OBJECTIVE RESPONSES TO KETOCONAZOLE THERAPY IN PATIENTS WITH RELAPSED PROGRESSIVE PROSTATIC-CANCER
OBJECTIVE RESPONSES TO KETOCONAZOLE THERAPY IN PATIENTS WITH RELAPSED PROGRESSIVE PROSTATIC-CANCER
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DOI：
10.1111/j.1464-410x.1986.tb05426.x
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发表时间：
1986-02-01
期刊：
影响因子：
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通讯作者：
BLOOM, SR
中科院分区：
文献类型：
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作者：
WILLIAMS, G;KERLE, DJ;BLOOM, SR
在20例晚期复发前列腺癌患者中，研究了肾上腺雄激素对所谓激素无反应前列腺癌的维持和进展的贡献。睾丸雄激素的作用已被既往的睾丸切除术或同时的LHRH类似治疗所否定。酮康唑是一种抑制肾上腺和睾丸雄激素生成的抗真菌剂，剂量为400mg，每小时8次，可达到抑制肾上腺雄激素的最佳效果。平均血清雄烯二酮浓度从8.01 +-下降。从0.84 nMol/l到1.55。0.25 nMol/l, P < 0.001，血清睾酮从1.25。从0.14 nMol/l到0.36。0.06 nMol/l, P < 0.01。然而，服用400毫克和200毫克的患者之间没有显著差异。雄激素抑制导致6个客观临床反应和10个主观临床反应。目前，酮康唑联合睾丸切除术或LHRH类似物可实现睾丸和肾上腺雄激素的消融，但副作用的高发生率可能使其无法用于所有前列腺癌患者。本研究结果支持“全雄激素消融”作为晚期前列腺癌的主要治疗方法，作为提高这种常见恶性肿瘤生存率的可能手段。
The contribution of adrenal androgens to the maintenance and progression of so-called hormone-unresponsive prostatic carcinoma was studied in 20 patients with advanced relapsed disease. The role played by testicular androgens had been negated by prior orchiectomy or concurrent LHRH analogue therapy. Ketoconazole, an antifungal agent which inhibits adrenal and testicular androgenesis, administered in a dose of 400 mg 8-hourly, resulted in optimal suppression of adrenal androgens. The mean serum androstenedione concentration fell from 8.01 .+-. 0.84 nMol/l to 1.55 .+-. 0.25 nMol/l, P < 0.001, and serum testosterone from 1.25 .+-. 0.14 nMol/l to 0.36 .+-. 0.06 nMol/l, P < 0.01, after 6 months treatment. There was, however, no significant differnce between patients receiving 400 and those receiving 200 mg. Androgen suppression resulted in six objective and ten subjective clinical responses. Ablation of both testicular and adrenal androgens can now be achieved using ketoconazole in combination with orchiectomy or LHRH analogues, but the high incidence of side effects may preclude its use in all patients with prostatic cancer. The results of this study support the concept of "total androgen ablation" as primary therapy in advanced prostatic cancer as a possible means of improving survival in this common malignancy.