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

Publication ,  Journal Article
Lockhart, AC; Braun, RD; Yu, D; Ross, JR; Dewhirst, MW; Humphrey, JS; Thompson, S; Williams, KM; Klitzman, B; Yuan, F; Grichnik, JM; Proia, AD ...
Published in: Clin Cancer Res
February 2003

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.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

February 2003

Volume

9

Issue

2

Start / End Page

586 / 593

Location

United States

Related Subject Headings

  • Time Factors
  • Survival Analysis
  • Organic Chemicals
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Neoplasms
  • Matrix Metalloproteinase Inhibitors
  • Imidazoles
  • Humans
  • Biopsy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lockhart, A. C., Braun, R. D., Yu, D., Ross, J. R., Dewhirst, M. W., Humphrey, J. S., … Hurwitz, H. I. (2003). Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor. Clin Cancer Res, 9(2), 586–593.
Lockhart, A Craig, Rod D. Braun, Daohai Yu, Joel R. Ross, Mark W. Dewhirst, Jeffrey S. Humphrey, Seth Thompson, et al. “Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor.Clin Cancer Res 9, no. 2 (February 2003): 586–93.
Lockhart AC, Braun RD, Yu D, Ross JR, Dewhirst MW, Humphrey JS, et al. Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor. Clin Cancer Res. 2003 Feb;9(2):586–93.
Lockhart, A. Craig, et al. “Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor.Clin Cancer Res, vol. 9, no. 2, Feb. 2003, pp. 586–93.
Lockhart AC, Braun RD, Yu D, Ross JR, Dewhirst MW, Humphrey JS, Thompson S, Williams KM, Klitzman B, Yuan F, Grichnik JM, Proia AD, Conway DA, Hurwitz HI. Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor. Clin Cancer Res. 2003 Feb;9(2):586–593.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

February 2003

Volume

9

Issue

2

Start / End Page

586 / 593

Location

United States

Related Subject Headings

  • Time Factors
  • Survival Analysis
  • Organic Chemicals
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Neoplasms
  • Matrix Metalloproteinase Inhibitors
  • Imidazoles
  • Humans
  • Biopsy