Fornara P, Jocham D
Medizinische Universität zu Lübeck, Klinik und Poliklinik für Urologie, Germany.
Urol Int. 1996;56 Suppl 1:18-22. doi: 10.1159/000282864.
Androgen suppression, using gonadotrophin-releasing hormone analogues (leuprorelin), is being developed as an effective treatment of advanced prostate carcinoma. Treatment with leuprorelin acetate 1-month depot is already well established all over the world. In order to increase patients' acceptability of this treatment, by reducing frequency of administration, a 3-month depot formulation has been developed in Takeda's research laboratories. A single-shot pharmacokinetic study was conducted to confirm efficacy in terms of hormone suppression and safety of the 3-month depot formulation. Thereafter, a parallel-group, open-labelled, randomized trial was performed to compare clinical efficacy and safety profiles of the 1- and 3-month depot formulations. Patients with a histologically and/or cytologically confirmed advanced prostate carcinoma, without prior hormonal or surgical androgen deprivation, are included. According to 1:2 randomization, patients are treated with either the 1- or 3-month depot for 9 months. To prevent initial flare-up, a concomitant antiandrogen therapy might be administered within 2 weeks prior to first injection and continued for up to 3 weeks. The clinical efficacy of the formulations is assessed by both objective response, EORTC and NPCTG response criteria, and subjective response by using WHO performance status. In addition, the level of prostate-specific antigen is determined every 3 months. The efficacy of the two formulations is also evaluated by determination of serum testosterone, dihydrotestosterone, luteinizing hormone and follicle stimulating hormone. To date, 106 patients have been treated with the 3-month depot and 53 patients with the 1-month depot. Preliminary evaluation shows a satisfying level of testosterone suppression with both the 3- and 1-month depot formulations. Therapeutic equivalence was assumed. The 3-month depot is tolerated as well as the 1-month depot.
使用促性腺激素释放激素类似物（亮丙瑞林）进行雄激素抑制，正被开发为晚期前列腺癌的一种有效治疗方法。醋酸亮丙瑞林1个月长效注射剂的治疗方法在全球已得到广泛应用。为了通过减少给药频率来提高患者对这种治疗的接受度，武田制药的研究实验室已开发出一种3个月长效注射剂配方。进行了一项单次给药的药代动力学研究，以确认3个月长效注射剂配方在激素抑制方面的疗效和安全性。此后，进行了一项平行组、开放标签、随机试验，以比较1个月和3个月长效注射剂配方的临床疗效和安全性。纳入组织学和/或细胞学确诊的晚期前列腺癌患者，且之前未接受过激素或手术去势治疗。根据1:2随机分组，患者接受1个月或3个月长效注射剂治疗9个月。为防止初始病情加重，可在首次注射前2周内给予联合抗雄激素治疗，并持续3周。通过客观反应（欧洲癌症研究与治疗组织和美国国立前列腺癌项目反应标准）和使用世界卫生组织表现状态评估的主观反应来评估配方的临床疗效。此外，每3个月测定一次前列腺特异性抗原水平。还通过测定血清睾酮、双氢睾酮、促黄体生成素和促卵泡生成素来评估两种配方的疗效。迄今为止，106例患者接受了3个月长效注射剂治疗，53例患者接受了1个月长效注射剂治疗。初步评估显示，3个月和1个月长效注射剂配方在睾酮抑制方面均达到了令人满意的水平。假定具有治疗等效性。3个月长效注射剂的耐受性与1个月长效注射剂相同。
