1.Effect of food on the pharmacokinetic behavior of the potent oral taxane BMS-275183.
Bröker LE1, Valdivieso M, Pilat MJ, Deluca P, Zhou X, Parker S, Giaccone G, Lorusso PM. Clin Cancer Res. 2008 Jul 1;14(13):4186-91. doi: 10.1158/1078-0432.CCR-07-4594.
PURPOSE: BMS-275183 is a potent oral paclitaxel analogue that previously showed promising activity. The goal of the present trial was to investigate whether food affects the pharmacokinetics of BMS-275183. Additionally, we evaluated its pharmacokinetic variability using flat-fixed dosing compared with dosing individualized by body surface area (BSA).
2.A phase 1 study of BMS-275183, a novel oral analogue of paclitaxel given on a daily schedule to patients with advanced malignancies.
Heath EI1, Lorusso P, Ramalingam SS, Awada A, Egorin MJ, Besse-Hamer T, Cardoso F, Valdivieso M, Has T, Alland L, Zhou X, Belani CP. Invest New Drugs. 2011 Dec;29(6):1426-31. doi: 10.1007/s10637-010-9498-z. Epub 2010 Aug 3.
PURPOSE: BMS-275183 is an oral C-4 methyl carbonate analogue of paclitaxel that has the same mechanism of action, stabilization of tubulin polymerization. The present study was designed to: (i) assess the safety and tolerability of BMS-275183, and (ii) determine a suitable Phase II dose of BMS-275183 when given on a continuous daily schedule to patients with advanced solid tumor(s).
3.Metabolism and excretion of an oral taxane analog, [14C]3'-tert-butyl-3'-N-tert-butyloxycarbonyl-4-deacetyl-3'-dephenyl-3'-N-debenzoyl-4-O-methoxy-paclitaxel (BMS-275183), in rats and dogs.
Ly VT1, Caceres-Cortes J, Zhang D, Humphreys WG, Ekhato IV, Everett D, Cömezoğlu SN. Drug Metab Dispos. 2009 May;37(5):1115-28. doi: 10.1124/dmd.108.025809. Epub 2009 Feb 5.
3'-tert-Butyl-3'-N-tert-butyloxycarbonyl-4-deacetyl-3'-dephenyl-3'-N-debenzoyl-4-O-methoxy-paclitaxel (BMS-275183) is a taxane analog that has the potential for oral use in the treatment of various types of cancer. In this study, the metabolism and excretion of [(14)C]BMS-275183 were evaluated after a single oral administration of [(14)C]BMS-275183 to rats and dogs (15 and 1 mg/kg, respectively). To aid metabolite identification by mass spectrometry (MS), a stable labeled (phenyl-(13)C(6)) BMS-275183 was included in 1:1 ratio of (13)C(6)/(12)C in the dose administration. Fecal excretion was the major route of elimination for [(14)C]BMS-275183 in both species (85-86 and <9% of the dose in feces and urine, respectively). The highest radioactivity in plasma was observed at 1 h postdose, suggesting rapid absorption of the drug in both species. The total radioactivity in plasma was measurable up to 24 h postdose. Metabolites were identified by liquid chromatography-MS and/or NMR spectroscopy.
4.Phase I trial with BMS-275183, a novel oral taxane with promising antitumor activity.
Bröker LE1, de Vos FY, van Groeningen CJ, Kuenen BC, Gall HE, Woo MH, Voi M, Gietema JA, de Vries EG, Giaccone G. Clin Cancer Res. 2006 Mar 15;12(6):1760-7.
PURPOSE: BMS-275183 is an orally administered C-4 methyl carbonate analogue of paclitaxel. We did a dose-escalating phase I study to investigate its safety, tolerability, pharmacokinetics, and possible antitumor activity.