Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer.
OBJECTIVE
To evaluate the antitumor activity and safety of the epothilone B analog, ixabepilone, with or without estramustine phosphate (EMP), in chemotherapy-naive patients with progressive castrate metastatic prostate cancer.


METHODS
Patients were randomly assigned to receive ixabepilone (35 mg/m(2)) by intravenous infusion every 3 weeks with or without EMP 280 mg orally three times daily on days 1 to 5.


RESULTS
Between December 2001 and October 2003, 92 patients were enrolled and randomly assigned to treatment with ixabepilone alone (45 patients) or in combination with EMP (47 patients). Grades 3 and 4 toxicities experienced by more than 5% of patients included neutropenia (22%), fatigue (9%), and neuropathy (13%) on the ixabepilone arm, and neutropenia (29%), febrile neutropenia (9%), fatigue (9%), neuropathy (7%), and thrombosis (6%) on the ixabepilone + EMP arm. Post-treatment declines in prostate-specific antigen of > or = 50% were achieved in 21 of 44 patients (48%; 95% CI, 33% to 64%) on the ixabepilone arm, and 31 of 45 patients (69%; 95% CI, 55% to 82%) on the ixabepilone + EMP arm. In patients with measurable disease, partial responses were observed in eight of 25 patients (32%; 95% CI, 14% to 50%) on the ixabepilone arm, and 11 of 23 (48%; 95% CI, 27% to 68%) on the ixabepilone + EMP arm. Time to prostate-specific antigen progression was 4.4 months (95% CI, 3.1 to 6.9 months) on the ixabepilone-alone arm and 5.2 months (95% CI, 4.5 to 6.8 months) on the combination arm.


CONCLUSIONS
Ixabepilone, with or without estramustine phosphate, is well tolerated and has antitumor activity in patients with castrate metastatic prostate cancer.
Galsky
Matthew D
MD
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. galskym@mskcc.org
Small
Eric J
EJ
Oh
William K
WK
Chen
Isan
I
Smith
David C
DC
Colevas
A Dimitrios
AD
Martone
Lou
L
Curley
Tracy
T
Delacruz
Anthony
A
Scher
Howard I
HI
Kelly
W Kevin
WK
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002369:Castration; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects; D004961:Estramustine / Q000008:administration & dosage*; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013927:Thrombosis / Q000139:chemically induced
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D034261:Epothilones; D004961:Estramustine; C430592:ixabepilone