Dataset Information

Phase II trial of weekly ixabepilone in men with metastatic castrate-resistant prostate cancer (E3803): a trial of the Eastern Cooperative Oncology Group.

ABSTRACT:

Unlabelled

Ixabepilone is an epothilone B analogue with activity in a variety of solid malignancies, including prostate cancer. The main dose-limiting toxicity of ixabepilone is myelosuppression when administered by using an every 3-week schedule. Here we evaluate the activity of a weekly ixabepilone in men with metastatic castrate-resistant prostate cancer to minimize hematologic toxicity.

Purpose

BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistant cancer cell lines. Here we report the activity and toxicity of ixabepilone, administered by using a weekly schedule, in men with metastatic castrate-resistant prostate cancer (CRPC).

Experimental design

Patients with metastatic CRPC received ixabepilone at 20 mg/m(2) intravenous weekly x 3, in 4-week cycles. This noncomparative study stratified patients to either a chemotherapy naive (CN), prior taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The primary endpoint was prostate-specific antigen response by using PCWG (Prostate Cancer Working Group) 1 criteria. Secondary endpoints included radiographic response when using RECIST (Response Evaluation Criteria In Solid Tumors).

Results

In total, 124 patients were enrolled, of whom, 109 were eligible (35 CN, 42 Tax, and 32 TCx) for the primary response determination in this study. Prostate-specific antigen responses were seen in 12 (34.3%) of 35, 12 (28.6%) of 42, and 7 (21.9%) of 32 patients with the partial objective response in 5 (22.7%) of 22, 2 (8.0%) of 25, and 0 (0.0%) of 24 patients for the CN, Tax, and TCx arms, respectively. Significant (grade 3/4) neutropenia was seen in 6 (15.4%), 7 (14.6%), and 9 (25.0%); and grade 3/4 sensory neuropathy was seen in 8 (20.5%), 12 (25.0%), and 12 (33.3%) for CN, Tax, and TCx, respectively. Grade 3/4 thrombocytopenia was infrequent and seen in only one patient on the CN and the TCx arm.

Conclusion

Ixabepilone was found to have an acceptable toxicity profile when administered by using a weekly schedule with less myelosuppression compared with prior studies when using the every 3-week schedule. Single-agent activity was observed and met prespecified activity levels for the Tax treated arm.

SUBMITTER: Liu G

PROVIDER: S-EPMC3535436 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Phase II trial of weekly ixabepilone in men with metastatic castrate-resistant prostate cancer (E3803): a trial of the Eastern Cooperative Oncology Group.

Liu Glenn G Chen Yu-Hui YH Dipaola Robert R Carducci Michael M Wilding George G

Clinical genitourinary cancer 20120303 2

<h4>Unlabelled</h4>Ixabepilone is an epothilone B analogue with activity in a variety of solid malignancies, including prostate cancer. The main dose-limiting toxicity of ixabepilone is myelosuppression when administered by using an every 3-week schedule. Here we evaluate the activity of a weekly ixabepilone in men with metastatic castrate-resistant prostate cancer to minimize hematologic toxicity.<h4>Purpose</h4>BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resist ...[more]

PMID: 22386239

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Dataset Information

Phase II trial of weekly ixabepilone in men with metastatic castrate-resistant prostate cancer (E3803): a trial of the Eastern Cooperative Oncology Group.

Unlabelled

Purpose

Experimental design

Results

Conclusion

Publications

Phase II trial of weekly ixabepilone in men with metastatic castrate-resistant prostate cancer (E3803): a trial of the Eastern Cooperative Oncology Group.

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