Department of Biomedical and Clinical Sciences, Linköping University, Linköping, 581 83, Sweden.
Department of Oncology, Ryhov County Hospital, Jönköping, 551 85, Sweden.
BMC Cancer. 2023 Apr 4;23(1):309. doi: 10.1186/s12885-023-10780-y.
Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge and evidence for late-line treatments in real-life is limited. The present study investigates the efficacy and safety of an oral metronomic chemo-hormonal regimen including cyclophosphamide, etoposide, estramustine, ketoconazole and prednisolone (KEES) administered in a consecutive biweekly schedule.
A retrospective cohort study in two Swedish regions was conducted. Overall (OS) and progression-free survival (PFS), biochemical response rate (bRR) and toxicities were analyzed.
One hundred and twenty-three patients treated with KEES after initial treatment with at least a taxane or an androgen-receptor targeting agents (ARTA) were identified. Of those, 95 (77%) had received both agents and were the primary analysis population. Median (95% CI) OS and PFS in the pre-treated population were 12.3 (10.1-15.0) and 4.4 (3.8-5.5) months, respectively. Biochemical response, defined as ≥ 50% prostate-specific antigen (PSA) reduction, occurred in 26 patients (29%), and any PSA reduction in 59 (65%). PFS was independent of prior treatments used, and KEES seemed to be effective in late treatment lines. The bRR was higher compared to historical data of metronomic treatments in docetaxel and ARTA pre-treated populations. In multivariable analyses, performance status (PS) ≥ 2 and increasing alkaline phosphatase (ALP) predicted for worse OS. Nausea, fatigue, thromboembolic events and bone marrow suppression were the predominant toxicities.
KEES demonstrated meaningful efficacy in heavily pre-treated CRPC patients, especially those with PS 0-1 and lower baseline ALP, and had an acceptable toxicity profile.
转移性去势抵抗性前列腺癌（mCRPC）仍然是一个治疗挑战，实际应用中晚期治疗的证据有限。本研究调查了包括环磷酰胺、依托泊苷、雌莫司汀、酮康唑和泼尼松龙（KEES）在内的口服节拍化疗-激素方案的疗效和安全性，该方案按连续双周方案给药。
在瑞典的两个地区进行了一项回顾性队列研究。分析了总生存期（OS）和无进展生存期（PFS）、生化缓解率（bRR）和毒性。
确定了 123 例在初始治疗中至少接受过紫杉烷或雄激素受体靶向药物（ARTA）治疗后接受 KEES 治疗的患者。其中，95 例（77%）接受了两种药物治疗，为主要分析人群。预处理人群的中位（95%CI）OS 和 PFS 分别为 12.3（10.1-15.0）和 4.4（3.8-5.5）个月。生化缓解定义为前列腺特异性抗原（PSA）降低≥50%，有 26 例（29%）患者发生，59 例（65%）患者有任何 PSA 降低。PFS与既往使用的治疗无关，KEES 在晚期治疗线中似乎有效。与 docetaxel 和 ARTA 预处理人群的节拍治疗的历史数据相比，bRR 更高。在多变量分析中，表现状态（PS）≥2 和碱性磷酸酶（ALP）升高预示 OS 较差。恶心、疲劳、血栓栓塞事件和骨髓抑制是主要毒性。
KEES 在接受过大量预处理的 CRPC 患者中显示出有意义的疗效，尤其是 PS 0-1 和基线 ALP 较低的患者，且具有可接受的毒性特征。
