Small E J, Baron A D, Fippin L, Apodaca D
Department of Medicine, University of California, San Francisco Cancer Center 94115, USA.
J Urol. 1997 Apr;157(4):1204-7.
We tested the hypothesis that certain patients with hormone refractory prostate cancer retain hormonal sensitivity even after progression following antiandrogen withdrawal. The efficacy of ketoconazole and hydrocortisone in this patient population was evaluated.
A total of 50 consecutive patients with advanced prostate cancer received ketoconazole and hydrocortisone at progression after antiandrogen withdrawal. Prostate specific antigen (PSA) response was defined as greater than a 50% decrease in PSA from baseline that was maintained for at least 8 weeks.
Overall, of 48 evaluable patients 30 (62.5%, 95% confidence interval 47.3 to 76.1%) had greater than a 50% decrease in PSA, while 23 (48%) had greater than an 80% decrease. The median duration of response was 3.5 months but 23 of 48 patients continue to exhibit a response, ranging from 3.25 to 12.75 or more months. The ketoconazole response rate in patients with no response to prior antiandrogen withdrawal was not different from that in patients with such a response (65 versus 40%, p = 0.35). Toxicity was mild. Grade 1 or 2 nausea, fatigue, edema, hepatotoxicity and rash occurred in 10.4 (5 of 48), 6.25, 6.25, 4.2 and 4.2% of patients, respectively, and anorexia occurred in 2%.
Failure to respond to antiandrogen withdrawal does not identify patients with truly hormone refractory disease. Ketoconazole retains significant activity in this setting and is extremely well tolerated.
我们检验了这样一个假设，即某些激素难治性前列腺癌患者即使在抗雄激素撤药后病情进展，仍保留激素敏感性。评估了酮康唑和氢化可的松在此类患者群体中的疗效。
共有50例晚期前列腺癌患者在抗雄激素撤药病情进展后接受酮康唑和氢化可的松治疗。前列腺特异性抗原（PSA）反应定义为PSA较基线水平降低超过50%，且维持至少8周。
总体而言，48例可评估患者中，30例（62.5%，95%置信区间47.3%至76.1%）PSA降低超过50%，23例（48%）PSA降低超过80%。反应的中位持续时间为3.5个月，但48例患者中有23例仍有反应，持续时间为3.25至12.75个月或更长。对先前抗雄激素撤药无反应的患者中酮康唑的反应率与有反应的患者无差异（65%对40%，p = 0.35）。毒性较轻。1级或2级恶心、疲劳、水肿、肝毒性和皮疹分别发生在10.4%（48例中的5例）、6.25%、6.25%、4.2%和4.2%的患者中，厌食发生在2%的患者中。
抗雄激素撤药无反应并不能识别真正的激素难治性疾病患者。酮康唑在此情况下仍保留显著活性，且耐受性极佳。
