Lank Center for Genitourinary Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
BJU Int. 2010 May;105(10):1392-6. doi: 10.1111/j.1464-410X.2009.08971.x. Epub 2009 Oct 23.
To assess the efficacy of the androgen-synthesis inhibitor ketoconazole as a secondary hormonal therapy in patients with castration-resistant prostate cancer (CRPC) previously treated with chemotherapy, as persistent androgens appear to play a role in the development and maintenance of CRPC.
We retrospectively identified 34 patients with CRPC who were treated with ketoconazole as a secondary hormonal therapy after paclitaxel- or docetaxel-based chemotherapy for CRPC. They were treated with ketoconazole 200-400 mg three times daily with or without hydrocortisone. Patients with previous use of ketoconazole were excluded. Half the patients had received estramustine as part of their chemotherapy regimen. The primary endpoint was the proportion of patients with a decline of > or =50% in their prostate-specific antigen (PSA) level. PSA progression was defined by the PSA Working Group 1 Criteria.
Eight of the 32 evaluable patients (25%) had a PSA decline of > or =50%. The median time to progression (TTP) was 3 months (95% confidence interval, 1.2-5.4). A history of previous response to taxane-based chemotherapy was not associated with the response to ketoconazole. However, previous use of oestrogens for CRPC was significantly associated with a shorter TTP on ketoconazole (1.5 vs 10.2 months; P = 0.03).
Ketoconazole has moderate activity as secondary hormonal therapy in patients with CRPC previously treated with taxane-based chemotherapy, although the TTP was short. Previous treatment with oestrogenic therapy is associated with a shorter TTP.
评估雄激素合成抑制剂酮康唑作为二线激素治疗在先前接受化疗的去势抵抗性前列腺癌（CRPC）患者中的疗效，因为持续的雄激素似乎在 CRPC 的发展和维持中起作用。
我们回顾性地确定了 34 例 CRPC 患者，他们在接受紫杉醇或多西他赛为基础的化疗治疗 CRPC 后，接受酮康唑作为二线激素治疗。他们每天三次服用酮康唑 200-400mg，同时或不服用氢可酮。先前使用过酮康唑的患者被排除在外。一半的患者在化疗方案中接受了雌莫司汀。主要终点是前列腺特异性抗原（PSA）水平下降>或=50%的患者比例。PSA 进展根据 PSA 工作组 1 标准定义。
32 例可评估患者中有 8 例（25%）PSA 下降>或=50%。中位无进展生存期（TTP）为 3 个月（95%置信区间，1.2-5.4）。先前对紫杉烷类化疗的反应与对酮康唑的反应无关。然而，先前使用雌激素治疗 CRPC 与酮康唑的 TTP 更短显著相关（1.5 与 10.2 个月；P=0.03）。
酮康唑作为二线激素治疗在先前接受紫杉烷类化疗的 CRPC 患者中具有中等活性，尽管 TTP 较短。先前使用雌激素治疗与 TTP 更短相关。
