Phase II trial of single agent Val-boroPro (Talabostat) inhibiting fibroblast activation protein in patients with metastatic colorectal cancer
Phase II trial of single agent Val-boroPro (Talabostat) inhibiting fibroblast activation protein in patients with metastatic colorectal cancer
复制标题
DOI：
10.4161/cbt.6.11.4874
复制
发表时间：
2007-11-01
影响因子：
3.6
通讯作者：
Cheng, Jonathan D.
中科院分区：
文献类型：
--
作者：
Narra, Kalyani;Mullins, Stefanie R.;Cheng, Jonathan D.
目的：成纤维细胞活化蛋白（FAP）是一种肿瘤成纤维细胞蛋白酶，已被证明可促进结直肠癌的生长。使用Val-boroPro（Talabostat）测试FAP抑制的临床影响，该药物是转移性结直肠癌患者的II期研究中FAP酶活性的第一种临床抑制剂。连续出价。合格性包括可测量的疾病、0至2的体能状态和足够的器官功能。实验室相关性评价的药效学作用Val-boroPro对FAP酶功能在外周blood.Results：28例患者（中位年龄62; 12名男性，16名女性）参加了这项研究。没有客观的答复。28例患者中有6例（21%）病情稳定，中位数为25周（范围11-38周）。实验室分析表明显着的，虽然不完全抑制FAP酶活性在外周blood.Conclusion：这11期临床试验的Val-boroPro表现出最小的临床活性与以前治疗的转移性结直肠癌患者。然而，它提供了初步的概念验证，即FAP活性的生理抑制可以在结直肠癌患者中完成，并为未来针对肿瘤间质的研究奠定了基础。
Purpose: Fibroblast Activation Protein (FAP) is a tumor fibroblast protease that has been shown to potentiate colorectal cancer growth. The clinical impact of FAP inhibition was tested using Val-boroPro (Talabostat), the first clinical inhibitor of FAP enzymatic activity in a phase II study of patients with metastatic colorectal cancer.Methods: Patients with metastatic colorectal cancer who had previously received systemic chemotherapies were treated with single agent Val-boroPro 200 mu g p.o. BID continuously. Eligibility included measurable disease, performance status of 0 to 2, and adequate organ function. Laboratory correlates evaluated the pharmacodynamic effects of Val-boroPro on FAP enzymatic function in the peripheral blood.Results: Twenty-eight patients (median age 62; 12 males, 16 females) were enrolled in this study. There were no objective responses. Six of 28 (21 %) patients had stable disease for a median of 25 weeks (range 11-38 weeks). Laboratory analysis demonstrated significant, although incomplete inhibition of FAP enzymatic activity in the peripheral blood.Conclusion: This phase 11 trial of Val-boroPro demonstrated minimal clinical activity in patients with previously treated metastatic colorectal cancer. However it provides the initial proof-of-concept that physiologic inhibition of FAP activity can be accomplished in patients with colorectal cancer, and lays the groundwork for future studies targeting the tumor stroma.