A pilot surrogate endpoint biomarker study of celecoxib in oral premalignant lesions

Lori J. Wirth, Jeffrey F. Krane, Yi Li, Megan Othus, Amy E. Moran, David M. Dorfman, Charles M. Norris, Laura Goguen, Marshall R. Posner, Robert I. Haddad, Monica M. Bertagnolli

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

This study evaluated changes in prostaglandin E2 (PGE2) levels and related biomarkers in oral premalignant lesions (OPL) in response to celecoxib treatment. Twenty-two subjects were enrolled and treated with celecoxib. Pretreatment and 12-week biopsies were done. Subjects whose biopsy showed ≥30% decrease in PGE2 remained on celecoxib for a total of 12 months when repeat biopsy was done. Biopsies were examined to assess degree of dysplasia, DNA ploidy, and immunohistochemical expression of BCL2, pAKT-Ser473, Ki-67, and CD31 (microvessel density). In 18 paired biopsies available at baseline and 12 weeks, mean normalized PGE2 levels decreased by 38% (P = 0.002). After 12 months, PGE2 decreased by 31% (P = 0.340). Twelve biopsies (67%; P = 0.0129) showed improvement in degree of dysplasia after 12 weeks, and 8 of 11 biopsies (73%; P = 0.0703) continued to show an improvement in the degree of dysplasia after 12 months. Trends suggested down-modulation of cyclooxygenase-2 and Ki-67 in some tissues, increased pAKT-Ser473 expression, and an inverse relationship between PGE2 and BCL2 expression. This study documents the feasibility of measuring potential surrogate endpoint biomarkers of chemopreventive agent response in OPLs. Treatment with celecoxib in subjects with OPLs favorably modulates the primary mediator of cyclooxygenase-2 activity, PGE2, after 12 weeks.

Original languageEnglish (US)
Pages (from-to)339-348
Number of pages10
JournalCancer Prevention Research
Volume1
Issue number5
DOIs
StatePublished - Oct 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wirth, L. J., Krane, J. F., Li, Y., Othus, M., Moran, A. E., Dorfman, D. M., Norris, C. M., Goguen, L., Posner, M. R., Haddad, R. I., & Bertagnolli, M. M. (2008). A pilot surrogate endpoint biomarker study of celecoxib in oral premalignant lesions. Cancer Prevention Research, 1(5), 339-348. https://doi.org/10.1158/1940-6207.CAPR-07-0003