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.