Efficacy and safety of AEZS-108 (LHRH agonist linked to doxorubicin) in women with advanced or recurrent endometrial cancer expressing LHRH receptors: a multicenter phase 2 trial (AGO-GYN5).
Efficacy and safety of AEZS-108 (LHRH agonist linked to doxorubicin) in women with advanced or recurrent endometrial cancer expressing LHRH receptors: a multicenter phase 2 trial (AGO-GYN5).
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DOI：
10.1097/igc.0000000000000044
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发表时间：
2014-02
期刊：
影响因子：
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通讯作者：
Sehouli J
中科院分区：
文献类型：
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作者：
Emons G;Gorchev G;Harter P;Wimberger P;Stähle A;Hanker L;Hilpert F;Beckmann MW;Dall P;Gründker C;Sindermann H;Sehouli J
晚期或复发性子宫内膜癌（EC）不再适合手术或放疗是一种危及生命的疾病，治疗选择有限。80%的内皮细胞表达促黄体生成激素释放激素（LHRH）受体，AEZS-108（醋酸佐他瑞林多柔比星）可以靶向该受体。这项2期试验的目的是评估AEZS-108在这组患者中的疗效和安全性。患者患有FIGO（Fédération Internationale de Gynécologie et d 'Obstétrique）III或IV级或复发性EC、LHRH受体阳性肿瘤状态，并且至少有1处可测量病灶（实体瘤疗效评价标准）。不允许既往接受蒽环类药物治疗。患者在21天周期的第1天接受AEZS-108 2小时输注。治疗最多持续6至8个周期。主要终点是根据实体瘤疗效评价标准确定的缓解率。从2008年4月至2009年11月，德国（AGO）的8家研究中心和保加利亚的3家研究中心的44例患者入组研究。其中43例患者符合条件。2例（5%）患者完全缓解，8例（18%）患者部分缓解。44%的患者病情稳定至少6周。中位进展时间为7个月，中位总生存期为15个月。最常报告的3级或4级不良反应是中性粒细胞减少症（12%）和白细胞减少症（9%）。AEZS-108是一种与阿霉素偶联的LHRH激动剂，在晚期或复发性LHRH受体阳性EC的女性中具有显著的活性和低毒性，支持受体介导的靶向化疗的原理。
Advanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone–releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients. Patients had FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) III or IV or recurrent EC, LHRH receptor–positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors. From April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%). AEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor–positive EC, supporting the principle of receptor-mediated targeted chemotherapy.