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OGT 719 (Oxford GlycoSciences, Abingdon, UK) is a novel nucleoside analogue with a galactose molecule attached to a fluorinated pyrimidine. OGT 719 has the capacity selectively to bind to asialoglycoprotein receptors that are found exclusively on hepatocytes and hepatocellular carcinoma (HCC) cells. The aim of this study was to establish the safety and to examine the pharmacokinetics of this novel compound in patients with liver cancer. Fourteen patients received a total of 37 cycles of OGT 719 at four dose levels ([500 mg/m2 first cycle, 1 000 mg/m2 subsequent cycles], 1000 mg/m2, 3 300 mg/m2 and 7500 mg/m2). OGT 719 was administered as a 3-h intravenous infusion in a 250 ml saline solution, daily for 5 days every 4 weeks. Pharmacokinetic parameters were studied during the first cycle of dose levels 1 and 2 (500 mg/m2. and 1 000 mg/m2, respectively). The maximum plasma concentration was attained within 5 min of completing the infusion and almost doubled, dose dependently, with a doubling of the infused dose. The plasma level declined rapidly in a monophasic manner with an elimination half-life of 2.1 and 2.5 h for dose level 1 and 2, respectively The mean area under the curve (AUC(o - infinity) area under the curve to 24 h; AUC(o - infinity), area under the curve to infinity) doubled at the higher dose level. None of the patients had a significant tumor response. Elimination half-life of OGT 719 by 3-h intravenous infusion is short and monophasic. Toxicity was minimal at the highest dose level.

Type

Journal article

Journal

Acta Oncol

Publication Date

2004

Volume

43

Pages

245 - 251

Keywords

Aged, Antineoplastic Agents, Carcinoma, Hepatocellular, Drug Evaluation, Female, Fluorouracil, Humans, Infusions, Intravenous, Liver Neoplasms, Male, Maximum Tolerated Dose, Middle Aged