months. Blood and urine sampling was performed when estimated plasma steady-state level was reached for each formulation, respectively. Analyses of
drug concentrations in plasma and urine were performed by high performance liquid chromatography.
Zilascorb(2H) in
tablet formulation had a bioavailability of 32%, was quickly absorbed and slowly eliminated. Concomitant use of the H2-blocker
ranitidine possibly enhanced bioavailability.
Zilascorb(2H) was well tolerated. Two patients experienced
drug-related
fever, disturbing the treatment schedule for one of them. Moderate
nausea was reported. One objective response was obtained. The bioavailability of
zilascorb(2H)
tablets was satisfactory. The principle of
oral administration of
zilascorb(2H) is feasible for long-term treatment and the side effects are acceptable. The mechanisms of action and the very low toxicity of the
drug makes it a candidate for combination with other
anticancer agents.