A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer.
A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer.
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DOI：
10.1097/jto.0b013e31822e2941
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
California Consortium
中科院分区：
文献类型：
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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
AT-101是抗凋亡Bcl蛋白（Bcl-2、Bcl-XL、Bcl-W和Mcl-1）的口服抑制剂，也是促凋亡蛋白noxa和puma的诱导剂。我们研究了AT-101在复发性化学敏感广泛期小细胞肺癌（ES-SCLC）患者中的疗效。复发性“敏感”SCLC患者（定义为一线铂类化疗期间无进展且完成后< 2个月无疾病复发）符合条件。AT-101每天口服20 mg，每个周期28天中的21天，最多6个周期。主要终点为客观缓解率。在计划的中期评价时，入组第一阶段的14例可评价患者均未对治疗产生任何反应，研究永久关闭以进行进一步招募。三名患者（21%）在两个周期的治疗后病情稳定。3级毒性包括厌食、疲劳和恶心/呕吐。AT-101在复发性化学敏感性SCLC患者中无活性。支持N 01-CM 62205。
AT-101 is an oral inhibitor of the anti-apoptotic Bcl proteins (Bcl-2, Bcl-XL, Bcl-W, and Mcl-1) and an inducer of the pro-apoptotic proteins noxa and puma. We studied the efficacy of AT-101 in patients with recurrent chemosensitive extensive stage – small cell lung cancer (ES-SCLC). Patients with recurrent “sensitive” SCLC (defined as no progression during and no disease recurrence < 2 months after completion of first-line platinum-based chemotherapy) were eligible. AT-101 was administered 20 mg orally daily for 21 out of 28 days each cycle for up to 6 cycles. The primary endpoint was the objective response rate. At the time of planned interim evaluation, none of the 14 evaluable patients enrolled in the first stage had any response to therapy and the study was closed permanently for further accrual. Three patients (21 %) achieved stable disease after two cycles of therapy. Grade 3 toxicities included anorexia, fatigue, and nausea/vomiting. AT-101 is not active in patients with recurrent chemosensitive SCLC. Supported by N01-CM62205.