Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor
Date of Publication
Clinical Cancer Research
Purpose: 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.
Experimental Design: 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.
Results: 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 (2.2–6.9) and 8.0 (5.0–10.0) pretreatment whereas on-treatment the values were 4.9 (3.7–8.0) and 9.3 (7.0–11.5), 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 (P = 0.06). For the target AVS of 2.0 the delay in the median time pretreatment versus on-treatment was 1.3 days or a 16% reduction (P = 0.04).
Conclusions: 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.
Lockhart, A. C.; Braun, R. D.; Yu, D.; Ross, J. R.; Dewhirst, M. W.; Humphrey, J. S.; Thompson, S.; Williams, K. M.; Klitzman, B.; Yuan, F.; Grichnik, J. M.; Proia, A. D.; Conway, D. A.; and Hurwitz, H. I., "Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor" (2003). Osteopathic Medicine, Jerry M. Wallace School of. 296.