ZILASCORB(H-2), A NEW REVERSIBLE PROTEIN-SYNTHESIS INHIBITOR - CLINICAL-STUDY OF AN ORAL PREPARATION

The new anti-cancer drug zilascorb(H-2) has shown promising activity i n preclinical models. Its putative mechanism of action is reversible p rotein synthesis inhibition and long-term treatment is required. As a clinical treatment modality, long-term daily zilascorb(H-2) infusions, as used in previous studies, are not regarded feasible. Therefore, an oral formulation of the drug was developed, and pharmacokinetic profi le, toxicity and antitumor activity of zilascorb(H-2) tablets were stu died. Thirteen patients with advanced solid cancer not amenable to est ablished therapy, but with adequate performance status and organ funct ions, were included. The treatment was given as a daily i.v. zilascorb (2H) infusion for 5 days, followed by zilascorb(H-2) tablets twice dai ly for 3 months. Blood and urine sampling was performed when estimated plasma steady-state level was reached for each formulation, respectiv ely. Analyses of drug concentrations in plasma and urine were performe d by high performance liquid chromatography. Zilascorb(H-2) in tablet formulation had a bioavailability of 32%, was quickly absorbed and slo wly eliminated. Concomitant use of the H-2-blocker ranitidine possibly enhanced bioavailability. Zilascorb(H-2) was well tolerated. Two pati ents 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(H-2) tablets was satis factory. The principle of oral administration of zilascorb(H-2) is fea sible 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.