Usami M, Kotake T, Matsuda M, Okajima E, Osafune M, Akaza H, Isurugi K, Niijima T, Aso Y, Araki T
Hinyokika Kiyo. 1988 Feb;34(2):369-82.
To investigate the clinical efficacy, safety and endocrinology of ICI 118630 (Zoladex) depot formulation at 3 different dose levels (0.9, 1.8 and 3.6 mg), 90 patients were randomized to receive either one of the 3 doses from April, 1985 to March, 1986 in 28 centers. The depot preparation was injected subcutaneously every 4 weeks 3 times (for up to 12 weeks). Clinical efficacy was evaluated in terms of tumor response and overall subjective response. In 70 patients eligible for tumor response evaluation, 14 out of 22 (63.6%) in the 0.9 mg group, 11 out of 23 (47.8%) in the 1.8 mg group, and 17 out of 25 (68.0%) in the 3.6 mg group showed clinical improvement, that is, either complete response or partial response. In 72 eligible patients for overall subjective response evaluation, clinical subjective improvement was observed in 75.0, 81.8 and 88.0% of the patients in the 3 groups, respectively. There was no significant difference between the groups. As for endocrinology, there were 75 eligible patients. Endocrinological effect was observed in 23 out of 25 (92.0%) in the 0.9 mg group, 100% in both 1.8 mg and 3.6 mg groups. There was no significant difference between the groups. Castration was achieved by week 3.5 +/- 1.7 of therapy on average and by week 2 in the earliest case. There was no significant difference in incidence of side effects between the 3 groups: 5 out of 26 (19.2%) in the 0.9 mg group, 8 out of 29 (27.6%) in the 1.8 mg group, and 2 out of 30 (6.7%) in the 3.6 mg group. Flares presented as an increase in bone pain in 2 and as ureteric obstruction in 2 all in the 1.8 mg group but none in the other 2 dose groups. These flares disappeared on further treatment with Zoladex. These patients showed a clinical-response. The blood level of Zoladex was dose dependent, reaching its peak at week 2 of therapy in all 3 dose groups. There was no evidence of accumulation. Since these results demonstrate that 3.6 mg produces medical castration earlier, it may well be considered as an optimal dose in men.
为研究醋酸亮丙瑞林微球（Zoladex）三种不同剂量水平（0.9、1.8和3.6毫克）的临床疗效、安全性及内分泌学情况，1985年4月至1986年3月期间，90例患者在28个中心被随机分配接受三种剂量中的一种。长效制剂每4周皮下注射1次，共注射3次（最长12周）。临床疗效根据肿瘤反应和总体主观反应进行评估。在70例符合肿瘤反应评估条件的患者中，0.9毫克组22例中有14例（63.6%）、1.8毫克组23例中有11例（47.8%）、3.6毫克组25例中有17例（68.0%）显示临床改善，即完全缓解或部分缓解。在72例符合总体主观反应评估条件的患者中，三组患者的临床主观改善率分别为75.0%、81.8%和88.0%。组间无显著差异。在内分泌学方面，有75例符合条件的患者。0.9毫克组25例中有23例（92.0%）观察到内分泌学效应，1.8毫克组和3.6毫克组均为100%。组间无显著差异。平均在治疗第3.5±1.7周实现去势，最早在第2周实现。三组副作用发生率无显著差异：0.9毫克组26例中有5例（19.2%）、1.8毫克组29例中有8例（27.6%）、3.6毫克组30例中有2例（6.7%）。1.8毫克组有2例出现骨痛加重、2例出现输尿管梗阻表现为“flare现象”，其他两个剂量组均无。这些“flare现象”在继续使用Zoladex治疗后消失。这些患者显示出临床反应。Zoladex的血药浓度呈剂量依赖性，所有三个剂量组在治疗第2周达到峰值。无蓄积证据。由于这些结果表明3.6毫克能更早实现药物去势，因此在男性中很可能被视为最佳剂量。
