A multicenter phase II study of the cryptophycin analog LY355703 in patients with platinum-resistant ovarian cancer
A multicenter phase II study of the cryptophycin analog LY355703 in patients with platinum-resistant ovarian cancer
复制标题
DOI：
10.1111/j.1525-1438.2006.00276.x
复制
发表时间：
2006-01-01
影响因子：
4.8
通讯作者：
Scambia, G
中科院分区：
文献类型：
--
作者：
D'Agostino, G;Del Campo, J;Scambia, G
LY355703 是一种结构上与从蓝绿藻中分离出来的隐藻素家族相关的合成产品，它在有丝分裂过程中对微管产生有效的不稳定作用。本研究旨在确定 LY355703 在铂类耐药晚期卵巢癌患者中的活性并表征其毒性特征。二十六名患者参加了这项研究。耐药性疾病被定义为从初次治疗或再次挑战起的无铂治疗间隔<6个月。 LY355703（1.5 mg/m(2)）在第1天和第8天静脉注射，每3周一次，输注时间超过2小时。 24 名可评估疗效的患者中，有 3 名部分缓解 (12.5%) 和 7 名疾病稳定 (29.2%)，总体临床获益率为 41.7%。 14 名患者（58.3%）在治疗期间病情出现进展。在可评估毒性的 25 名患者中，有两次 3 级贫血发作（8%）；一、3级血小板减少症（4%）；一、肌酐4级升高（4%）；一是报告了 3 级高胆红素血症（4%）。 LY355703 对铂类耐药的晚期卵巢癌患者具有适度的活性。然而，在这个预后不良的研究人群中，在没有严重不良事件的情况下，疾病稳定率相当高，这表明这种新型隐藻素可能值得在这种情况下进行进一步研究。
LY355703 is a synthetic product structurally related to the cryptophycin family isolated from the blue-green algae, which exerts a potent destabilization of microtubules during mitosis. This study was performed to determine the activity of LY355703 in patients with platinum-resistant advanced ovarian cancer and to characterize its toxicity profile. Twenty-six patients were enrolled in this study. Resistant disease was defined as a platinum-free interval of < 6 months from primary treatment or rechallenge. LY355703 (1.5 mg/m(2)) was administered intravenously on days 1 and 8, every 3 weeks, infused over 2 h. From 24 patients evaluable for response, three partial responses (12.5%) and seven disease stabilizations were registered (29.2%), for an overall clinical benefit of 41.7%. Fourteen patients (58.3%) experienced a progression of the disease during treatment. Among the 25 patients evaluable for toxicity, two episodes of grade 3 anemia (8%); one, grade 3 thrombocytopenia (4%); one, grade 4 elevation of creatinine (4%); and one, grade 3 hyperbilirubinemia (4%) were reported. LY355703 has a modest activity in patients with platinum-resistant advanced ovarian cancer. Nevertheless, the considerable rate of disease stabilization in the absence of serious adverse events in this poor-prognosis study population suggests that this novel cryptophycin may deserve further investigation in this setting.