Phase II Trial of ixabepilone in patients with cisplatin-refractory germ cell tumors
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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.
Keywords
Ixabepilone Germ cell tumors Clinical trial BMS-247550Notes
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.
References
- 1.Kondagunta GV, Motzer RJ (2006) Chemotherapy for advanced germ cell tumors. J Clin Oncol 24:5493–5502PubMedCrossRefGoogle Scholar
- 2.Beyer J, Kramar A, Mandanas R et al (1996) High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables. J Clin Oncol 14:2638–2645PubMedGoogle Scholar
- 3.Bollag DM, McQueney PA, Zhu J et al (1995) Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 55:2325–2333PubMedGoogle Scholar
- 4.Lee FY, Borzilleri R, Fairchild CR et al (2001) BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin Cancer Res 7:1429–1437PubMedGoogle Scholar
- 5.Chou TC, Zhang XG, Harris CR et al (1998) Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel. Proc Natl Acad Sci U S A 95:15798–15802PubMedCrossRefGoogle Scholar
- 6.Mani S, McDaid H, Hamilton A et al (2004) Phase I clinical and pharmacokinetic study of BMS-247550, a novel derivative of epothilone B, in solid tumors. Clin Cancer Res 10:1289–1298PubMedCrossRefGoogle Scholar
- 7.Simon R (1989) Optimal two-stage designs for phase II clinical trials. Contr Clin Trials 10:1–10CrossRefGoogle Scholar