Preclinical pharmacology of BMS-275183, an orally active taxane

Citation
Wc. Rose et al., Preclinical pharmacology of BMS-275183, an orally active taxane, CLIN CANC R, 7(7), 2001, pp. 2016-2021
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
7
Year of publication
2001
Pages
2016 - 2021
Database
ISI
SICI code
1078-0432(200107)7:7<2016:PPOBAO>2.0.ZU;2-P
Abstract
EMS-275183 is a taxane, the mechanism of action of which is like other know n taxanes, and is the polymerization of tubulin, BRIS-275183 given p.o. was as effective as i.v. paclitaxel in five tumor models [murine M109 lung and C3H mammary 16/C, and human A2780 ovarian (grown in mice and rats) and HCT /pk colon]. It was active in one other tumor model (human HCT-116 colon) bu t inferior to parenteral paclitaxel, EMS-275183 given p.o. was active in a human, hormone-dependent, prostate tumor model, CWR-22, and just as effecti ve as anti-androgen chemotherapy, In a schedule dependency study, increasin g the interval of time between oral administrations resulted in greater cum ulative dose tolerance and improved therapeutic outcome, Oral BRIS-275183 w as evaluated as a combination therapy in conjunction with i.v. paclitaxel, Therapeutic advantages were evident for tumor-bearing mice that received th e oral taxane either after induction chemotherapy or between courses of suc h treatment. BMS-275183 is currently in Phase I clinical trials at multiple sites.