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The impact of celecoxib on outcomes in advanced prostate cancer patients undergoing androgen deprivation therapy.

Recent work suggests the selective Cox-2 inhibitor celecoxib delays progression to androgen independence in hormone sensitive prostate cancer (HSPC) through inhibition of the androgen receptor (AR) and ErbB signaling. However, human studies examining its effect on delaying disease progression while on hormone therapy are limited. This study explores the effect of celecoxib use on PC survival in VA patients undergoing androgen deprivation therapy (ADT) for advanced PC. We retrospectively examined the association between celecoxib use (defined as duration of medication use ≥180 days) in men with PC being treated with ADT in national VA databases. Patients were diagnosed with PC from 2000-2008 and had follow-up through May 2016. Clinical, pathologic and demographic variables were compared by celecoxib use, using Mann-Whitney U test and Chi-squared tests. Associations between celecoxib use and overall survival (OS), skeletal related events (SRE), and cancer specific survival (CSS) were performed using adjusted Cox proportional hazard models. Overall, 87,344 patients with PC on ADT were identified. Patients on celecoxib (n=1,581) had lower PSA levels at both diagnosis (7.0 versus 8.7 ng/mL, P<0.001) and initiation of ADT (6.2 versus 7.3 ng/mL, P=0.002) compared to patients not taking celecoxib (n=85,763). Gleason score (P=0.14), death from PC (P=0.07), and number of SREs (P=0.18) were similar between groups. In the Cox multivariable analysis, celecoxib use was not associated with improved OS (hazard ratio, HR, 1.06, 95% confidence interval, CI, 0.93-1.21, P=0.38), risk of SRE (HR 0.95, 95% CI 0.62-1.44, P=0.80), or improved CSS (HR 1.00, 95% CI 0.78-1.28, P=0.98). Despite an association with lower PSA levels, celecoxib use in PC patients on ADT was not associated with improved cancer outcomes.

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