Liu Ying, Yang Tao, Xu Chengdang, Chen Xi, Chi Yongnan, Zhou Weidong, Le Wei, Bian Cuidong, Li Zhenfei, Huang Shengsong, Wu Denglong
Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
Transl Androl Urol. 2022 Aug;11(8):1169-1176. doi: 10.21037/tau-22-507.
The steroidal metabolism of abiraterone has been proposed to be involved in abiraterone resistance and limited approaches are available for abiraterone-resistant patients. Dutasteride regulates abiraterone metabolism in patients and might enhance the clinical efficacy of abiraterone. However, the function of dutasteride to overcome abiraterone resistance has not been investigated in clinic. Here we investigated the clinical efficacy and limitations of dutasteride in patients with abiraterone-resistant prostate cancer.
Abiraterone-resistant patients with metastatic castration-resistant prostate cancer (mCRPC) were enrolled in this single-arm, open-label study, patients were treated with dutasteride (0.5 mg/day), abiraterone (1,000 mg/day), and prednisone (5 mg twice daily), prostate-specific antigen (PSA) was tested monthly. The primary objective was PSA response, and the secondary objectives were to assess symptom relief and safety. Kaplan-Meier analysis was used to assess the PSA progression free survival (PSA-PFS) of patients.
Twenty-two patients (median age: 75 years) were enrolled, and 19 patients completed the treatment. After a median treatment of 4.0 months, 7 (37%) patients showed a slight PSA reduction (-2% to -32%), and the median PSA-PFS was 2.0 months (1-7 months). No significant improvement was observed in Eastern Cooperative Oncology Group (ECOG) performance status. Bone pain was relieved in 6 patients after 1 month of treatment, but the improvement was not significant. No grade 3 or grade 4 adverse events were observed.
The combination of dutasteride and abiraterone showed a mild effect in patients with abiraterone-resistant. The small sample size was the limitation of this study.
阿比特龙的甾体代谢被认为与阿比特龙耐药有关，而针对阿比特龙耐药患者的治疗方法有限。度他雄胺可调节患者体内阿比特龙的代谢，可能增强阿比特龙的临床疗效。然而，度他雄胺克服阿比特龙耐药的作用尚未在临床上进行研究。在此，我们研究了度他雄胺在阿比特龙耐药前列腺癌患者中的临床疗效及局限性。
转移性去势抵抗性前列腺癌（mCRPC）的阿比特龙耐药患者被纳入这项单臂、开放标签研究，患者接受度他雄胺（0.5毫克/天）、阿比特龙（1000毫克/天）和泼尼松（5毫克，每日两次）治疗，每月检测前列腺特异性抗原（PSA）。主要目标是PSA反应，次要目标是评估症状缓解情况和安全性。采用Kaplan-Meier分析评估患者的PSA无进展生存期（PSA-PFS）。
共纳入22例患者（中位年龄：75岁），19例患者完成治疗。中位治疗4.0个月后，7例（37%）患者的PSA略有下降（-2%至-32%），中位PSA-PFS为2.0个月（1-7个月）。东部肿瘤协作组（ECOG）体能状态未观察到显著改善。1个月治疗后6例患者的骨痛得到缓解，但改善不显著。未观察到3级或4级不良事件。
度他雄胺与阿比特龙联合应用对阿比特龙耐药患者显示出轻微疗效。本研究的局限性在于样本量较小。
