Patupilone (epothilone B, EPO906) inhibits growth and metastasis of experimental prostate tumors in vivo.
BACKGROUND
Microtubule agents appear promising for the treatment of prostate cancer. Patupilone (epothilone B), a highly potent non-taxane microtubule stabilizing agent, was evaluated in models of androgen-independent prostate cancer.


METHODS
Patupilone was administered to athymic mice bearing human prostate cancer xenografts (subcutaneous DU 145 and PC-3M, orthotopic PC-3M).


RESULTS
One 4 mg/kg patupilone administration produced transient regression of DU 145 tumors, while two weekly administrations of 2.5 mg/kg produced stable disease followed by protracted regression, however with more pronounced body weight loss. Taxol (15 mg/kg every other day) weakly inhibited tumor growth, but with less body weight loss. Patupilone (5 mg/kg) produced protracted growth inhibition of subcutaneous PC-3M tumors, with transient body weight loss. In mice with orthotopic PC-3M tumors, 4 or 5 mg/kg/week patupilone impaired primary tumor growth, abrogated metastases and enhanced survival, with only transient body weight loss.


CONCLUSIONS
These data suggest that patupilone holds promise for prostate cancer treatment.
O'Reilly
Terence
T
Novartis Institutes for BioMedical Research, Oncology Research, Basel, Switzerland.
McSheehy
Paul Michael John
PM
Wenger
Fritz
F
Hattenberger
Marc
M
Muller
Melanie
M
Vaxelaire
Juliane
J
Altmann
Karl-Heinz
KH
Wartmann
Markus
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D034261:Epothilones / Q000494:pharmacology*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D034261:Epothilones; D017239:Paclitaxel; C093788:epothilone B