Schulze H, Senge T
Department of Urology, University of Bochum, Herne, Federal Republic of Germany.
J Urol. 1990 Oct;144(4):934-41. doi: 10.1016/s0022-5347(17)39625-8.
The long-term effect of the luteinizing hormone-releasing hormone analogue-induced initial testosterone surge in the treatment of patients with metastatic carcinoma of the prostate still is unknown. However, acute worsening of the disease has been reported in up to 10% of the patients. To prevent such tumor flare we investigated the endocrinological effects of different types of antiandrogens administered in addition to a luteinizing hormone-releasing hormone analogue. Patients with newly diagnosed metastatic prostate cancer were pre-treated with either the steroidal antiandrogen cyproterone acetate (6) or the nonsteroidal antiandrogen flutamide (5) for 1 week before the initial injection of the depot luteinizing hormone-releasing hormone analogue Zoladex. In another 5 patients flutamide was first given 24 hours before Zoladex therapy was started. Luteinizing hormone, testosterone and prostatic acid phosphatase during month 1 of luteinizing hormone-releasing hormone analogue therapy were compared to data obtained in 5 patients treated by Zoladex alone. Only pre-treatment with cyproterone acetate was capable of preventing the Zoladex-induced testosterone surge. However, both pre-treatment regimens with either cyproterone acetate or flutamide for 1 week prevented an initial increase in prostatic acid phosphatase beyond pre-treatment levels in all patients. In contrast, in 4 of 5 patients treated with Zoladex alone and in 2 of 5 pre-treated with flutamide for 1 day an initial increase in prostatic acid phosphatase beyond the pre-treatment values was seen. Our data indicate that pre-treatment with flutamide for only 1 day may not be sufficient to prevent a luteinizing hormone-releasing hormone analogue-induced tumor flare in all cases.
促黄体生成激素释放激素类似物诱导的初始睾酮激增在前列腺癌转移患者治疗中的长期效果尚不清楚。然而，据报道高达10%的患者病情会急性恶化。为预防这种肿瘤发作，我们研究了除促黄体生成激素释放激素类似物外给予不同类型抗雄激素药物的内分泌学效应。新诊断的前列腺癌转移患者在首次注射长效促黄体生成激素释放激素类似物诺雷德前，先用甾体类抗雄激素醋酸环丙孕酮（6例）或非甾体类抗雄激素氟他胺（5例）预处理1周。另外5例患者在开始诺雷德治疗前24小时先给予氟他胺。将促黄体生成激素释放激素类似物治疗第1个月期间的促黄体生成激素、睾酮和前列腺酸性磷酸酶水平与5例仅接受诺雷德治疗的患者的数据进行比较。只有醋酸环丙孕酮预处理能够预防诺雷德诱导的睾酮激增。然而，醋酸环丙孕酮或氟他胺预处理1周的两种方案均能防止所有患者前列腺酸性磷酸酶初始水平升高超过预处理水平。相比之下，在5例仅接受诺雷德治疗的患者中有4例，以及在5例用氟他胺预处理1天的患者中有2例，观察到前列腺酸性磷酸酶初始水平升高超过预处理值。我们的数据表明，仅用氟他胺预处理1天可能不足以在所有情况下预防促黄体生成激素释放激素类似物诱导的肿瘤发作。
