Small E J, Baron A, Bok R
University of California-San Francisco Cancer Center, University of California 94115, USA.
Cancer. 1997 Nov 1;80(9):1755-9. doi: 10.1002/(sici)1097-0142(19971101)80:9<1755::aid-cncr9>3.0.co;2-d.
Although antiandrogen withdrawal has moderate efficacy in patients with hormone refractory prostate carcinoma (HRPC), the effect of the simultaneous suppression of adrenal androgens with ketoconazole at the time of antiandrogen withdrawal is not known.
Twenty consecutive patients with HRPC who had developed progressive disease despite combined androgen blockade were treated with antiandrogen withdrawal and simultaneous ketoconazole as a means of inhibiting adrenal steroid production. Prostate specific antigen (PSA) response was defined as a > 50% fall in PSA from baseline that was maintained for at least 8 weeks.
Ten patients had established metastatic disease, 2 had high PSAs and no imaging studies (PSA of 70 and 160 ng/mL, respectively), 3 had microscopically positive lymph nodes and serologic progression, and 5 had serologic progression alone. Overall, of 20 evaluable patients, 11 (55%) had a > 50% fall in PSA (95% confidence interval [CI], 31.5-76.9%). The median PSA response duration was 8.5 months (95% CI, 7-17 months). The median survival was 19 months. Toxicity was mild, with Grade 1 and 2 nausea and emesis in 15% of patients, Grade 1 fatigue in 10% of patients, and reversible Grade 1 or 2 hepatotoxicity in 10% of patients. Mild skin toxicity was observed in 20% of patients.
The addition of ketoconazole and hydrocortisone to antiandrogen withdrawal appears to increase the PSA response proportion observed with antiandrogen withdrawal alone. Toxicity is mild.
尽管抗雄激素撤药疗法对激素难治性前列腺癌（HRPC）患者有一定疗效，但在抗雄激素撤药时联合酮康唑抑制肾上腺雄激素的效果尚不清楚。
连续20例HRPC患者，尽管接受了联合雄激素阻断治疗仍出现疾病进展，接受抗雄激素撤药治疗，并同时使用酮康唑抑制肾上腺类固醇生成。前列腺特异性抗原（PSA）反应定义为PSA较基线水平下降>50%，且维持至少8周。
10例患者有明确的转移病灶，2例PSA水平高但未进行影像学检查（PSA分别为70和160 ng/mL），3例镜下淋巴结阳性且有血清学进展，5例仅有血清学进展。总体而言，20例可评估患者中，11例（55%）PSA下降>50%（95%置信区间[CI]，31.5 - 76.9%）。PSA反应持续时间的中位数为8.5个月（95% CI，7 - 17个月）。中位生存期为19个月。毒性较轻，15%的患者出现1级和2级恶心和呕吐，10%的患者出现1级疲劳，10%的患者出现可逆性1级或2级肝毒性。20%的患者观察到轻度皮肤毒性。
在抗雄激素撤药基础上加用酮康唑和氢化可的松似乎可提高单独使用抗雄激素撤药时观察到的PSA反应比例。毒性较轻。
