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

作者：Sabichi Anita L^*; Lee J Jack; Grossman H Barton; Liu Suyu; Richmond Ellen; Czerniak Bogdan A; De la Cerda Jorge; Eagle Craig; Viner Jaye L; Palmer J Lynn; Lerner Seth P

来源：Cancer Prevention Research, 2011, 4(10): 1580-1589.

DOI：10.1158/1940-6207.CAPR-11-0036

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 meta-chronous 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. Cancer Prev Res; 4(10); 1580-9.

• 出版日期2011-10