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[前列腺癌的雄激素剥夺治疗:临床证据与未来展望]

[Androgen-deprivation therapy in prostate cancer: clinical evidence and future perspectives].

作者信息

Pinto F, Calarco A, Totaro A, Sacco E, Volpe A, Racioppi M, D'Addessi A, Bassi P F

机构信息

Urologia, Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Roma.

出版信息

Urologia. 2010 Apr-May;77(2):71-83.

Abstract

Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.

摘要

雄激素参与前列腺癌的发生和发展,尽管其机制尚未完全明确。因此,雄激素剥夺疗法仍然是晚期和转移性疾病患者治疗的一个里程碑,并且在过去几年中,也与局部晚期肿瘤的放疗和手术联合使用。其他选择,如间歇性去势抑制,在临床益处和毒性方面似乎很有前景。然而,目前的治疗方法存在副作用,如睾酮激增导致临床症状突然加重、代谢综合征和激素抵抗,这些副作用会在数年的可变时间后出现。为了避免临床症状突然加重和睾酮微激增,已经开发了新型疗法,如促黄体激素释放激素(LH-RH)拮抗剂和长效缓释LH-RH类似物。新型雄激素合成抑制剂,如醋酸阿比特龙和MDV3100,最近已被发现并作为有前景的激素二线药物在去势抵抗性前列腺癌患者中进行测试。最后,应仔细监测并妥善治疗雄激素剥夺的长期副作用,如骨质疏松、肌肉减少性肥胖和心血管疾病。

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