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Narra K , Mullins SR , Lee HO , Strzemkowski-Brun B , Magalong K , Christiansen VJ , McKee PA , Egleston B , Cohen SJ , Weiner LM , Meropol NJ , Cheng JD
Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer
Cancer Biol Ther. 2007 Nov;6(11) :1691-9
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Abstract
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 microg 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 II 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.
Notes
Narra, Kalyani Mullins, Stefanie R Lee, Hyung-Ok Strzemkowski-Brun, Brenda Magalong, Kimberly Christiansen, Victoria J McKee, Patrick A Egleston, Brian Cohen, Steven J Weiner, Louis M Meropol, Neal J Cheng, Jonathan D eng CA006927/CA/NCI NIH HHS/ CA090468/CA/NCI NIH HHS/ CA122301/CA/NCI NIH HHS/ HL072995-01/HL/NHLBI NIH HHS/ Clinical Trial, Phase II Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Cancer Biol Ther. 2007 Nov;6(11):1691-9. doi: 10.4161/cbt.6.11.4874. Epub 2007 Aug 14.