Summary
In a phase I study, ixabepilone, a novel non-taxane microtubule-stabilizing agent, demonstrated activity against both paclitaxel-sensitive and paclitaxel-refractory solid tumors. We conducted a phase II trial of this agent in patients with advanced germ cell tumors (GCT) who were resistant to conventional therapies.
Patients with cisplatin-refractory GCT were enrolled in this single-institution, phase II trial. Ixabepilone was administered at a dose of 40 mg/m2 intravenously over 3 hours every 21 days. Dose modifications were planned according to a nomogram for adverse events. Responses were assessed every 6 weeks using tumor markers and radiographic imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients who progressed (≥20% increase in tumor size or rising serum tumor markers) were taken off protocol.
Twenty-nine cycles of treatment were administered to 12 patients. The most common Grade 3/4 toxicities were leukopenia, lymphopenia, and neutropenia. One patient (8%) achieved a confirmed objective partial response but this patient had not received prior treatment with a taxane. Based on slow accrual and a lack of antitumor activity in patients previously treated with a taxane, the trial was closed after enrolling 12 patients.
For patients who had previously received taxane therapy, ixabepilone was not efficacious in the treatment of cisplatin-refractory GCT.
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Acknowledgments
This clinical trial was supported by NIH Grants CM-57732 and CA-05826 and by the Craig D. Tifford Foundation. The authors thank Carol Pearce, Writer/Editor, Memorial Sloan-Kettering Cancer Center Department of Medicine Editorial Unit, for her critical review of this manuscript.
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Feldman, D.R., Kondagunta, G.V., Ginsberg, M.S. et al. Phase II Trial of ixabepilone in patients with cisplatin-refractory germ cell tumors. Invest New Drugs 25, 487–490 (2007). https://doi.org/10.1007/s10637-007-9059-2
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DOI: https://doi.org/10.1007/s10637-007-9059-2