Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Urology, Osaka International Cancer Institute, Osaka, Japan.
Jpn J Clin Oncol. 2024 May 7;54(5):584-591. doi: 10.1093/jjco/hyae004.
Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide.
The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients.
The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70.
In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.
抗雄激素治疗已被广泛用作去势抵抗性前列腺癌的一线治疗方法，它可能会影响后续针对雄激素受体轴的药物的治疗效果。我们进行了前瞻性观察 DELC（确定恩扎卢胺在接受比卡鲁胺联合雄激素阻断治疗后接受替代抗雄激素治疗的去势抵抗性前列腺癌患者中的长期安全性和疗效）研究，以评估恩扎卢胺在接受比卡鲁胺联合雄激素阻断治疗后接受替代抗雄激素治疗的去势抵抗性前列腺癌患者中的疗效。
DEL 研究纳入了 163 名在多家机构接受比卡鲁胺初始联合雄激素阻断治疗失败后接受氟他胺替代抗雄激素治疗的日本去势抵抗性前列腺癌患者，研究时间为 2016 年 1 月至 2019 年 3 月。主要终点为总生存期。所有患者均开始口服恩扎卢胺 160mg，每日 1 次。
前列腺特异性抗原下降 50%或更多的比例为 72.2%，中位总生存期为 42.05 个月。多变量分析显示，较高的预处理血清前列腺特异性抗原（≥11.3ng/mL；P=0.004）、神经元特异性烯醇化酶（P=0.014）和白细胞介素-6（≥2.15pg/mL；P=0.004）水平是总生存期的独立危险因素。最常见的临床相关不良事件是疲劳（30.0%）、便秘（19.6%）和食欲下降（17.8%）。70 岁以下患者的恩扎卢胺剂量未减少，但 70 岁以上患者的依从性降低。
在 DELC 研究中，恩扎卢胺的安全性与之前的报告相似。神经元特异性烯醇化酶和白细胞介素-6 的血清水平被认为是具有潜在临床应用价值的去势抵抗性前列腺癌的预后因素。
