title: A randomized controlled trial of celecoxib to prevent recurrence of nonmuscle-invasive bladder cancer.
abstract: Significant morbidity and expense result from frequent recurrences of nonmuscle-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 whether celecoxib could reduce the time-to-recurrence (TTR) in NMIBC patients at high risk for recurrence. A total of 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 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). However, celecoxib had a marginally significant effect on reducing metachronous recurrences (vs. placebo) with HR 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.
authors: Department of Medicine, Division of Hematology/Oncology, Baylor College of Medicine, Houston, Texas 77030, USA. sabichi@bcm.edu
authors: Anita L
authors: AL
authors: Sabichi
authors: J Jack
authors: JJ
authors: Lee
authors: H Barton
authors: HB
authors: Grossman
authors: Suyu
authors: S
authors: Liu
authors: Ellen
authors: E
authors: Richmond
authors: Bogdan A
authors: BA
authors: Czerniak
authors: Jorge
authors: J
authors: De la Cerda
authors: Craig
authors: C
authors: Eagle
authors: Jaye L
authors: JL
authors: Viner
authors: J Lynn
authors: JL
authors: Palmer
authors: Seth P
authors: SP
authors: Lerner
mesh_terms: D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control*; D009367:Neoplasm Staging; D010349:Patient Compliance; D011720:Pyrazoles / Q000627:therapeutic use*; D011788:Quality of Life; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib