基线睾酮对度他雄胺和亮丙瑞林疗效的影响：来自前列腺癌患者为期 12 个月的比较性 III 期研究的进一步见解。
The effect of baseline testosterone on the efficacy of degarelix and leuprolide: further insights from a 12-month, comparative, phase III study in prostate cancer patients.
机构信息
Institute of Clinical Sciences, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
出版信息
Urology. 2012 Jul;80(1):174-80. doi: 10.1016/j.urology.2012.01.092.
OBJECTIVE
To investigate the effects of baseline testosterone on testosterone control and prostate-specific antigen (PSA) suppression using data from a phase III trial (CS21) comparing degarelix and leuprolide in prostate cancer.
METHODS
In CS21, patients with histologically confirmed prostate cancer (all stages) were randomized to degarelix 240 mg for 1 month followed by monthly maintenance doses of 80 or 160 mg, or leuprolide 7.5 mg/month. Patients receiving leuprolide could receive antiandrogens for flare protection. Treatment effects on testosterone and PSA reduction, testosterone surge, and microsurges were investigated in 3 baseline testosterone subgroups: <3.5, 3.5-5.0, and >5.0 ng/mL. Data are presented for the groups receiving degarelix 240/80 mg (the approved dose) and leuprolide 7.5 mg.
RESULTS
Higher baseline testosterone delayed castration with both treatments. However, castrate testosterone levels and PSA suppression occurred more rapidly with degarelix irrespective of baseline testosterone. With leuprolide, the magnitude of testosterone surge and microsurges increased with increasing baseline testosterone. There was no overall correlation between baseline testosterone and initial PSA decrease in either treatment group, although PSA suppression tended to be slowest with leuprolide and fastest with degarelix in the high baseline testosterone subgroup.
CONCLUSION
Patients with high baseline testosterone may have greater risk of tumor stimulation (clinical flare) and mini-flares during gonadotrophin-releasing hormone agonist treatment and so the need for flare protection with antiandrogens in these patients is obvious, especially in metastatic disease. Although higher baseline testosterone delays castration, castrate testosterone and PSA suppression occur more rapidly with degarelix, irrespective of baseline testosterone, without the need for flare protection.
目的
利用 III 期 CS21 试验（比较前列腺癌患者中戈舍瑞林和亮丙瑞林的疗效）的数据，探讨基线睾酮对睾酮控制和前列腺特异性抗原（PSA）抑制的影响。
方法
在 CS21 试验中，组织学确诊的前列腺癌（所有分期）患者被随机分配接受戈舍瑞林 240mg 治疗 1 个月，随后每月接受 80 或 160mg 的维持剂量，或亮丙瑞林 7.5mg/月。接受亮丙瑞林治疗的患者可以接受抗雄激素药物进行爆发保护。根据基线睾酮水平的 3 个亚组（<3.5ng/mL、3.5-5.0ng/mL 和>5.0ng/mL），研究治疗对睾酮和 PSA 降低、睾酮激增和微激增的影响。数据呈现接受戈舍瑞林 240/80mg（批准剂量）和亮丙瑞林 7.5mg 治疗的患者的结果。
结果
基线睾酮水平较高延迟了两种治疗方法的去势作用。然而，无论基线睾酮水平如何，戈舍瑞林治疗都能更快地实现去势睾酮水平和 PSA 抑制。亮丙瑞林治疗时，睾酮激增和微激增的幅度随基线睾酮水平的增加而增加。在两种治疗组中，基线睾酮与初始 PSA 降低之间没有总体相关性，尽管亮丙瑞林治疗组中基线睾酮较高的患者 PSA 抑制最慢，而戈舍瑞林治疗组中最快。
结论
基线睾酮水平较高的患者在促性腺激素释放激素激动剂治疗期间可能面临更大的肿瘤刺激（临床爆发）和微爆发风险，因此这些患者需要使用抗雄激素药物进行爆发保护，特别是在转移性疾病中。尽管基线睾酮水平较高会延迟去势作用，但戈舍瑞林治疗无论基线睾酮水平如何，都能更快地实现去势睾酮和 PSA 抑制，且无需爆发保护。
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