Anderson John, Abrahamsson Per-Anders, Crawford David, Miller Kurt, Tombal Bertrand
Department of Urology, The Royal Hallamshire Hospital, Sheffield, UK.
BJU Int. 2008 Jun;101(12):1497-501. doi: 10.1111/j.1464-410X.2008.07590.x. Epub 2008 Mar 11.
Gonadotrophin-releasing hormone (GnRH) agonists are currently the mainstay in the management of advanced prostate cancer. Used either as monotherapy or combined with antiandrogens, GnRH agonists suppress serum testosterone levels and thus slow the growth of the tumour cells that depend on testosterone for growth. GnRH agonists have largely replaced orchidectomy in the management of advanced prostate cancer, because patients are reluctant to undergo surgical castration. However, can we do better in androgen-deprivation therapy? There is some evidence to suggest that GnRH agonists do not achieve the level of testosterone suppression attained with orchidectomy, or as rapidly, factors which could be expected to affect overall survival. Together, these observations highlight the need to develop newer agents that can achieve rapid, profound and sustained testosterone suppression, equivalent to that with orchidectomy. Preliminary data for the GnRH blocker, degarelix, suggest that this new agent might overcome the shortcomings associated with GnRH agonists. Further clinical data are therefore awaited with much interest.
促性腺激素释放激素(GnRH)激动剂目前是晚期前列腺癌治疗的主要手段。GnRH激动剂可单独使用或与抗雄激素药物联合使用,抑制血清睾酮水平,从而减缓依赖睾酮生长的肿瘤细胞的生长。在晚期前列腺癌的治疗中,GnRH激动剂已在很大程度上取代了睾丸切除术,因为患者不愿接受手术去势。然而,在雄激素剥夺治疗中我们能否做得更好呢?有证据表明,GnRH激动剂无法达到睾丸切除术所实现的睾酮抑制水平,也无法像睾丸切除术那样迅速达到该水平,而这些因素可能会影响总生存期。综上所述,这些观察结果凸显了开发新型药物的必要性,这类药物能够实现与睾丸切除术相当的快速、深度且持续的睾酮抑制。GnRH拮抗剂地加瑞克的初步数据表明,这种新药可能会克服与GnRH激动剂相关的缺点。因此,人们满怀期待地等待进一步的临床数据。