A phase II study of the orally administered negative enantiomer of gossypol (AT-101), a BH3 mimetic, in patients with advanced adrenal cortical carcinoma.
A phase II study of the orally administered negative enantiomer of gossypol (AT-101), a BH3 mimetic, in patients with advanced adrenal cortical carcinoma.
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DOI：
10.1007/s10637-019-00797-1
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发表时间：
2019-08
影响因子：
3.4
通讯作者：
Adjei AA
中科院分区：
文献类型：
--
作者：
Xie H;Yin J;Shah MH;Menefee ME;Bible KC;Reidy-Lagunes D;Kane MA;Quinn DI;Gandara DR;Erlichman C;Adjei AA
肾上腺皮质癌（ACC）是一种罕见的癌症，治疗方法有限，如果转移，预后不良。AT-101是B细胞淋巴瘤2家族增殖相关蛋白的抑制剂，其外消旋形式棉酚在ACC中显示出初步的临床活性。因此，我们评估了AT-101在晚期ACC患者中的疗效。（20 mg/天口服，28天周期中的21天），直至疾病进展和/或出现抑制性毒性。主要终点是客观缓解率，其中实体瘤缓解评价标准（RECIST）部分缓解率为25%被视为有希望，10%被视为无希望，I类错误率为10%，把握度为90%。在2阶段设计中，前21例可评估受试者需要2例应答，以保证44例患者的完全入组。次要终点包括安全性、无进展生存期和总生存期。该研究在2009年至2011年期间招募了29例患者;中位周期数为2。7%的人经历了4级毒性，包括心肌肌钙蛋白升高和低钾血症。前21例患者均未达到RECIST部分缓解;因此，认为研究治疗无效，试验永久关闭。AT-101在本研究中对晚期ACC患者没有有意义的临床活性，但证明了在这种罕见癌症中进行前瞻性治疗临床试验的可行性。
Adrenal cortical carcinoma (ACC) is a rare cancer with treatment options of limited efficacy, and poor prognosis if metastatic. AT-101 is a more potent inhibitor of B cell lymphoma 2 family apoptosis-related proteins than its racemic form, gossypol, which showed preliminary clinical activity in ACC. We thus evaluated the efficacy of AT-101 in patients with advanced ACC. Patients with histologically confirmed metastatic, recurrent, or primarily unresectable ACC were treated with AT-101 (20 mg/day orally, 21 days out of 28-day cycles) until disease progression and/or prohibitive toxicity. The primary endpoint was objective response rate, wherein a Response Evaluation Criteria In Solid Tumors (RECIST) partial response rate of 25% would be considered promising and 10% not, with a Type I error of 10% and 90% power. In a 2-stage design, 2 responses were required of the first 21 assessable subjects to warrant complete accrual of 44 patients. Secondary endpoints included safety, progression-free survival and overall survival. This study accrued 29 patients between 2009 and 2011; median number of cycles was 2. Seven percent experienced grade 4 toxicity including cardiac troponin elevations and hypokalemia. None of the first 21 patients attained RECIST partial response; accordingly, study therapy was deemed ineffective and the trial was permanently closed. AT-101 had no meaningful clinical activity in this study in patients with advanced ACC, but demonstrated feasibility of prospective therapeutic clinical trials in this rare cancer.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1097/jto.0b013e31822e2941
发表时间：
2011-10
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Baggstrom MQ;Qi Y;Koczywas M;Argiris A;Johnson EA;Millward MJ;Murphy SC;Erlichman C;Rudin CM;Govindan R;Mayo Phase 2 Consortium;California Consortium
通讯作者：
California Consortium
影响因子：
1.9
作者：
FLEMING, TR
通讯作者：
FLEMING, TR
影响因子：
20.4
作者：
Ready, Neal;Karaseva, Nina A.;Leopold, Lance
通讯作者：
Leopold, Lance
影响因子：
3.9
作者：
Sperone, Paola;Ferrero, Anna;Berruti, Alfredo
通讯作者：
Berruti, Alfredo