Murphy G P, Greco J M, Chin J L, Huben R P, Scott M, deHaan H A
Urology. 1987 Feb;29(2):185-90. doi: 10.1016/0090-4295(87)90150-6.
Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation.
27例前列腺转移性腺癌患者接受了新型促黄体生成激素释放激素类似物Zoladex（ICI 118,630）治疗，疗程长达98周。最初，治疗被随机分为两组，一组患者每天皮下自行注射250微克Zoladex，另一组患者每天皮下自行注射500微克Zoladex，最少治疗12周，之后使用Zoladex 3.6毫克的长效、每月一次的皮下注射剂型。头两天血清促性腺激素和睾酮急剧上升，随后三周激素水平下降。每天注射500微克达到去势的中位时间为22天，而每天注射250微克为43天（p = 0.06）。转换为长效剂型期间未发生明显的内分泌变化，整个研究期间血清睾酮一直被抑制在95%。三个月后，Zoladex的中位每日血清浓度在0.47至0.53纳克/毫升之间，三种剂型之间无显著差异。未发现血清Zoladex浓度、内分泌参数和肿瘤反应率之间存在特定相关性。最初的潮热和性欲减退是唯一常见的主诉。Zoladex耐受性良好，没有副作用需要调整剂量或退出研究。长达一年的肿瘤反应率似乎与传统内分泌疗法相当。推荐使用这种每月一次的长效剂型类似物进行进一步的临床评估。
