UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: A study of the Princess Margaret Hospital Phase II consortium
UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: A study of the Princess Margaret Hospital Phase II consortium
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DOI：
10.1016/j.ygyno.2007.02.018
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发表时间：
2007-08-01
影响因子：
4.7
通讯作者：
Oza, Amit M.
中科院分区：
文献类型：
--
作者：
Welch, Stephen;Hirte, Hal W.;Oza, Amit M.
背景和目标。UCN-01是一种星形孢菌素类似物，显示通过抑制细胞周期蛋白依赖性激酶消除G2检查点。临床前证据表明UCN-01和细胞毒性化疗之间存在协同作用。拓扑替康是卵巢癌的活性药物。本II期研究旨在探讨拓扑替康和UCN-01治疗晚期卵巢癌患者的安全性和有效性。一项两阶段II期试验设计用于既往接受铂类和紫杉醇治疗但疾病进展的晚期卵巢癌患者。晚期卵巢癌患者接受拓扑替康治疗，1 mg/m2 IV，第1 - 5天，UCN-01 70 mg/m2在第1个周期的第1天，35 mg/m2在所有后续周期的第1天。以3周为一周期重复治疗。本研究的主要目的是客观缓解率，次要目的包括疾病稳定率、缓解持续时间、无进展生存期和总生存期以及毒性。同时尽可能收集肿瘤活检标本进行分子相关性研究。29例患者可评价毒性和疗效。3例患者（10%）获得部分缓解。中位至进展时间为3.3个月（95% CI 1.5-NA），中位总生存期为9.7个月（95% CI：7.5-15.3）。最常见的3-4级毒性反应为中性粒细胞减少（79%）、贫血（41%）、血小板减少（14%）、高血糖（10%）和疼痛（10%）。UCN-01和托泊替康的组合通常耐受良好，然而，认为该组合对晚期卵巢癌不具有显著的抗肿瘤活性。(C)2007年爱思唯尔公司All rights reserved.
Background and objective. UCN-01 is a staurosporine analogue shown to abrogate the G2 checkpoint through inhibition of cyclin-dependent kinases. Preclinical evidence suggests synergy between UCN-01 and cytotoxic chemotherapy. Topotecan is an active agent in ovarian cancer. This phase II study was conducted to investigate the safety and efficacy of topotecan and UCN-01 in patients with advanced ovarian cancer.Methods. A two-stage phase II trial was designed for patients with advanced ovarian cancer with progressive disease despite prior treatment with platinum and paclitaxel. Patients with advanced ovarian cancer were treated with topotecan, 1 mg/m(2) IV, days 1 to 5, and UCN-01 70 mg/m(2) on day 1 of the first cycle, and 35 mg/m2 on day 1 of all subsequent cycles. Treatment was repeated on a 3-week cycle. The primary objective of this study was objective response rate while secondary objectives included rates of stable disease, duration of response, progression-free and overall survival, as well as toxicity. Tumor biopsy specimens were also collected where possible for molecular correlative studies.Results. Twenty-nine patients are evaluable for toxicity and efficacy. Three patients (10%) achieved a partial response. The median time to progression was 3.3 months (95% CI 1.5-NA), and the median overall survival was 9.7 months (95% CI: 7.5-15.3). The most common grade 3-4 toxicities were neutropenia (79%), anemia (41%), thrombocytopenia (14%), hyperglycemia (10%), and pain (10%).Conclusion. The combination of UCN-01 and topotecan is generally well tolerated, however, this combination is not considered to have significant antitumor activity against advanced ovarian cancer. (C) 2007 Elsevier Inc. All rights reserved.