Cancer Prevention Research CR Magazine AM No Deadline
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Cancer Prevention Research 1, 339, October 1, 2008. doi: 10.1158/1940-6207.CAPR-07-0003
© 2008 American Association for Cancer Research
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Research Articles

A Pilot Surrogate Endpoint Biomarker Study of Celecoxib in Oral Premalignant Lesions

Lori J. Wirth1, Jeffrey F. Krane3, Yi Li2, Megan Othus2, Amy E. Moran4, David M. Dorfman3, Charles M. Norris, Jr4, Laura Goguen4, Marshall R. Posner1, Robert I. Haddad1 and Monica M. Bertagnolli4

Authors' Affiliations: Departments of 1 Adult Oncology and 2 Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School; Departments of 3 Pathology and 4 Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Requests for reprints: Monica M. Bertagnolli, Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Phone: 617-732-8910; Fax: 617-582-6177; E-mail: mbertagnolli{at}partners.org.

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.

Key Words: PGE2 • COX-2 • chemoprevention • oral leukoplakia


Commentary

Assessing Efficacy in Early-Phase Cancer Prevention Trials: The Case of Oral Premalignancy
Eva Szabo
Cancer Prevention Research 2008 1: 312-315. [Full Text] [PDF]



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E. Szabo
Assessing Efficacy in Early-Phase Cancer Prevention Trials: The Case of Oral Premalignancy
Cancer Prevention Research, October 1, 2008; 1(5): 312 - 315.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.