短期雄激素剥夺治疗联合或不联合雄激素受体信号抑制剂后骨和矿物质稳态的变化 - 一项单中心、双盲、随机、安慰剂对照 2 期试验的亚研究。
Changes in bone and mineral homeostasis after short-term androgen deprivation therapy with or without androgen receptor signalling inhibitor - substudy of a single-centre, double blind, randomised, placebo-controlled phase 2 trial.
机构信息
Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
Department of Urology, University Hospitals Leuven, Leuven, Belgium; Urogenital, Abdominal and Plastic Surgery, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
出版信息
EBioMedicine. 2023 Nov;97:104817. doi: 10.1016/j.ebiom.2023.104817. Epub 2023 Oct 5.
BACKGROUND
Prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) have an increased fracture risk. Exploring biomarkers for early bone loss detection is of great interest.
METHODS
Pre-planned substudy of the ARNEO-trial (NCT03080116): a double blind, randomised, placebo-controlled phase 2 trial performed in high-risk PCa patients without bone metastases between March 2019 and April 2021. Patients were 1:1 randomised to treatment with gonadotropin-releasing hormone antagonist (degarelix) + androgen receptor signalling inhibitor (ARSI; apalutamide) versus degarelix + matching placebo for 12 weeks prior to prostatectomy. Before and following ADT, serum and 24-h urinary samples were collected. Primary endpoints were changes in calcium-phosphate homeostasis and bone biomarkers.
FINDINGS
Of the 89 randomised patients, 43 in the degarelix + apalutamide and 44 patients in the degarelix + placebo group were included in this substudy. Serum corrected calcium levels increased similarly in both treatment arms (mean difference +0.04 mmol/L, 95% confidence interval, 0.02; 0.06), and parathyroid hormone and 1,25-dihydroxyvitamin D levels decreased. Bone resorption markers increased, and stable calcium isotope ratios reflecting net bone mineral balance decreased in serum and urine similarly in both groups.
INTERPRETATION
This exploratory substudy suggests that 12 weeks of ADT in non-metastatic PCa patients results in early bone loss. Additional treatment with ARSI does not seem to more negatively influence bone loss in the early phase. Future studies should address if these early biomarkers are able to predict fracture risk, and can be implemented in clinical practice for follow-up of bone health in PCa patients under ADT.
FUNDING
Research Foundation Flanders; KU Leuven; University-Hospitals-Leuven.
背景
接受雄激素剥夺疗法 (ADT) 治疗的前列腺癌 (PCa) 患者骨折风险增加。探索用于早期骨丢失检测的生物标志物具有重要意义。
方法
ARNEO 试验的预先计划子研究 (NCT03080116)：这是一项在 2019 年 3 月至 2021 年 4 月期间患有无骨转移的高危 PCa 患者中进行的双盲、随机、安慰剂对照的 2 期试验。患者按 1:1 随机分配接受促性腺激素释放激素拮抗剂 (degarelix) + 雄激素受体信号抑制剂 (ARSI; apalutamide) 治疗或 degarelix + 匹配安慰剂治疗，共 12 周，随后进行前列腺切除术。在 ADT 之前和之后，采集血清和 24 小时尿液样本。主要终点是钙磷稳态和骨生物标志物的变化。
结果
在 89 名随机患者中，degarelix + apalutamide 组的 43 名患者和 degarelix + 安慰剂组的 44 名患者纳入了该子研究。两种治疗组的血清校正钙水平均相似地升高 (平均差值+0.04mmol/L，95%置信区间，0.02；0.06)，甲状旁腺激素和 1,25-二羟维生素 D 水平下降。骨吸收标志物增加，血清和尿液中的稳定钙同位素比值反映净骨矿物质平衡减少，两组均相似。
结论
这项探索性子研究表明，12 周的 ADT 治疗非转移性 PCa 患者会导致早期骨丢失。早期添加 ARSI 似乎不会对骨丢失产生更负面的影响。未来的研究应探讨这些早期生物标志物是否能够预测骨折风险，并可在临床实践中用于 ADT 下的 PCa 患者的骨健康随访。
资金
弗拉芒研究基金会；鲁汶天主教大学；鲁汶大学医院。
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