A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer
A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer
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DOI：
10.1016/j.ygyno.2008.06.028
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发表时间：
2008-10-01
影响因子：
4.7
通讯作者：
Gold, Michael A.
中科院分区：
文献类型：
--
作者：
Ghamande, Sharad A.;Silverman, Michael H.;Gold, Michael A.
目标. Angstrom 6是一种新的肽，其干扰单链尿激酶纤溶酶原激活剂活性，并显示出抗血管生成、抗迁移和抗侵入性质。我们评估了皮下注射Angstrom 6治疗卵巢上皮性癌的临床疗效和安全性。患有上皮性卵巢癌、输卵管癌或原发性腹膜癌的妇女，在一线化疗后临床缓解，CA 125值连续2次升高高于正常值，但在体格检查或影像学研究中无疾病，被随机分配接受每日皮下注射安慰剂、低剂量Angstrom 6（150 mg）、或高剂量Angstrom 6（300 mg），直至疾病进展或研究参与结束。主要终点是疾病临床进展时间和angstrom 6的安全性。次要终点是血清CA 125和尿激酶系统生物标志物的变化。24名女性的数据可用（安慰剂组，n= 12;低剂量组，n=8;高剂量组n=4）。Angstrom 6治疗与临床进展时间的统计学显著延迟相关（对数秩p值0.01），接受Angstrom 6治疗的女性的中位时间为100天（95%CI：64.168），而接受安慰剂治疗的女性为49天（95%CI：29.67）。这些治疗似乎耐受良好。治疗与CA 125应答无关（p=0.44）。与安慰剂组相比，Angstrom 6组的治疗期间血浆尿激酶纤溶酶原激活物受体值在统计学上显著降低（p=0.02）。埃6治疗增加了临床疾病进展的时间，并且似乎在该患者群体中耐受良好。(C)2008年爱思唯尔公司All rights reserved.
Objectives. angstrom 6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered angstrom 6 in women with epithelial ovarian cancer.Methods. Women with epithelial ovarian, fallopian tube, or primary peritoneal cancer in clinical remission after first-line chemotherapy with 2 consecutive increases of CA125 values above normal but with no disease on physical examination or imaging studies were randomly assigned to receive daily subcutaneous injections of placebo, low-dose angstrom 6 (150 mg), or high-dose angstrom 6 (300 mg) until disease progression or end of study participation. Primary endpoints were time to clinical progression of disease and safety of angstrom 6. Secondary endpoints were changes in serum CA 125 and biomarkers of the urokinase system.Results. Data are available for 24 women (placebo, n= 12: low-dose, n=8; high-dose n=4). angstrom 6 therapy was associated with a statistically significant delay in time to clinical progression (log-rank p-value 0.01) with a median of 100 days (95% CI: 64 168) for women who received angstrom 6 compared with 49 days (95% CI: 29,67) for women who received placebo. The treatments appeared to be well tolerated. Treatment was not associated with CA125 response (p=0.44). On-treatment values for plasma urokinase plasminogen activator receptor were statistically significantly lower in the angstrom 6 groups compared with placebo (p=0.02).Conclusions. angstrom 6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population. (C) 2008 Elsevier Inc. All rights reserved.