title: Phase II trial of ixabepilone in patients with cisplatin-refractory germ cell tumors.
abstract: 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 (>or=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.
authors.affiliation: Genitourinary service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
authors.forename: G Varuni
authors.initials: GV
authors.lastname: Kondagunta
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Ginsberg
authors.forename: Nicole
authors.initials: N
authors.lastname: Ishill
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: John
authors.initials: J
authors.lastname: Cestaro
authors.forename: Eugenie
authors.initials: E
authors.lastname: Obbens
authors.forename: Joel
authors.initials: J
authors.lastname: Sheinfeld
authors.forename: George J
authors.initials: GJ
authors.lastname: Bosl
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone; D002945:Cisplatin