Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor

<p> <p id="x-x-p-1"> <em> Purpose: </em> The purpose of this study was to evaluate the feasibility of incorporating a novel wound angiogenesis assay into a Phase I study of BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor, and to determine whether the wound angiogenesis assay was able to detect the inhibition of angiogenesis in patients treated with BMS-275291. <p id="x-x-p-2"> <em> Experimental Design: </em> Before treatment began, a 4-mm skin biopsy was performed. The wound was imaged for 14 days. Treatment was started on day 0, and a separate 4-mm biopsy was performed 14 days later. The second wound was also imaged for 14 days. Wound angiogenesis was scored by two independent observers who were blinded to treatment status. <p id="x-x-p-3"> <em> Results: </em> The median times in days (95% confidence interval) to reach the target average vascular score (AVS) of 1.5 and 2.0 based on the data of Observer 1 were 3.7 (2.2&ndash;6.9) and 8.0 (5.0&ndash;10.0) pretreatment whereas on-treatment the values were 4.9 (3.7&ndash;8.0) and 9.3 (7.0&ndash;11.5), respectively. The delay in the median time to reach an AVS of 1.5 was 1.2 days or a 32% reduction when comparing pretreatment with on-treatment ( <em> P </em> = 0.06). For the target AVS of 2.0 the delay in the median time pretreatment <em> versus </em> on-treatment was 1.3 days or a 16% reduction ( <em> P </em> = 0.04). <p id="x-x-p-4"> <em> Conclusions: </em> The wound angiogenesis assay used in this study was practical, well tolerated, and reproducible. Delays in wound angiogenesis because of BMS-275291 were detectable with this assay. This technique warrants additional investigation in clinical trials of other antiangiogenic agents. </p> </p> </p> </p></p>