A phase I and pharmacokinetic study of gemcitabine given by 24-h hepatic arterial infusion
| Autor: | A.C. Laan, C. J. van Groeningen, R. Ruyter, J. M. G. H. Van Riel, Richard J. Honeywell, Lemonitsa H. Mammatas, F.G. van den Berg, G.J. Peters, G. Giaccone |
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| Přispěvatelé: | Medical oncology, Medical oncology laboratory, Radiology and nuclear medicine, CCA - Innovative therapy |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Antimetabolites Antineoplastic Cancer Research medicine.medical_specialty Maximum Tolerated Dose medicine.drug_class medicine.medical_treatment Cmax Deoxycytidine Gastroenterology Antimetabolite chemistry.chemical_compound Hepatic Artery Hepatic arterial infusion Pharmacokinetics Internal medicine medicine Humans Infusions Intra-Arterial Infusions Intravenous Aged Chemotherapy business.industry Liver Neoplasms Middle Aged Thrombocytopenia Gemcitabine Treatment Outcome Endocrinology Oncology chemistry Toxicity Female business medicine.drug |
| Zdroj: | European Journal of Cancer, 45(14), 2519-2527. Pergamon van Riel, J M G H, Peters, G J, Mammatas, L H, Honeywell, R J, Laan, A C, Ruijter, R, van den Berg, F G, Giaccone, G & van Groeningen, C J 2009, ' A phase I and pharmacokinetic study of gemcitabine given by 24-h hepatic arterial infusion ', European Journal of Cancer, vol. 45, no. 14, pp. 2519-2527 . https://doi.org/10.1016/j.ejca.2009.05.025 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2009.05.025 |
| Popis: | This study was performed to assess the toxicities, the maximum-tolerated dose (MTD), the pharmacokinetics and the anti-tumour activity of gemcitabine given by 24-h hepatic arterial infusion (HAI).Patients with liver malignancies received gemcitabine by 24-h HAI, weekly x 3, every 4 weeks. On day 1 or day 8 of the first cycle, patients received one administration by 24-h intravenous infusion for pharmacokinetic comparison and to determine hepatic extraction.Thirteen patients received gemcitabine at the dose levels of 75, 135 and 180 mg/m(2). The MTD was 180 mg/m(2) with thrombocytopaenia as the dose-limiting toxicity. Pharmacokinetic analysis showed a significantly lower maximum gemcitabine plasma concentration (C(max): HAI, 26, 80 and 128 nM, respectively; IV, 229, 264 and 293 nM, respectively) and area under the plasma-concentration-versus-time curve (AUC(0-24h): HAI, 386, 1247 and 2033 nmol x h/L, respectively; IV, 3526, 4818 and 5363 nmol x h/L, respectively) during HAI, compared with intravenous infusion (both P0.001). Additionally, the mean hepatic extraction ratios of gemcitabine at the 75, 135 and 180 mg/m(2) dose level were 0.89, 0.75 and 0.55, respectively. Hepatic extraction decreased linearly with increasing dose. The C(max) and AUC(0-24h) of 2',2'-difluoro-2'-deoxyuridine, the deaminated product of gemcitabine, were similar for HAI and intravenous infusion. Seven patients had stable disease for a median duration of 9 months (range: 2-11 months).Gemcitabine given by 24-h HAI was well tolerated and resulted in significantly lower systemic gemcitabine plasma concentrations than intravenous infusion due to a relatively high hepatic extraction. |
| Databáze: | OpenAIRE |
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