Cyclooxygenase-2 (COX-2) inhibition for prostate cancer chemoprevention: Double-blind randomised study of pre-prostatectomy celecoxib or placebo

Jason F. Flamiatos, Tomasz (Tom) Beer, Julie Graff, Kristine M. Eilers, Wei Tian, Harman S. Sekhon, Mark Garzotto

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: To evaluate the biological effects of selective cyclooxygenase-2 inhibition on prostate tissue in patients undergoing radical prostatectomy (RP). Patients and Methods: Patients with localised prostate cancer were randomised to receive either celecoxib 400 mg twice daily or placebo for 4 weeks before RP. Specimens were analysed for levels of apoptosis, prostaglandins, and androgen receptor (AR). Effects on serum prostate-specific antigen (PSA) and postoperative opioid use were also measured. Results: In all, 28 of 44 anticipated patients enrolled and completed treatment. One patient in the celecoxib arm had a myocardial infarction postoperatively. For this reason, and safety concerns in other studies, enrolment was halted. The apoptosis index (AI) in tumour cells was 0.29% [95% confidence interval (CI) 0.11-0.47%] vs 0.39% (95% CI 0.00-0.84%) in the celecoxib and placebo arms, respectively (P = 0.68). The AI in benign cells was 0.18% (95% CI 0.03-0.32%) vs 0.13% (95% CI 0.00-0.28%) in the celecoxib and placebo arms, respectively (P = 0.67). Prostaglandin E2 and AR levels were similar in cancerous and benign tissues when comparing the two arms. The median baseline PSA level was 6.0 and 6.2 ng/mL for the celecoxib and placebo groups, respectively, and did not significantly change after celecoxib treatment. There was no difference in postoperative opiate usage between arms. Conclusion: Celecoxib had no effect on apoptosis, prostaglandins or AR levels in cancerous or benign prostate tissues. These findings coupled with drug safety concerns should serve to limit interest in these selective drugs as chemopreventive agents.

Original languageEnglish (US)
JournalBJU International
DOIs
StateAccepted/In press - 2016

Fingerprint

Celecoxib
Chemoprevention
Cyclooxygenase 2
Prostatectomy
Double-Blind Method
Prostatic Neoplasms
Placebos
Prostaglandin Receptors
Androgen Receptors
Confidence Intervals
Apoptosis
Prostate-Specific Antigen
Opiate Alkaloids
Prostate
Safety
Dinoprostone
Pharmaceutical Preparations
Opioid Analgesics

Keywords

  • Celecoxib
  • Chemoprevention
  • COX-2 inhibitors
  • NSAIDs
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

Cite this

@article{07ba6d0569fd4532b8cf77a9d1fb6ad2,
title = "Cyclooxygenase-2 (COX-2) inhibition for prostate cancer chemoprevention: Double-blind randomised study of pre-prostatectomy celecoxib or placebo",
abstract = "Objective: To evaluate the biological effects of selective cyclooxygenase-2 inhibition on prostate tissue in patients undergoing radical prostatectomy (RP). Patients and Methods: Patients with localised prostate cancer were randomised to receive either celecoxib 400 mg twice daily or placebo for 4 weeks before RP. Specimens were analysed for levels of apoptosis, prostaglandins, and androgen receptor (AR). Effects on serum prostate-specific antigen (PSA) and postoperative opioid use were also measured. Results: In all, 28 of 44 anticipated patients enrolled and completed treatment. One patient in the celecoxib arm had a myocardial infarction postoperatively. For this reason, and safety concerns in other studies, enrolment was halted. The apoptosis index (AI) in tumour cells was 0.29{\%} [95{\%} confidence interval (CI) 0.11-0.47{\%}] vs 0.39{\%} (95{\%} CI 0.00-0.84{\%}) in the celecoxib and placebo arms, respectively (P = 0.68). The AI in benign cells was 0.18{\%} (95{\%} CI 0.03-0.32{\%}) vs 0.13{\%} (95{\%} CI 0.00-0.28{\%}) in the celecoxib and placebo arms, respectively (P = 0.67). Prostaglandin E2 and AR levels were similar in cancerous and benign tissues when comparing the two arms. The median baseline PSA level was 6.0 and 6.2 ng/mL for the celecoxib and placebo groups, respectively, and did not significantly change after celecoxib treatment. There was no difference in postoperative opiate usage between arms. Conclusion: Celecoxib had no effect on apoptosis, prostaglandins or AR levels in cancerous or benign prostate tissues. These findings coupled with drug safety concerns should serve to limit interest in these selective drugs as chemopreventive agents.",
keywords = "Celecoxib, Chemoprevention, COX-2 inhibitors, NSAIDs, Prostate cancer",
author = "Flamiatos, {Jason F.} and Beer, {Tomasz (Tom)} and Julie Graff and Eilers, {Kristine M.} and Wei Tian and Sekhon, {Harman S.} and Mark Garzotto",
year = "2016",
doi = "10.1111/bju.13612",
language = "English (US)",
journal = "BJU International",
issn = "1464-4096",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Cyclooxygenase-2 (COX-2) inhibition for prostate cancer chemoprevention

T2 - Double-blind randomised study of pre-prostatectomy celecoxib or placebo

AU - Flamiatos, Jason F.

AU - Beer, Tomasz (Tom)

AU - Graff, Julie

AU - Eilers, Kristine M.

AU - Tian, Wei

AU - Sekhon, Harman S.

AU - Garzotto, Mark

PY - 2016

Y1 - 2016

N2 - Objective: To evaluate the biological effects of selective cyclooxygenase-2 inhibition on prostate tissue in patients undergoing radical prostatectomy (RP). Patients and Methods: Patients with localised prostate cancer were randomised to receive either celecoxib 400 mg twice daily or placebo for 4 weeks before RP. Specimens were analysed for levels of apoptosis, prostaglandins, and androgen receptor (AR). Effects on serum prostate-specific antigen (PSA) and postoperative opioid use were also measured. Results: In all, 28 of 44 anticipated patients enrolled and completed treatment. One patient in the celecoxib arm had a myocardial infarction postoperatively. For this reason, and safety concerns in other studies, enrolment was halted. The apoptosis index (AI) in tumour cells was 0.29% [95% confidence interval (CI) 0.11-0.47%] vs 0.39% (95% CI 0.00-0.84%) in the celecoxib and placebo arms, respectively (P = 0.68). The AI in benign cells was 0.18% (95% CI 0.03-0.32%) vs 0.13% (95% CI 0.00-0.28%) in the celecoxib and placebo arms, respectively (P = 0.67). Prostaglandin E2 and AR levels were similar in cancerous and benign tissues when comparing the two arms. The median baseline PSA level was 6.0 and 6.2 ng/mL for the celecoxib and placebo groups, respectively, and did not significantly change after celecoxib treatment. There was no difference in postoperative opiate usage between arms. Conclusion: Celecoxib had no effect on apoptosis, prostaglandins or AR levels in cancerous or benign prostate tissues. These findings coupled with drug safety concerns should serve to limit interest in these selective drugs as chemopreventive agents.

AB - Objective: To evaluate the biological effects of selective cyclooxygenase-2 inhibition on prostate tissue in patients undergoing radical prostatectomy (RP). Patients and Methods: Patients with localised prostate cancer were randomised to receive either celecoxib 400 mg twice daily or placebo for 4 weeks before RP. Specimens were analysed for levels of apoptosis, prostaglandins, and androgen receptor (AR). Effects on serum prostate-specific antigen (PSA) and postoperative opioid use were also measured. Results: In all, 28 of 44 anticipated patients enrolled and completed treatment. One patient in the celecoxib arm had a myocardial infarction postoperatively. For this reason, and safety concerns in other studies, enrolment was halted. The apoptosis index (AI) in tumour cells was 0.29% [95% confidence interval (CI) 0.11-0.47%] vs 0.39% (95% CI 0.00-0.84%) in the celecoxib and placebo arms, respectively (P = 0.68). The AI in benign cells was 0.18% (95% CI 0.03-0.32%) vs 0.13% (95% CI 0.00-0.28%) in the celecoxib and placebo arms, respectively (P = 0.67). Prostaglandin E2 and AR levels were similar in cancerous and benign tissues when comparing the two arms. The median baseline PSA level was 6.0 and 6.2 ng/mL for the celecoxib and placebo groups, respectively, and did not significantly change after celecoxib treatment. There was no difference in postoperative opiate usage between arms. Conclusion: Celecoxib had no effect on apoptosis, prostaglandins or AR levels in cancerous or benign prostate tissues. These findings coupled with drug safety concerns should serve to limit interest in these selective drugs as chemopreventive agents.

KW - Celecoxib

KW - Chemoprevention

KW - COX-2 inhibitors

KW - NSAIDs

KW - Prostate cancer

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DO - 10.1111/bju.13612

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