Pruthi Raj S, Derksen J Eric, Moore Dominic, Carson Culley C, Grigson Gayle, Watkins Cathy, Wallen Eric
Division of Urologic Surgery, Department of Biostatistics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2172-7. doi: 10.1158/1078-0432.CCR-05-2067.
Recent evidence has shown that cyclooxygenase-2 (COX-2) inhibitors have potent antitumor activity in prostate cancer both in vitro and in vivo. However, human trials are absent. This study evaluated the efficacy of the COX-2 inhibitor celecoxib in prostate-specific antigen (PSA) recurrent prostate cancer after radiation therapy (X-ray therapy or XRT) or radical prostatectomy.
Forty patients who had biochemical relapse after XRT or radical prostatectomy were treated with celecoxib 400 mg twice per day. Follow-up PSA levels were obtained at 3, 6, 12, and 18 months and subsequently every 6 months thereafter. Data were evaluated by calculating PSA doubling times and by calculating the slope of the curve of log(PSA) versus time to assess rate of PSA increase before and after celecoxib treatment for each patient.
Thirty-six of 40 (90%) patients had a slowing effect on their rate of PSA after 3 months, including 11 of 40 with a decline and 8 of 40 with stabilization of PSA. Short-term responses at 3 months continued at 6, 12, 18 months. Comparison of rate of PSA increase before versus after celecoxib treatment showed significant flattening of slope of log(PSA) versus time from pretreatment for each of the time points. 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 XRT or radical prostatectomy. These results suggest that COX-2 inhibitors may help delay or prevent disease progression in these patients and thereby help extend the time until androgen deprivation therapy.
最近有证据表明，环氧合酶-2（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。然而，尚无人体试验。本研究评估了COX-2抑制剂塞来昔布在放射治疗（X线治疗或XRT）或根治性前列腺切除术后前列腺特异性抗原（PSA）复发的前列腺癌中的疗效。
40例在XRT或根治性前列腺切除术后出现生化复发的患者，接受塞来昔布治疗，每日2次，每次400mg。在3、6、12和18个月时获取随访PSA水平，此后每6个月获取一次。通过计算PSA倍增时间以及计算log(PSA)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的增加速率。
40例患者中有36例（90%）在3个月后PSA速率有减缓作用，其中40例中有11例PSA下降，40例中有8例PSA稳定。3个月时的短期反应在6、12、18个月持续存在。比较塞来昔布治疗前后PSA增加速率，显示在每个时间点log(PSA)与时间的斜率较治疗前均显著变平。睾酮水平无显著变化，提示为非雄激素依赖机制。
COX-2抑制剂可能对XRT或根治性前列腺切除术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。
