Weckermann Dorothea, Harzmann Rolf
Department of Urology, Klinikum Augsburg, Stenglinstr. 2, 86156, Germany.
Eur Urol. 2004 Sep;46(3):279-83; discussion 283-4. doi: 10.1016/j.eururo.2004.05.006.
GnRH agonists have a proven and well-established role in the management of prostate cancer. Further adaptations of the amino-acid sequence led to the development of antagonists with potential therapeutic uses, including a possible role in prostate cancer patients. Treatment of prostate cancer with GnRH agonists results in an initial flare of symptoms that may be prevented by co-administration of a steroidal or non-steroidal antiandrogen. However, this can be associated with additional adverse effects. Clinical studies have shown that GnRH antagonists produce a rapid decline in testosterone but without the disease flare. However these short-term effects have yet to be proven to lead to long-term survival benefits. There have been some reports that antagonists may be associated with adverse effects due to histamine release leading to severe allergic reactions. GnRH agonists are currently available in a range of depot formulations, allowing treatment to be tailored to the patient's needs. At present, the antagonists are only available as on-month depot formulations, which may limit their clinical use. Abarelix should be given intramuscularly. It is the first GnRH antagonist which is approved by the FDA for patients with advanced prostate cancer who should be treated under a risk management program. In Europe, abarelix has not been registered yet.
促性腺激素释放激素(GnRH)激动剂在前列腺癌的治疗中已被证实具有明确且成熟的作用。氨基酸序列的进一步改造导致了具有潜在治疗用途的拮抗剂的开发,包括在前列腺癌患者中可能发挥的作用。用GnRH激动剂治疗前列腺癌会导致症状最初出现加剧,这可通过同时给予甾体或非甾体抗雄激素药物来预防。然而,这可能会伴有额外的不良反应。临床研究表明,GnRH拮抗剂可使睾酮迅速下降,但不会出现疾病加剧。然而,这些短期效果尚未被证实能带来长期生存益处。有一些报道称,拮抗剂可能因组胺释放导致严重过敏反应而与不良反应相关。GnRH激动剂目前有多种长效注射制剂可供选择,可根据患者需求进行治疗定制。目前,拮抗剂仅有一种每月一次的长效注射制剂,这可能会限制其临床应用。阿巴瑞克应通过肌肉注射给药。它是首个被美国食品药品监督管理局(FDA)批准用于晚期前列腺癌患者的GnRH拮抗剂,这些患者应在风险管理计划下接受治疗。在欧洲,阿巴瑞克尚未注册。