Feldman Darren R, Kondagunta G Varuni, Ginsberg Michelle S, Ishill Nicole, Patil Sujata, Cestaro John, Obbens Eugenie, Sheinfeld Joel, Bosl George J, Motzer Robert J
Genitourinary service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Invest New Drugs. 2007 Oct;25(5):487-90. doi: 10.1007/s10637-007-9059-2. Epub 2007 May 23.
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.
在一项I期研究中，新型非紫杉烷类微管稳定剂伊沙匹隆对紫杉醇敏感和紫杉醇难治性实体瘤均显示出活性。我们对常规治疗耐药的晚期生殖细胞肿瘤（GCT）患者进行了该药物的II期试验。顺铂难治性GCT患者被纳入这项单机构II期试验。伊沙匹隆以40mg/m²的剂量每21天静脉输注3小时给药。根据不良事件列线图计划进行剂量调整。根据实体瘤疗效评价标准（RECIST），每6周使用肿瘤标志物和影像学检查评估疗效。病情进展（肿瘤大小增加≥20%或血清肿瘤标志物升高）的患者退出试验。对12例患者进行了29个周期的治疗。最常见的3/4级毒性反应为白细胞减少、淋巴细胞减少和中性粒细胞减少。1例患者（8%）获得了确认的客观部分缓解，但该患者之前未接受过紫杉烷类治疗。基于入组缓慢以及先前接受过紫杉烷类治疗的患者缺乏抗肿瘤活性，在入组12例患者后试验结束。对于先前接受过紫杉烷类治疗的患者，伊沙匹隆治疗顺铂难治性GCT无效。
