A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas.
A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas.
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DOI：
10.1007/s10637-006-9031-6
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Rowinsky, Eric K
中科院分区：
文献类型：
--
作者：
Chu, Quincy S C;Forouzesh, Bahram;Rowinsky, Eric K
这项II期研究评价了四环素类似物COL-3的抗肿瘤活性，COL-3是一种金属蛋白酶（MMP），特别是MMP-2和MMP-9的强效抑制剂，以50 mg/m2每日剂量连续口服给药，治疗晚期和/或转移性软组织肉瘤（STS）患者。主要终点是客观肿瘤消退率和治疗前8周内未发生疾病进展的患者比例。其他研究目的包括评估COL-3的药理学、疾病进展时间（TTP）和总生存期。采用Simon两阶段设计和多项终止规则，在研究的第一阶段入组了15例患者。尽管COL-3通常耐受良好，但在治疗的前8周内没有客观反应，5名（33%）患者经历了疾病进展，这超过了关于在STS中进一步评价COL-3的先验标准。TTP和生存期的中位数分别为109天和279天。基于这些结果，不需要在STS患者中进一步研究COL-3的给药方案。
This phase II study evaluated the antitumor activity of the tetracycline analog COL-3, a potent inhibitor of metalloproteinases (MMPs), particularly MMP-2 and MMP-9, on a continuous oral schedule at a dose of 50 mg/m2 daily in patients with advanced and/or metastatic soft tissue sarcoma (STS). The principal endpoints were the rate of objective tumor regression and the proportion of patients who did not experience disease progression during the first 8 weeks of treatment. Other study objectives included an assessment of pharmacology of COL-3, time to progression (TTP), and overall survival. A Simon two-stage design with multinomial stopping rule was employed, with 15 patients enrolled during the first stage of the study. Although COL-3 was generally well-tolerated, there were no objective responses and 5(33%) patients experienced disease progression during the first 8 weeks of treatment, which exceeded the criteria established a priori with regard to pursuing further evaluations of COL-3 in STS. The median values for TTP and survival were 109 and 279 days, respectively. Based on these results, further studies of COL-3 on this administration schedule in patients with STS are not warranted.