低剂量酮康唑治疗中国去势抵抗性前列腺癌患者的疗效

[Efficacy of low dose ketoconazole therapy for Chinese patients with castration resistant prostate cancer].

作者信息

Lin Guo-wen, Ye Ding-wei, Yao Xu-dong, Zhang Shi-lin, Dai Bo, Zhang Hai-liang, Shen Yi-jun, Zhu Yao, Zhu Yi-ping, Shi Guo-hai, Ma Chun-guang, Xiao Wen-Jun, Qin Xiao-jian

机构信息

Department of Urology, Shanghai Cancer Center, Fudan University, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2012 Feb 28;92(8):520-3.

PMID:22490153

Abstract

OBJECTIVE

To assess the efficacy of low dose ketoconazole therapy for Chinese patients with castration resistant prostate cancer (CRPC) and explore possible prognosis factors.

METHODS

From August 2006 to August 2011, 71 patients with CRPC were analyzed retrospectively, who received oral ketoconazole 200 mg, three times a day with prednisone 5 mg, twice a day. Prostate specific antigen (PSA) response rate was defined as the percentage of patients with PSA decline ≥ 50% compared to baseline PSA level during low dose ketoconazole therapy. Multivariate Logistic regression analysis and receiver operating characteristic curve were used to assess the prognostic factors and their accuracy.

RESULTS

The mean initial serum PSA level was (205 ± 38) ng/ml for these patients with mean age (69 ± 1) years old. After first androgen deprivation therapy failure, the prostate cancer progressed into castration resistant stage. The baseline PSA was (93 ± 24) ng/ml and the baseline serum testosterone was (0.13 ± 0.02) ng/ml. During the low dose ketoconazole therapy, 31 patients (43.7%) had PSA decrease and 22 cases (31.0%) were effective with PSA decline more than 50%. PSA doubling time and baseline serum testosterone were positive correlation with PSA response rate by multivariate Logistic regression analysis. Patients with PSA doubling time of ≥ 3.0 months had a PSA response rate of 64.3% and the PSA response rate in those with < 3.0 months decreased to 22.8%, hazard rate (HR) = 0.149 (95% confidence interval [CI] 0.029 - 0.766), P = 0.023, area under the curve (AUC) = 0.707. The PSA response rate for patients with baseline serum testosterone ≥ 0.1 and < 0.1 µg/L were 55.6% and 5.7%, respectively, HR = 0.068 (95%CI 0.012 - 0.380), P = 0.002, AUC = 0.749. The common adverse reactions included liver dysfunction (17.9%), renal dysfunction (16.4%), fatigue (11.9%), nausea (6.0%) and anorexia (4.5%) and so on.

CONCLUSIONS

Low dose ketoconazole therapy was a moderate, low toxicity hormonal therapy option for patients with CRPC. PSA doubling time ≥ 3 months and baseline serum testosterone ≥ 0.1 µg/L were predictors of desired effect for low dose ketoconazole therapy.

摘要

目的

评估低剂量酮康唑治疗中国去势抵抗性前列腺癌（CRPC）患者的疗效，并探讨可能的预后因素。

方法

回顾性分析2006年8月至2011年8月期间71例CRPC患者，这些患者接受口服酮康唑200mg，每日3次，联合泼尼松5mg，每日2次。前列腺特异性抗原（PSA）反应率定义为低剂量酮康唑治疗期间PSA下降≥50%（相对于基线PSA水平）的患者百分比。采用多因素Logistic回归分析和受试者工作特征曲线评估预后因素及其准确性。

结果

这些患者的平均初始血清PSA水平为（205±38）ng/ml，平均年龄（69±1）岁。首次雄激素剥夺治疗失败后，前列腺癌进展至去势抵抗阶段。基线PSA为（93±24）ng/ml，基线血清睾酮为（0.13±0.02）ng/ml。在低剂量酮康唑治疗期间，31例患者（43.7%）PSA下降，22例（31.0%）有效，PSA下降超过50%。多因素Logistic回归分析显示，PSA倍增时间和基线血清睾酮与PSA反应率呈正相关。PSA倍增时间≥3.0个月的患者PSA反应率为64.3%，<3.0个月的患者PSA反应率降至22.8%，风险比（HR）=0.149（95%置信区间[CI]0.029 - 0.766），P = 0.023，曲线下面积（AUC）=0.707。基线血清睾酮≥0.1和<0.1μg/L的患者PSA反应率分别为55.6%和5.7%，HR = 0.068（95%CI 0.012 - 0.380），P = 0.002，AUC = 0.749。常见不良反应包括肝功能障碍（17.9%）、肾功能障碍（16.4%）、疲劳（11.9%）、恶心（6.0%）和厌食（4.5%）等。