A pilot study of use of the cyclooxygenase-2 inhibitor celecoxib in recurrent prostate cancer after definitive radiation therapy or radical prostatectomy.
OBJECTIVE
To evaluate the efficacy of the cyclooxygenase (COX)-2 inhibitor celecoxib in prostate-specific antigen (PSA) recurrent prostate cancer after definitive radiation therapy (RT) or radical prostatectomy (RP), as recent evidence showed that COX-2 inhibitors have potent antitumour activity in prostate cancer both in vitro and in vivo but there are no human trials.


METHODS
Twelve patients who had biochemical relapse after RT or RP were treated with celecoxib 200 mg twice daily. Follow-up PSA levels to assess efficacy were obtained at 3, 6 and 12 months after initiating treatment. Data were evaluated by calculating PSA doubling times and the slope of the curve of logPSA vs time, to assess rate of PSA rise before and after celecoxib treatment for each patient. Serum testosterone levels were also measured.


RESULTS
Eight of the 12 patients had significant inhibition of their serum PSA levels after 3 months of treatment; five had a decline in their absolute PSA level and three a stabilization of the level. Of the remaining four patients, three had a marked decrease in their PSA doubling time, with a mean increase (i.e. slowing) of 3.1 times that before treatment. The short-term responses at 3 months also continued at 6 and 12 months. From the slope of log PSA vs time there was a significant flattening of the rate of PSA rise (P = 0.001). There was a significant change of patients with rapid doubling times towards slower doubling times or even stable/declining PSA values after treatment with celecoxib (P = 0.029). There was no significant change in testosterone levels, suggesting an androgen-independent mechanism.


CONCLUSIONS
COX-2 inhibitors may have an effect on serum PSA levels in patients with biochemical progression after RT or RP. These results suggest that COX-2 inhibitors may help to delay or prevent disease progression in these patients, and thereby help extend the time until androgen deprivation therapy. Further study with more patients is currently underway to better evaluate the clinical potential of COX-2 inhibitors as an antitumour agents in prostate cancer.
Pruthi
R S
RS
Division of Urologic Surgery, The University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Derksen
J E
JE
Moore
D
D
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068579:Celecoxib; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004341:Drug Evaluation; D005500:Follow-Up Studies; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010865:Pilot Projects; D011451:Prostaglandin-Endoperoxide Synthases; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D011720:Pyrazoles; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D017430:Prostate-Specific Antigen; D000068579:Celecoxib