Paul R, Breul J
Department of Urology, Technische Universität Munich, Klinikum rechts der Isar, Germany.
Drug Saf. 2000 Nov;23(5):381-90. doi: 10.2165/00002018-200023050-00003.
The antiandrogen withdrawal syndrome is a well established phenomenon in prostate cancer. It is widely accepted that a subset of patients will benefit from the withdrawal of antiandrogen or steroidal hormone from hormonal therapy, exhibiting decreasing prostate-specific antigen (PSA) values and clinical improvement. The pathophysiology of antiandrogen withdrawal syndrome is not completely understood, although androgen receptor gene mutations seem to be the likely explanation. Currently, it is not possible to identify the subset of patients whose tumours will respond to antiandrogen or steroid withdrawal. Tumours that will respond may be classified as androgen-independent and hormone-sensitive tumours as opposed to androgen-independent and hormone-insensitive tumours that do not respond. Patients who respond to antiandrogen withdrawal experience approximately 6 months with improved quality of life; however, it is unknown if this translates into prolonged survival. At the very least, antiandrogen withdrawal offers a therapeutic modality that is not associated with adverse effects and improves quality of life even if only for a very limited time. Recent reports suggest that adding a secondary hormonal therapy such as amino- glutethimide, ketoconazole or steroidal hormones may enhance the response rate and prolong response time to the antiandrogen withdrawal syndrome. However, unless there is proof that this secondary hormonal manipulation prolongs survival, maintenance of quality of life is mandatory because of the possible adverse effects from these potent drugs. The fact that about 30% of patients will respond to antiandrogen or steroid withdrawal in hormone refractory prostate cancer must be taken into account in clinical trials of new cytotoxic agents which have been and will be conducted. Cessation of flutamide for at least 4 weeks and, in the case of bicalutamide, even 8 weeks, is mandatory before antiandrogen withdrawal syndrome can be excluded as the cause of decreasing PSA values. The antiandrogen withdrawal syndrome offers another piece of the puzzle of prostatic carcinoma, but at the same time it demonstrates how different advanced prostate cancer cells may react to therapeutic strategies and, therefore, hormone refractory prostate cancer remains a difficult challenge which must be solved in the future.
抗雄激素撤药综合征是前列腺癌中一种已被充分证实的现象。人们普遍认为，一部分患者会从激素治疗中停用抗雄激素或甾体激素中获益，表现为前列腺特异性抗原（PSA）值下降以及临床症状改善。尽管雄激素受体基因突变似乎是可能的解释，但抗雄激素撤药综合征的病理生理学尚未完全明确。目前，尚无法确定其肿瘤会对抗雄激素或甾体激素撤药产生反应的患者亚组。会产生反应的肿瘤可被归类为雄激素非依赖性且激素敏感型肿瘤，与之相对的是无反应的雄激素非依赖性且激素不敏感型肿瘤。对抗雄激素撤药有反应的患者生活质量改善约6个月；然而，这是否能转化为生存期延长尚不清楚。至少，抗雄激素撤药提供了一种无不良反应的治疗方式，即使仅在非常有限的时间内，也能改善生活质量。最近的报告表明，添加诸如氨鲁米特、酮康唑或甾体激素等二线激素治疗可能会提高抗雄激素撤药综合征的反应率并延长反应时间。然而，除非有证据表明这种二线激素干预能延长生存期，否则由于这些强效药物可能产生的不良反应，维持生活质量是必须的。在新的细胞毒性药物的临床试验中，必须考虑到约30%的激素难治性前列腺癌患者会对抗雄激素或甾体激素撤药产生反应这一事实。在排除抗雄激素撤药综合征作为PSA值下降原因之前，必须停用氟他胺至少4周，对于比卡鲁胺则需停用8周。抗雄激素撤药综合征为前列腺癌难题增添了新的内容，但同时也表明了不同的晚期前列腺癌细胞对治疗策略的反应可能不同，因此，激素难治性前列腺癌仍然是一个未来必须解决的艰巨挑战。
