Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: A gynecologic oncology group study
Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: A gynecologic oncology group study
复制标题
DOI：
10.1016/j.ygyno.2014.01.015
复制
发表时间：
2014-03-01
影响因子：
4.7
通讯作者：
Leslie, Kimberly K.
中科院分区：
文献类型：
--
作者：
Fleming, Gini F.;Filiaci, Virginia L.;Leslie, Kimberly K.
目标。目的：确定替西罗莫司联合或不联合激素治疗晚期或复发子宫内膜癌的疗效、毒性和无进展生存期。临床前证据表明，阻断PI3K/AKT/mTOR通路可能克服对激素治疗的抵抗。在复发或转移性子宫内膜癌患者中，我们进行了一项随机的II期试验，每周静脉注射替西罗莫司25 mg，与每周替西罗莫司联合甲地孕酮80 mg，每日2次，共3周，同时他莫昔芬20 mg，每日2次，共3周。71名符合条件的患者接受了至少一剂治疗，其中21名患者在联合组接受治疗，该组因静脉血栓形成过多而提前闭合，其中5例发生深静脉血栓形成(DVT)，2例发生肺血栓。在那只手臂上观察到了三种反应(14%)。共有50例符合条件的患者在单一药物ARM上接受治疗，发生3次DVT，11例有效(22%)。接受过化疗的患者的有效率(7/29；24%)与未接受过化疗的患者(4/21；19%)相似。4例透明细胞癌患者中有2例有效。在替西罗莫司治疗中加入甲地孕酮和他莫昔芬的联合治疗并没有增强活性，而且联合治疗会导致过量的静脉血栓形成。在接受过辅助化疗的患者中，泰西罗莫司的活性得以保留。(C)2014 Elsevier Inc.保留所有权利。
Objectives. To determine the response, toxicities, and progression free survival of a regimen of temsirolimus with or without hormonal therapy in the treatment of advanced, or recurrent endometrial carcinoma.Background. Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy.Methods. We performed a randomized phase II trial of intravenous temsirolimus 25 mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks alternating with tamoxifen 20 mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma.Results. There were 71 eligible patients who received at least one dose of therapy with 21 of these treated on the combination arm which was closed early because of an excess of venous thrombosis, with 5 episodes of deep venous thrombosis (DVT) and 2 pulmonary emboli. There were three responses observed in that arm (14%). A total of 50 eligible patients were treated on the single agent arm with 3 episodes of DVT and 11 responses (22%). Response rates were similar in patients with prior chemotherapy (7 of 29; 24%) and those with no prior chemotherapy (4 of 21; 19%). Two of four patients with clear cell carcinoma responded.Conclusions. Adding the combination of megestrol acetate and tamoxifen to temsirolimus therapy did not enhance activity and the combination was associated with an excess of venous thrombosis. Temsirolimus activity was preserved in patients with prior adjuvant chemotherapy. (C) 2014 Elsevier Inc. All rights reserved.