Kavanagh J J, Gershenson D M, Choi H, Lewis L, Patel K, Brown G L, Garcia A, Spriggs D R
The M.D. Anderson Cancer Center, University of Texas, Houston, Texas, USA.
Int J Gynecol Cancer. 2005 Jul-Aug;15(4):593-600. doi: 10.1111/j.1525-1438.2005.00114.x.
The purpose of this study was to determine the safety and efficacy of TLK286 (TELCYTA(TM)), a glutathione analog prodrug, in patients with platinum and paclitaxel refractory or resistant ovarian carcinoma. Thirty-six patients with measurable disease were enrolled. TLK286 was administered at 1000 mg/m2 intravenously every 3 weeks. The endpoints were objective response rate assessed by Response Evaluation Criteria in Solid Tumors (RECIST) and survival. Adverse events were graded using the National Cancer Institute Common Toxicity Criteria. Thirty-four platinum refractory or resistant patients (94%) were evaluable for objective tumor response. Five patients (15%) had objective tumor responses, including one durable complete response (CR) of greater than 3 years and continuing. The disease stabilization rate was 50%, including one CR (3%), four partial responses (12%), and 12 durable disease stabilizations (35%). Responses were accompanied by improvement in clinical symptoms and Eastern Cooperative Oncology Group Performance Status (ECOG PS) and decline in CA125 levels. Median survival was 423 days with survival of 60% at 1 year and 40% at 18 months. TLK286 was well tolerated in this population. TLK286 is an active agent in chemotherapy-resistant ovarian cancer. Further studies of TLK286 in platinum and paclitaxel refractory or resistant ovarian cancer are in progress.
本研究旨在确定谷胱甘肽类似物前体药物TLK286（TELCYTA™）在铂类和紫杉醇难治或耐药的卵巢癌患者中的安全性和疗效。招募了36例具有可测量病灶的患者。TLK286以1000mg/m²的剂量每3周静脉给药一次。终点指标为根据实体瘤疗效评价标准（RECIST）评估的客观缓解率和生存率。不良事件按照美国国立癌症研究所通用毒性标准进行分级。34例铂类难治或耐药患者（94%）可评估客观肿瘤反应。5例患者（15%）出现客观肿瘤反应，包括1例持续超过3年且仍在持续的持久完全缓解（CR）。疾病稳定率为50%，包括1例CR（3%）、4例部分缓解（12%）和12例持久疾病稳定（35%）。反应伴随着临床症状和东部肿瘤协作组体能状态（ECOG PS）的改善以及CA125水平的下降。中位生存期为423天，1年生存率为60%，18个月生存率为40%。TLK286在该人群中耐受性良好。TLK286是化疗耐药卵巢癌的一种有效药物。关于TLK286在铂类和紫杉醇难治或耐药卵巢癌中的进一步研究正在进行中。
