The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Eur J Cancer. 2021 Feb;144:302-309. doi: 10.1016/j.ejca.2020.11.043. Epub 2020 Dec 29.
Cyclical, high-dose testosterone administration, termed bipolar androgen therapy (BAT), can induce clinical responses and restore sensitivity to androgen signalling inhibition in patients with previously treated castration-resistant prostate cancer (PCa) (CRPC). This trial evaluated whether BAT is a safe and effective first-line hormonal therapy for patients with CRPC.
In cohort C of this single-centre, open-label, phase II, multi-cohort trial (RE-sensitizing with Supraphysiologic Testosterone to Overcome REsistance study), 29 patients with CRPC received first-line hormonal therapy with 400 mg of testosterone cypionate intramuscularly every 28 days concurrent with a luteinising hormone-releasing hormone agonist/antagonist. The primary end-point of the study was the PSA response rate to BAT treatment.
After treatment with BAT, four of 29 patients (14%; 95% confidence interval [CI]: 4-32%) experienced a PSA response. The median radiographic progression-free survival to BAT was 8.5 months (95% CI: 6.9-15.1) for patients with metastatic CRPC. After progression on BAT, 17 of 18 patients (94%; 95% CI: 73-100%) achieved a PSA response and 15 of 18 patients (83%; 95% CI: 59-96) achieved a PSA response on abiraterone or enzalutamide. Twelve of 15 patients (80%; 95% CI: 52-96) with metastatic CRPC remain on abiraterone or enzalutamide with a median duration of follow-up of 11.2 months.
As first-line hormonal treatment for CRPC, BAT was well tolerated and resulted in prolonged disease stabilisation. After progression on BAT, patients had favourable responses to second-generation androgen receptor-targeted therapy.
ClinicalTrials.gov NCT02090114.
周期性、大剂量睾酮给药，称为双相雄激素治疗（BAT），可诱导先前接受过治疗的去势抵抗性前列腺癌（CRPC）患者的临床反应，并恢复对雄激素信号抑制的敏感性。本试验评估了 BAT 是否是 CRPC 患者安全有效的一线激素治疗方法。
在这项单中心、开放标签、多队列、二期试验（RE-sensitizing with Supraphysiologic Testosterone to Overcome REsistance 研究）的队列 C 中，29 例 CRPC 患者接受了一线激素治疗，即每 28 天肌内注射 400mg 睾酮环戊丙酸，同时使用黄体生成素释放激素激动剂/拮抗剂。研究的主要终点是 BAT 治疗的 PSA 反应率。
在接受 BAT 治疗后，29 例患者中有 4 例（14%；95%置信区间 [CI]：4-32%）出现 PSA 反应。转移性 CRPC 患者 BAT 的中位放射学无进展生存期为 8.5 个月（95% CI：6.9-15.1）。在 BAT 进展后，18 例患者中有 17 例（94%；95% CI：73-100%）出现 PSA 反应，18 例患者中有 15 例（83%；95% CI：59-96）出现阿比特龙或恩杂鲁胺的 PSA 反应。15 例转移性 CRPC 患者中有 12 例（80%；95% CI：52-96）继续使用阿比特龙或恩杂鲁胺，中位随访时间为 11.2 个月。
作为 CRPC 的一线激素治疗，BAT 耐受性良好，可延长疾病稳定期。在 BAT 进展后，患者对第二代雄激素受体靶向治疗有良好的反应。
ClinicalTrials.gov NCT02090114。
