Pruthi R S, Derksen J E, Moore D
Division of Urologic Surgery, The University of North Carolina, Chapel Hill, North Carolina 27599, USA.
BJU Int. 2004 Feb;93(3):275-8. doi: 10.1111/j.1464-410x.2004.04601.x.
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.
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.
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.
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.
评估环氧化酶（COX）-2抑制剂塞来昔布在根治性放射治疗（RT）或根治性前列腺切除术（RP）后前列腺特异性抗原（PSA）复发的前列腺癌中的疗效，因为最近有证据表明COX-2抑制剂在体外和体内对前列腺癌均具有强大的抗肿瘤活性，但尚无人体试验。
12例RT或RP后发生生化复发的患者接受塞来昔布治疗，每日2次，每次200mg。在开始治疗后的3、6和12个月获取随访PSA水平以评估疗效。通过计算PSA倍增时间以及logPSA与时间曲线的斜率来评估数据，以评估每位患者在塞来昔布治疗前后PSA升高的速率。还测量了血清睾酮水平。
12例患者中有8例在治疗3个月后血清PSA水平受到显著抑制；5例患者的绝对PSA水平下降，3例患者的PSA水平稳定。其余4例患者中，3例患者的PSA倍增时间显著缩短，平均增加（即减慢）至治疗前的3.1倍。3个月时的短期反应在6个月和12个月时也持续存在。从log PSA与时间的斜率来看，PSA升高速率显著变平缓（P = 0.001）。塞来昔布治疗后，PSA倍增时间快的患者向较慢的倍增时间甚至稳定/下降的PSA值转变有显著变化（P = 0.029）。睾酮水平无显著变化，提示存在非雄激素依赖机制。
COX-2抑制剂可能对RT或RP后生化进展患者的血清PSA水平有影响。这些结果表明，COX-2抑制剂可能有助于延缓或预防这些患者的疾病进展，从而有助于延长至雄激素剥夺治疗的时间。目前正在对更多患者进行进一步研究，以更好地评估COX-2抑制剂作为前列腺癌抗肿瘤药物的临床潜力。
