Barts Cancer Institute, Saint Bartholomew's Hospital, London, UK.
Department of Medical Oncology, Charing Cross Hospital, Imperial College NHS Trust, London, UK.
Clin Genitourin Cancer. 2020 Jun;18(3):e217-e223. doi: 10.1016/j.clgc.2019.09.019. Epub 2019 Oct 10.
Androgen-deprivation therapy is the mainstay of treatment for metastatic prostate cancer. Corticosteroids and estrogens are also useful agents in castration-resistant prostate cancer (CRPC). However, oral estrogens are associated with thromboembolic events, which limits their use, and transdermal estrogens may offer a safer alternative. This study was carried out to determine the safety and effectiveness of transdermal estrogens in CRPC.
Forty-one patients with CRPC and steroid-resistant prostate cancer were eligible for this dose-escalation study of transdermal estradiol. A starting dose of 50 mcg/24 hours was applied and increased if prostate-specific antigen (PSA) rose > 5 ng/mL in steps to 300 mcg/24 hours. The primary endpoint was PSA response, and secondary outcomes included incidence of thromboembolic events and progression-free survival. Patients who progressed were offered diethylstilbestrol.
Five (13%) of 40 patients had > 50% PSA reduction for at least 1 month at any transdermal estradiol dose. No venous-thromboembolic events were observed, and responses plateaued at 200 mcg/24 hours. A correlation between PSA response and rising sex hormone binding globulin was seen. Fifty percent of patients subsequently responded to low-dose diethylstilbestrol.
Transdermal estradiol appears to be a low toxicity treatment option to control CRPC after failure of steroid therapy. Modulation of sex hormone binding globulin by transdermal estradiol may be one mechanism of action of estrogens on CRPC. Oral estrogens remain effective after the use of transdermal estradiol.
去势治疗是转移性前列腺癌的主要治疗方法。皮质类固醇和雌激素也是去势抵抗性前列腺癌（CRPC）的有效药物。然而，口服雌激素会引起血栓栓塞事件，限制了其应用，而透皮雌激素可能提供更安全的替代方案。本研究旨在确定透皮雌激素治疗 CRPC 的安全性和有效性。
41 例 CRPC 和类固醇难治性前列腺癌患者符合本研究的透皮雌二醇剂量递增研究条件。起始剂量为 50mcg/24 小时，如果前列腺特异性抗原（PSA）升高>5ng/ml，则以 50mcg/24 小时的剂量递增，最高剂量为 300mcg/24 小时。主要终点是 PSA 反应，次要终点包括血栓栓塞事件的发生率和无进展生存期。进展的患者给予己烯雌酚。
40 例患者中有 5 例（13%）在任何透皮雌二醇剂量下 PSA 至少降低 50%，持续 1 个月以上。未观察到静脉血栓栓塞事件，在 200mcg/24 小时时反应趋于平稳。PSA 反应与性激素结合球蛋白升高呈正相关。50%的患者随后对低剂量己烯雌酚有反应。
在类固醇治疗失败后，透皮雌二醇似乎是一种低毒性的治疗选择，可以控制 CRPC。透皮雌二醇对性激素结合球蛋白的调节可能是雌激素对 CRPC 作用的一种机制。在使用透皮雌二醇后，口服雌激素仍然有效。
