■使用促黄体激素释放激素(LHRH)激动剂治疗前列腺癌的雄激素剥夺疗法(ADT)可以得到改善。
■为了评估安全性,潮热(HFs)的频率和严重程度,骨骼健康,大剂量雌四醇(HDE4)与ADT联用时的抗肿瘤作用。
■第二阶段,双盲,随机化,在需要ADT的晚期前列腺癌患者中进行了安慰剂对照研究(PCombi研究).
■接受LHRH激动剂治疗的患者随机分为2:1至40mgHDE4(n=41)或安慰剂(n=21)共治疗24周。
■共同终点是HF的频率/严重程度以及总睾酮和游离睾酮(T)水平。次要终点包括骨代谢评估(骨钙蛋白和I型胶原端肽[CTX1]),前列腺特异性抗原(PSA),和卵泡刺激素(FSH)。功效分析基于选定的符合方案(PP)群体。
■纳入研究的62名患者中,57例适用于PP分析(37例HDE4;20例安慰剂)。24周没有发生E4相关的严重心血管不良事件。每周HFs由13.5%的HDE4患者和60.0%的安慰剂患者报告(p<0.001)。每日HFs分别为5.9%和55%。骨转换参数随HDE4显著降低(p<0.0001)。总T和游离T下降较早(p<0.05),游离T被进一步抑制(p<0.05)。PSA抑制更严重和更早(p<0.005)。FSH水平抑制了98%对57%(p<0.0001)。雌激素副作用是乳头敏感性(34%)和男性乳房发育症(17%)。
■ADT合并治疗晚期前列腺癌患者的HDE4耐受性良好,24周时未观察到治疗相关的心血管不良事件.HFs和骨转换显著降低。抑制自由T,PSA,FSH更加快速和深刻,建议通过HDE4联合治疗加强疾病控制。需要更大和更持久的研究来确认此处报道的研究结果。
■在晚期前列腺癌患者中使用大剂量雌四醇进行雄激素剥夺治疗可减少潮热的发生,骨骼保护,和其他抗肿瘤的好处。乳头敏感和男性乳房发育可能作为副作用发生。
BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonists can be improved.
OBJECTIVE: To assess safety, the frequency and severity of hot flushes (HFs), bone health, and antitumor effects of high-dose
estetrol (HDE4) when combined with ADT.
METHODS: A phase II, double-blind, randomized, placebo-controlled study was conducted in advanced prostate cancer patients requiring ADT (the PCombi
study).
METHODS: Patients receiving LHRH agonist treatment were randomized 2:1 to 40 mg HDE4 (n = 41) or placebo (n = 21) cotreatment for 24 wk.
METHODS: Coprimary endpoints were frequency/severity of HFs and levels of total and free testosterone (T). Secondary endpoints included assessments of bone metabolism (osteocalcin and type I collagen telopeptide [CTX1]), prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH). Efficacy analysis was based on the selected per-protocol (PP) population.
CONCLUSIONS: Of 62 patients included in the
study, 57 were suitable for a PP analysis (37 HDE4; 20 placebo). No E4-related serious cardiovascular adverse events occurred at 24 wk. Weekly HFs were reported by 13.5% of patients with HDE4 and 60.0% with placebo (p < 0.001). Daily HFs occurred in 5.9% versus 55%. Bone turnover parameters decreased significantly with HDE4 (p < 0.0001). Total and free T decreased earlier (p < 0.05), and free T was suppressed further (p < 0.05). PSA suppression was more profound and earlier (p < 0.005). FSH levels were suppressed by 98% versus 57% (p < 0.0001). Estrogenic side effects were nipple sensitivity (34%) and gynecomastia (17%).
CONCLUSIONS: HDE4 cotreatment of ADT patients with advanced prostate cancer was well tolerated, and no treatment-related cardiovascular adverse events were observed at 24 wk. HFs and bone turnover were substantially reduced. Suppression of free T, PSA, and FSH was more rapid and profound, suggesting enhanced disease control by HDE4 cotreatment. Larger and longer-lasting studies are needed to confirm the results of the
study reported here.
RESULTS: Cotreatment of androgen deprivation therapy with high-dose
estetrol in advanced prostate cancer patients results in fewer occurrences of hot flushes, bone protection, and other antitumor benefits. Nipple sensitivity and gynecomastia may occur as side effects.