Davies J H, Dowsett M, Jacobs S, Coombes R C, Hedley A, Shearer R J
Department of Urology, St Georges Hospital, Tooting, London, UK.
Br J Cancer. 1992 Jul;66(1):139-42. doi: 10.1038/bjc.1992.231.
We report the use of the steroidal aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA, CGP 32349), in the management of patients with advanced, hormone resistant, prostatic cancer. Eighteen of 25 patients (72%) showed a subjective response, mainly in the form of pain relief and increased performance. There were no objective improvements. A tumour flare occurred in 17/25 (68%). Detailed endocrine studies were performed during treatment. These showed that suppression of serum oestradiol levels occurred in 19/25 (76%) of patients during treatment with 4-OHA. Serum levels of androstenedione increased in 9/14 patients (64%). Concentration of serum testosterone and 5 alpha-dihydrotestosterone were elevated in 3/14 (21%) and 2/11 (18%) patients respectively. There appeared to be no correlation between response or tumour flare and changes in steroid levels during treatment with 4-OHA. The mechanism of action of 4-OHA in palliating patients with advanced prostatic cancer remains obscure. 4-OHA or its metabolites may be acting on metastatic bone metabolism via effects on oestrogen related osteoclastic and osteoblastic activity. Further investigation of the effects of aromatase inhibitors on prostatic biology, and bone metabolism in patients with metastatic prostate cancer, would appear worthwhile.
我们报告了甾体类芳香化酶抑制剂4-羟基雄烯二酮（4-OHA，CGP 32349）在晚期激素抵抗性前列腺癌患者治疗中的应用。25例患者中有18例（72%）出现主观反应，主要表现为疼痛缓解和身体机能改善。但未见客观改善。17/25（68%）的患者出现肿瘤 flare。治疗期间进行了详细的内分泌研究。结果显示，在使用4-OHA治疗期间，19/25（76%）的患者血清雌二醇水平受到抑制。9/14（64%）的患者血清雄烯二酮水平升高。3/14（21%）和2/11（18%）的患者血清睾酮和5α-双氢睾酮浓度分别升高。在使用4-OHA治疗期间，反应或肿瘤flare与类固醇水平变化之间似乎没有相关性。4-OHA缓解晚期前列腺癌患者症状的作用机制仍不清楚。4-OHA或其代谢产物可能通过影响雌激素相关的破骨细胞和成骨细胞活性作用于转移性骨代谢。进一步研究芳香化酶抑制剂对前列腺生物学以及转移性前列腺癌患者骨代谢的影响似乎是值得的。
