对“多西他赛难治性转移性去势抵抗性前列腺癌患者中醋酸阿比特龙与酮康唑的比较”的评论。Peer A、Gottfried M、Sinibaldi V、Carducci MA、Eisenberger MA、Sella A、Leibowitz-Amit R、Berger R、Keizman D，以色列海法兰巴姆医疗中心肿瘤科。：《前列腺》2014年4月；74(4)：433 - 440；doi:10.1002/pros.22765。[2013年12月11日在线发表]

Commentary on "Comparison of abiraterone acetate versus ketoconazole in patients with metastatic castration resistant prostate cancer refractory to docetaxel." Peer A, Gottfried M, Sinibaldi V, Carducci MA, Eisenberger MA, Sella A, Leibowitz-Amit R, Berger R, Keizman D, Department of Oncology, Rambam Medical Center, Haifa, Israel.: Prostate 2014 Apr;74(4):433-40; doi:10.1002/pros.22765. [Epub 2013 Dec 11].

作者信息

Trump Donald

出版信息

Urol Oncol. 2016 May;34(5):247. doi: 10.1016/j.urolonc.2015.02.008. Epub 2015 Apr 20.

DOI:10.1016/j.urolonc.2015.02.008

PMID:25907623

Abstract

BACKGROUND

Abiraterone, a potent CYP 17 inhibitor, is standard treatment in docetaxel refractory, metastatic castrate resistant prostate cancer (mCRPC). However, in countries where abiraterone has not been approved yet, or for patients who cannot afford it, ketoconazole is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that ketoconazole is a less potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abiraterone versus ketoconazole in docetaxel refractory mCRPC.

METHODS

Records from mCRPC patients treated with ketoconazole (international multicenter database, n = 162) were reviewed retrospectively. Twenty-six patients treated post docetaxel were individually matched by clinicopathologic factors to patients treated with abiraterone (national multicenter database, n = 140). We compared the PSA response, biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression.

RESULTS

The groups were matched by Gleason score, pre-treatment disease extent, ECOG PS, pre-treatment risk category (Keizman, Oncologist 2012). Furthermore, they were balanced regarding other known confounding risk factors. In the groups of abiraterone versus ketoconazole, PSA response was 46% versus 19% (OR 4.3, P = 0.04), median biochemical PFS 7 versus 2 months (HR 1.54, P = 0.02), median radiological PFS 8 versus 2.5 months (HR 1.8, P = 0.043), median OS 19 versus 11 months (HR 0.53, P = 0.79), and treatment interruption d/t severe adverse events 8% (n = 2) versus 31% (n = 8) (OR 0.6, P = 0.023).

CONCLUSIONS

In docetaxel refractory mCRPC, the outcome of abiraterone treatment may be superior to ketoconazole.

摘要

背景

阿比特龙是一种强效的CYP 17抑制剂，是多西他赛难治性转移性去势抵抗性前列腺癌（mCRPC）的标准治疗药物。然而，在阿比特龙尚未获批的国家，或对于无力承担该药费用的患者，酮康唑被用作替代的CYP 17抑制剂。尽管临床前数据表明酮康唑是一种效力较弱的CYP 17抑制剂，但比较这两种药物的临床数据有限。我们旨在比较阿比特龙与酮康唑在多西他赛难治性mCRPC中的临床疗效。

方法

回顾性分析接受酮康唑治疗的mCRPC患者的记录（国际多中心数据库，n = 162）。26例多西他赛后接受治疗的患者根据临床病理因素与接受阿比特龙治疗的患者（国家多中心数据库，n = 140）进行个体匹配。我们比较了两组之间的前列腺特异抗原（PSA）反应、生化和影像学无进展生存期（PFS）以及总生存期（OS）。PFS和OS通过Cox回归确定。

结果

两组在 Gleason评分、治疗前疾病范围、东部肿瘤协作组（ECOG）体能状态、治疗前风险类别（Keizman，《肿瘤学家》2012年）方面相匹配。此外，在其他已知的混杂风险因素方面两组也保持平衡。在阿比特龙组与酮康唑组中，PSA反应分别为46%和19%（比值比[OR] 4.3，P = 0.04），生化PFS中位数分别为7个月和2个月（风险比[HR] 1.54，P = 0.02），影像学PFS中位数分别为8个月和2.5个月（HR 1.8，P = 0.043），OS中位数分别为19个月和11个月（HR 0.53，P = 0.79），因严重不良事件导致的治疗中断率分别为8%（n = 2）和31%（n = 8）（OR 0.6，P = 0.023）。