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

Abstract

4593 Purpose: COX-2 inhibitors have also been shown to have anti-neoplastic effects in a variety of tumor types including prostate cancer. This trial evaluated the efficacy of COX-2 inhibitor celecoxib in PSA-recurrent prostate cancer after radiation therapy (XRT) or radical prostatectomy (RP). Methods: 24 patients with rising PSA after definitive XRT (n=4) or RP (n=20) were treated with celecoxib at 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 an inhibitory effect on their serum PSA after 3 mos of treatment: 8/24 had a decline and 3/24 had stabilization of their PSA. Of the remaining 13 patients, 11 had slowing of their PSADT - mean increase (i.e. slowing) in PSADT of 4.5-fold from pre-treatment. Only 2 patients (12%) had no initial change in their PSADT at 3 mos., yet both patients eventually showed increase of PSADT (2.2-fold and 4.0-fold) by 12 mos. Short-term responses at 3 mos. continued at 6 and 12 mos. of treatment. There was a significant shift of patients with rapid towards slower/stable PSADT at all time points (p = 0.008) (table). Comparison of rate of PSA rise before vs. after celecoxib treatment showed significant flattening of mean 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 < 0.05 for each time point), There was no significant change in testosterone levels suggesting an androgen-independent mechanism. Conclusions: COX-2 inhibitors may decrease serum 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. No significant financial relationships to disclose.