A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas

被引：59
作者：
Chu Q.S.C. [1 ]
Forouzesh B. [2 ]
Syed S. [2 ]
Mita M. [2 ]
Schwartz G. [3 ]
Copper J. [2 ]
Curtright J. [2 ]
Rowinsky E.K. [2 ]
机构：
[1] Cross Cancer Institute, Edmonton, Alta. T6G 1Z2
[2] Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX
[3] Brooke Army Medical Center, Fort Sam Houston, TX
来源：
Investigational New Drugs | 2007年 / 25卷 / 4期
关键词：
COL-3; Metalloproteinase inhibitor; Soft tissue sarcoma;
D O I：
10.1007/s10637-006-9031-6
中图分类号：
学科分类号：
摘要：
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. © 2007 Springer Science+Business Media, LLC.
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页码：359 / 367
页数：8
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