A Randomized Controlled Trial of Celecoxib to Prevent Recurrence of Nonmuscle-Invasive Bladder Cancer

Abstract

Significant morbidity and expense result from frequent recurrences of non-muscle invasive bladder cancer (NMIBC) after standard treatment, and carcinoma in situ (Tis) is a poor prognostic factor. Predicated on observational and preclinical data strongly supporting cyclooxygenase-2 (COX-2) in the pathogenesis, and the activity of COX-2 inhibitors, in bladder cancer, we conducted a randomized, double-blind, placebo-controlled trial to determine if celecoxib could reduce the time-to-recurrence (TTR) in NMIBC patients at high risk for recurrence. 146 patients were randomized to celecoxib (200 mg) or placebo orally twice daily for at least 12 months. The average treatment duration was 1.25 years. Primary intent-to-treat analysis revealed celecoxib did not statistically significantly prolong TTR compared with placebo (P = 0.17, log-rank). With a median follow-up of 2.49 years the relative risk of recurrence in the celecoxib vs placebo arms was 0.64 (95% CI, 0.38, 1.17). The recurrence-free rate at 12 months with celecoxib was 88% (95% CI, 0.81,0.96) versus 78% (95% CI, 0.69, 0.89) with placebo. After controlling for covariates with Cox regression analysis, recurrence rates did not differ between the two study arms (HR = 0.69; 95% CI, 0.37,1.29). Celecoxib had a marginally significant effect on reducing metachronous recurrences (vs. placebo) with hazard ratio of 0.56 (95% CI, 0.3,1.06; P=0.075). Celecoxib was well tolerated, with similar adverse events and quality-of-life in both arms. Our clinical trial results do not show a clinical benefit for celecoxib in preventing NMIBC recurrence but further investigation of COX-2 inhibitors in this setting is warranted.

Celecoxib Enhances Radiosensitivity via Induction of G₂-M Phase Arrest and Apoptosis in Nasopharyngeal Carcinoma

“…NSAIDs could suppress COX-2 expression and prevent the effects of prostaglandins. Celecoxib, the first selective COX-2 inhibitor approved by the U.S. Food and Drug Administration, has been reported to prevent carcinogenesis in both animals and humans [11,12,13]. Moreover, it has been reported that the chemotherapy, including celecoxib when used at low dose, may be able to enhance the efficacy of radiation treatment on the cancer cells [14,15,16].…”

Chemoprevention of Urothelial Cell Carcinoma Growth and Invasion by the Dual COX–LOX Inhibitor Licofelone in UPII-SV40T Transgenic Mice

“…Sabichi et al . (32) did not observe a clinical benefit of celecoxib in preventing recurrence of non-muscle-invasive bladder cancer in a randomized controlled trial, although, celecoxib had a marginally significant effect on reducing metachronous recurrences compared with placebo. However, nimesulide was capable of preventing bladder tumor recurrences in a dose-dependent manner (28).…”

Efficacy comparison of lyophilised black raspberries and combination of celecoxib and PBIT in prevention of carcinogen-induced oesophageal cancer in rats

“…Celecoxib, a selective COX-2 inhibitor, has been widely evaluated in numerous preclinical studies and human clinical trials for potential chemopreventive activity for cancers of colon, bladder, head and neck, skin and esophagus (Bertagnolli et al, 2006; Elmets et al, 2010; Limburg et al, 2005; Sabichi et al, 2011; Shin et al, 2013). Unfortunately, the potential for toxicity, particularly cardiac, may limit the use of COX-2 inhibitors for chemoprevention with the exception of the most high risk cohorts (Solomon et al, 2005).…”