A phase II trial of celecoxib in PSA recurrent prostate cancer after definitive radiation therapy (XRT) or radical prostatectomy (RP)

Abstract

Abstract Introduction: COX-2 inhibitors may have anti-neoplastic effects in a variety of tumor types including prostate cancer. We evaluated the efficacy of celecoxib in PSA-recurrent prostate cancer after XRT or RP. Methods: 24 patients with rising PSA after XRT (n = 4) or RP (n = 20) were treated with celecoxib 400 mg/day (n = 12) or 800 mg/day (n = 12) (bid dosing). PSA levels were obtained at 3, 6, and 12 months after initiation of treatment. Data was evaluated by calculating 1) PSA doubling times (PSADT) and 2) slope of logPSA vs. time before and after celecoxib treatment at each time point. Testosterone levels were also obtained. Results: 22 of 24 (92%) patients had inhibitory effect on their PSA after 3 mos of treatment:8/24 had decline and 3/24 had stabilization of their PSA. Of the remaining 13, 11 had slowing of PSADT-mean increase (i.e. slowing) of PSADT was 4.5-fold from pre-treatment. Only 2 patients had no initial change in PSADT at 3 mos., yet both eventually showed increase of PSADT (2.2-fold, 4.0-fold) by 12 mos. There was a significant shift of patients with rapid towards slower/stable PSADT at all time points (p = 0.008; see table). Comparison of PSA rise before vs. after celecoxib treatment showed significant flattening of slope of logPSA vs. time from pre-treatment (1.48) vs. 3 mos. (0.09), 6 mos. (0.35) and 12 mos. (0.46) (p High Moderate Slow Stable/decline Pre 11/24 6/24 7/24 0/24 3 m 1/24 1/24 11/24 11/24 6 m 1/24 4/24 11/24 8/24 12 m 1/24 3/24 18/24 2/24 Conclusions: COX-2 inhibitors may decrease PSA levels in patients with biochemical progression after XRT or RP. These results suggest that COX-2 inhibitors may help delay disease progression in these patients.