A stratified randomized double-blind phase II trial of celecoxib for treating patients with cervical intraepithelial neoplasia

The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study

Janet S. Rader, Michael W. Sill, Jan H. Beumer, Heather A. Lankes, Doris Mangiaracina Benbrook, Francisco A Garcia, Connie Trimble, J. Tate Thigpen, Richard Lieberman, Rosemary E. Zuna, Charles A. Leath, Nick M. Spirtos, John Byron, Premal H. Thaker, Shashikant Lele, David S Alberts

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: To examine the effect of celecoxib on cervical intraepithelial neoplasia 3 (CIN 3). This is a NRG Oncology/Gynecologic Oncology Group study with translational biomarkers. Patients and methods: Patients with CIN 3 were randomized to celecoxib 400. mg once daily (67 patients) or placebo (63 patients) for 14-18. weeks. The primary outcome measure was histologic regression. A test of equal probabilities of success between two therapies was conducted, using Fisher's Exact Test at alpha = 10% and 90% power when the treatment arm boosted the probability of success by 30%. Translational analysis included cervical tissue HPV genotyping, COX-2 expression in biopsies, and serum celecoxib and VEGF levels. Results: In primary analysis, histologic regression was not significantly higher in the celecoxib group (40%) than in the placebo group (34.1%). However, exploratory analyses suggest patients with high serum VEGF levels exhibited greater regression in the celecoxib arm (47.3%) than in the placebo arm (14.3%). Regression rates were similar by treatment group in patients with low VEGF. VEGF levels increased over time in the placebo group, but remained the same in the treatment group. COX-2 expression in cervical biopsies declined from pre-treatment to the end of treatment with celecoxib; it did not change with placebo. Conclusions: Celecoxib at 400. mg once daily for 14-18. weeks did not significantly decrease the severity of CIN 3 compared with placebo except, possibly, in subjects with high baseline VEGF. Therefore, serum VEGF levels might identify patients who may benefit from celecoxib or other therapies, personalizing future chemoprevention trials for CIN 3.

Original languageEnglish (US)
JournalGynecologic Oncology
DOIs
StateAccepted/In press - Dec 20 2016

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Celecoxib
Cervical Intraepithelial Neoplasia
Vascular Endothelial Growth Factor A
Placebos
Serum
Therapeutics
Biopsy
Chemoprevention

Keywords

  • Celecoxib
  • Cervix
  • Chemoprevention
  • CIN 3
  • COX-2
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

A stratified randomized double-blind phase II trial of celecoxib for treating patients with cervical intraepithelial neoplasia : The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study. / Rader, Janet S.; Sill, Michael W.; Beumer, Jan H.; Lankes, Heather A.; Benbrook, Doris Mangiaracina; Garcia, Francisco A; Trimble, Connie; Tate Thigpen, J.; Lieberman, Richard; Zuna, Rosemary E.; Leath, Charles A.; Spirtos, Nick M.; Byron, John; Thaker, Premal H.; Lele, Shashikant; Alberts, David S.

In: Gynecologic Oncology, 20.12.2016.

Research output: Contribution to journalArticle

Rader, Janet S. ; Sill, Michael W. ; Beumer, Jan H. ; Lankes, Heather A. ; Benbrook, Doris Mangiaracina ; Garcia, Francisco A ; Trimble, Connie ; Tate Thigpen, J. ; Lieberman, Richard ; Zuna, Rosemary E. ; Leath, Charles A. ; Spirtos, Nick M. ; Byron, John ; Thaker, Premal H. ; Lele, Shashikant ; Alberts, David S. / A stratified randomized double-blind phase II trial of celecoxib for treating patients with cervical intraepithelial neoplasia : The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study. In: Gynecologic Oncology. 2016.
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abstract = "Purpose: To examine the effect of celecoxib on cervical intraepithelial neoplasia 3 (CIN 3). This is a NRG Oncology/Gynecologic Oncology Group study with translational biomarkers. Patients and methods: Patients with CIN 3 were randomized to celecoxib 400. mg once daily (67 patients) or placebo (63 patients) for 14-18. weeks. The primary outcome measure was histologic regression. A test of equal probabilities of success between two therapies was conducted, using Fisher's Exact Test at alpha = 10{\%} and 90{\%} power when the treatment arm boosted the probability of success by 30{\%}. Translational analysis included cervical tissue HPV genotyping, COX-2 expression in biopsies, and serum celecoxib and VEGF levels. Results: In primary analysis, histologic regression was not significantly higher in the celecoxib group (40{\%}) than in the placebo group (34.1{\%}). However, exploratory analyses suggest patients with high serum VEGF levels exhibited greater regression in the celecoxib arm (47.3{\%}) than in the placebo arm (14.3{\%}). Regression rates were similar by treatment group in patients with low VEGF. VEGF levels increased over time in the placebo group, but remained the same in the treatment group. COX-2 expression in cervical biopsies declined from pre-treatment to the end of treatment with celecoxib; it did not change with placebo. Conclusions: Celecoxib at 400. mg once daily for 14-18. weeks did not significantly decrease the severity of CIN 3 compared with placebo except, possibly, in subjects with high baseline VEGF. Therefore, serum VEGF levels might identify patients who may benefit from celecoxib or other therapies, personalizing future chemoprevention trials for CIN 3.",
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T2 - The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study

AU - Rader, Janet S.

AU - Sill, Michael W.

AU - Beumer, Jan H.

AU - Lankes, Heather A.

AU - Benbrook, Doris Mangiaracina

AU - Garcia, Francisco A

AU - Trimble, Connie

AU - Tate Thigpen, J.

AU - Lieberman, Richard

AU - Zuna, Rosemary E.

AU - Leath, Charles A.

AU - Spirtos, Nick M.

AU - Byron, John

AU - Thaker, Premal H.

AU - Lele, Shashikant

AU - Alberts, David S

PY - 2016/12/20

Y1 - 2016/12/20

N2 - Purpose: To examine the effect of celecoxib on cervical intraepithelial neoplasia 3 (CIN 3). This is a NRG Oncology/Gynecologic Oncology Group study with translational biomarkers. Patients and methods: Patients with CIN 3 were randomized to celecoxib 400. mg once daily (67 patients) or placebo (63 patients) for 14-18. weeks. The primary outcome measure was histologic regression. A test of equal probabilities of success between two therapies was conducted, using Fisher's Exact Test at alpha = 10% and 90% power when the treatment arm boosted the probability of success by 30%. Translational analysis included cervical tissue HPV genotyping, COX-2 expression in biopsies, and serum celecoxib and VEGF levels. Results: In primary analysis, histologic regression was not significantly higher in the celecoxib group (40%) than in the placebo group (34.1%). However, exploratory analyses suggest patients with high serum VEGF levels exhibited greater regression in the celecoxib arm (47.3%) than in the placebo arm (14.3%). Regression rates were similar by treatment group in patients with low VEGF. VEGF levels increased over time in the placebo group, but remained the same in the treatment group. COX-2 expression in cervical biopsies declined from pre-treatment to the end of treatment with celecoxib; it did not change with placebo. Conclusions: Celecoxib at 400. mg once daily for 14-18. weeks did not significantly decrease the severity of CIN 3 compared with placebo except, possibly, in subjects with high baseline VEGF. Therefore, serum VEGF levels might identify patients who may benefit from celecoxib or other therapies, personalizing future chemoprevention trials for CIN 3.

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KW - CIN 3

KW - COX-2

KW - VEGF

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