Publications [#134188] of Mark W. Dewhirst
- AC Lockhart, RD Braun, D Yu, JR Ross, MW Dewhirst, JS Humphrey, S Thompson, KM Williams, B Klitzman, F Yuan, JM Grichnik, AD Proia, DA Conway, HI Hurwitz, Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor.,
Clinical cancer research : an official journal of the American Association for Cancer Research, vol. 9 no. 2
pp. 586-93, ISSN 1078-0432
(last updated on 2013/05/16)
OBJECTIVE: 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. METHODS: 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.
Antineoplastic Agents • Biopsy • Humans • Imidazoles • Matrix Metalloproteinase Inhibitors* • Neoplasms • Neovascularization, Pathologic • Organic Chemicals* • Survival Analysis • Time Factors • adverse effects* • blood supply* • drug therapy • mortality • pathology • prevention & control*