[Efficacy and safety of ixabepilone (BMS-247550), a novel epothilone B analogue].
The epothilones are a new class of non-taxane tubulin polymerization agents obtained by natural fermentation of the myxobacteria Sorangium cellulosum. The cytotoxic activities of the epothilones, like those of the taxanes, have been linked to stabilization of microtubules, but they also have important differences. Among the epothilone family, ixabepilone (BMS247550) is a semisynthetic derivative of the natural product epothilone B. Ixabepilone was evaluated in vivo in a panel of human and rodent tumour models, the majority of which were chosen because of their known, well-characterized resistance to paclitaxel, and seems able to overcome the over-expression of multidrug resistance and to be unaffected by mutations in the beta tubulin gene. The interest of ixabepilone was clinically confirmed in clinical studies of phase II which demonstrated a strong activity at the patients with metastatic breast cancer resistant to taxanes and in patients suffering of other types of chemoresistant tumors.
Villanueva
Cristian
C
Service d'oncologie médicale, CHU, 3, bd Fleming, 25030 Besançon, France. cvillanueva@chu-besancon.fr
Dufresne
Armelle
A
Pivot
Xavier
X
Viel
Erika
E
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004342:Drug Hypersensitivity / Q000209:etiology; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D043823:Taxoids / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
D034261:Epothilones; D043823:Taxoids; D050257:Tubulin Modulators; C430592:ixabepilone; D017239:Paclitaxel; C093788:epothilone B