Jason F Flamiatos1, Tomasz M Beer2, Julie N Graff2,3, Kristine M Eilers2, Wei Tian4, Harman S Sekhon5, Mark Garzotto6,7. 1. School of Medicine, School of Public Health, Oregon Health and Science University, Portland, OR, USA. 2. Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. 3. Hospital and Specialty Medicine, VA Portland Health Care System, Portland, OR, USA. 4. Miraca Life Sciences, Irving, TX, USA. 5. Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada. 6. Department of Urology, Oregon Health and Science University, Portland, OR, USA. 7. Department of Urology and Radiation Medicine, VA Portland Health Care System, Portland, OR, USA.
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.
RCT Entities:
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.
Authors: Dipak Panigrahy; Allison Gartung; Jun Yang; Haixia Yang; Molly M Gilligan; Megan L Sulciner; Swati S Bhasin; Diane R Bielenberg; Jaimie Chang; Birgitta A Schmidt; Julia Piwowarski; Anna Fishbein; Dulce Soler-Ferran; Matthew A Sparks; Steven J Staffa; Vidula Sukhatme; Bruce D Hammock; Mark W Kieran; Sui Huang; Manoj Bhasin; Charles N Serhan; Vikas P Sukhatme Journal: J Clin Invest Date: 2019-06-17 Impact factor: 14.808
Authors: Anna Fishbein; Weicang Wang; Haixia Yang; Jun Yang; Victoria M Hallisey; Jianjun Deng; Sanne M L Verheul; Sung Hee Hwang; Allison Gartung; Yuxin Wang; Diane R Bielenberg; Sui Huang; Mark W Kieran; Bruce D Hammock; Dipak Panigrahy Journal: Proc Natl Acad Sci U S A Date: 2020-08-14 Impact factor: 11.205