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[使用长效促黄体生成素释放激素激动剂进行化学去势作为前列腺癌姑息治疗概念的临床、内分泌及实验研究]

[Chemical castration using a depot LHRH-agonist as a palliative therapy concept in prostatic carcinoma--clinical, endocrinological and experimental studies].

作者信息

Kuber W, Treu T, Kratzik C, Girsch E, Zeillinger R, Spona J

机构信息

Urologische Abteilung, Landeskrankenhaus Oberwart.

出版信息

Wien Klin Wochenschr. 1990 Nov 9;102(21):640-7.

PMID:2148044
Abstract

79 patients with locally advanced and/or metastatic prostate cancer were treated by means of a biodegradeable depot formulation of the luteinizing hormone releasing hormone analogue Goserelin (Zoladex). All patients received 3.6 mg depot Goserelin (Zoladex 3.6 mg implantate) subcutaneously into the anterior abdominal wall at 4 weekly intervals. The average time of observation was 24.2 months. The best objective response rate was found in 62%. Serum testosterone levels initially increased after the first depot injection and then decreased ultimately to castrate range (less than 0.6 ng/ml) between day 15 and day 27 (median 21) in the majority of patients. Castrate testosterone levels were still found 48 months after the start of treatment with depot Goserelin. 6 months after institution of treatment in 66.7% of cases evident signs of histological regression were found in the primary tumour tissue. Adenocarcinoma presented with a highly significantly better response pattern than anaplastic carcinoma. In animal experiments a single dose of 1 mg depot Goserelin was administered to adult male rats and the effect on serum testosterone levels and target organs (testes and ventral prostate) were investigated. Mean testosterone levels (mean = 0.31 ng/ml) decreased to castrate range (less than 0.3 ng/ml). 4 weeks after depot injection weight of the testes and prostate weight were significantly reduced. However 8 weeks after administration of 1 mg depot Goserelin there was no significant between the control group and the treated group. We conclude that the depot formulation of Goserelin (Zoladex) is effective, simple, practicable and safe in the treatment of advanced prostatic cancer. Current clinical studies are confirming the importance of reversible medical castration by LHRH agonists before radical prostatectomy.

摘要

79例局部晚期和/或转移性前列腺癌患者接受了促黄体生成素释放激素类似物戈舍瑞林(Zoladex)的可生物降解长效制剂治疗。所有患者均接受3.6mg长效戈舍瑞林(Zoladex 3.6mg植入剂),于前腹壁皮下注射,每4周1次。平均观察时间为24.2个月。最佳客观缓解率为62%。大多数患者首次注射长效制剂后血清睾酮水平最初升高,随后最终降至去势水平(低于0.6ng/ml),时间在第15天至第27天(中位数为21天)之间。开始使用长效戈舍瑞林治疗48个月后仍可检测到去势水平的睾酮。治疗6个月后,66.7%的病例在原发肿瘤组织中发现明显的组织学消退迹象。腺癌的反应模式明显优于间变性癌。在动物实验中,给成年雄性大鼠单次注射1mg长效戈舍瑞林,并研究其对血清睾酮水平和靶器官(睾丸和前列腺腹侧)的影响。平均睾酮水平(平均值=0.31ng/ml)降至去势水平(低于0.3ng/ml)。注射长效制剂4周后,睾丸重量和前列腺重量显著降低。然而,在注射1mg长效戈舍瑞林8周后,对照组和治疗组之间没有显著差异。我们得出结论,戈舍瑞林(Zoladex)长效制剂在晚期前列腺癌治疗中有效、简单、可行且安全。目前的临床研究正在证实,在根治性前列腺切除术之前,通过促性腺激素释放激素激动剂进行可逆性药物去势的重要性。

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