Small Eric J, Halabi Susan, Dawson Nancy A, Stadler Walter M, Rini Brian I, Picus Joel, Gable Preston, Torti Frank M, Kaplan Ellen, Vogelzang Nicholas J
UCSF Comprehensive Cancer Center, University of California San Francisco, 1600 Divisadero St, Room A-718, San Francisco, CA 94115, USA.
J Clin Oncol. 2004 Mar 15;22(6):1025-33. doi: 10.1200/JCO.2004.06.037.
Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of > or =50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy.
AiPCa patients were randomized to undergo AAWD alone (n=132), or together with K (400 mg orally [p.o.] tid) and hydrocortisone (30 mg p.o. each morning, 10 mg p.o. each evening; n=128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K.
Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P=.0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P=.02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression.
K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.
抗雄激素撤药（AAWD）可使15%至30%的雄激素非依赖性前列腺癌（AiPCa）患者出现前列腺特异性抗原（PSA）反应（PSA水平下降≥50%）。此后，通常会使用酮康唑（K）等药物进行肾上腺雄激素消融。比较了单独AAWD与同时进行AAWD和K治疗的疗效。
将AiPCa患者随机分为单独接受AAWD治疗组（n = 132），或同时接受K（口服400 mg，每日三次）和氢化可的松（每日早晨口服30 mg，每晚口服10 mg；n = 128）治疗组。单独接受AAWD治疗后出现疾病进展的患者有资格接受K的延期治疗。
单独接受AAWD治疗的患者中有11%出现PSA反应，而同时接受AAWD和K治疗的患者中有27%出现PSA反应（P = 0.0002）。单独接受AAWD治疗的患者中有2%观察到客观反应，而接受AAWD/K治疗的患者中有20%观察到客观反应（P = 0.02）。生存率无差异。接受延期K治疗的患者中分别有32%和7%观察到PSA和客观反应，且在既往有AAWD反应的患者中更常见。K治疗耐受性良好，导致肾上腺雄激素水平下降，在疾病进展时升高。
K在AiPCa患者中具有适度活性，而单独AAWD活性极小。肾上腺雄激素水平在K治疗时下降，然后在疾病进展时上升，提示在接受K治疗时疾病进展可能是由于对K的肾上腺溶解特性产生快速耐受。
