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 Journal Article

  

Authors:	Galsky, M. D.; Small, E. J.; Oh, W. K.; Chen, I.; Smith, D. C.; Colevas, A. D.; Martone, L.; Curley, T.; Delacruz, A.; Scher, H. I.; Kelly, W. K.
Article Title:	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
Abstract:	Purpose: 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. Patients and Methods: Patients were randomly assigned to receive ixabepilone (35 mg/m2) 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 ≥ 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. Conclusion: Ixabepilone, with or without estramustine phosphate, is well tolerated and has antitumor activity in patients with castrate metastatic prostate cancer.
Keywords:	adult; controlled study; treatment response; aged; aged, 80 and over; middle aged; major clinical study; clinical trial; disease course; drug tolerability; fatigue; neutropenia; paresthesia; diarrhea; drug dose reduction; drug safety; drug withdrawal; side effect; antineoplastic agents; bone metastasis; follow up; antineoplastic agent; prostate specific antigen; demography; metastasis; computer assisted tomography; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; nausea; neuropathy; randomized controlled trial; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; peripheral neuropathy; alkylating agent; dexamethasone; deep vein thrombosis; antineoplastic activity; drug hypersensitivity; febrile neutropenia; prostate cancer; lung embolism; prostatic neoplasms; heart infarction; multicenter study; thromboembolism; chemically induced disorder; thrombosis; prophylaxis; prostate tumor; antineoplastic agents, alkylating; warfarin; neoplasm metastasis; castration; antineoplastic agents, hormonal; antineoplastic hormone agonists and antagonists; peripheral nervous system diseases; ixabepilone; epothilones; epothilone b; epothilone derivative; diphenhydramine; dysesthesia; castrated male; ranitidine; estramustine; estramustine phosphate
Journal Title:	Journal of Clinical Oncology
Volume:	23
Issue:	7
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2005-03-01
Start Page:	1439
End Page:	1446
Language:	English
DOI:	10.1200/jco.2005.09.042
PUBMED:	15735119
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-20144377696&partnerID=40&md5=b5034d953c8830f7d3dc752a1574780a
Notes:	--- - "Cited By (since 1996): 142" - "Export Date: 24 October 2012" - "CODEN: JCOND" - "Source: Scopus"

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