Beardwell C G, Hindley A C, Wilkinson P M, St John J, Bu'lock D
Clin Endocrinol (Oxf). 1985 Oct;23(4):413-21. doi: 10.1111/j.1365-2265.1985.tb01099.x.
Postmenopausal women with metastatic breast cancer were treated with trilostane, initially 240 mg daily increasing after 3 days to 480 mg daily and after a further three days to 960 mg daily. After 3 days at this dose dexamethasone 1 mg daily was added and this combination was continued until disease progression occurred. Partial remission was seen in 26% and stabilization of previously progressive disease in a further 13% of the first twenty-three patients studied. During therapy with trilostane alone significant increases in DHEAS, androstenedione, 17-hydroxypregnenolone, progesterone, testosterone and oestradiol were seen. A significant fall in oestrone concentration occurred at the same time. After dexamethasone was added the elevated steroid concentrations fell back to the baseline while oestrone remained depressed below this and testosterone was also significantly lowered. No change was seen in cortisol or ACTH concentration while patients were on trilostane alone but cortisol levels were undetectable after dexamethasone was added though, in most patients, ACTH remained detectable. There was no change in the ratio of delta 5:delta 4 steroids at any stage of therapy but a highly significant increase in the androstenedione: oestrone ratio was seen. We conclude that in long-term use in vivo it is difficult to demonstrate that trilostane inhibits 3 beta-hydroxysteroid dehydrogenase but it may produce inhibition of aromatase.
患有转移性乳腺癌的绝经后女性接受曲洛司坦治疗，初始剂量为每日240毫克，3天后增至每日480毫克，再过3天后增至每日960毫克。在此剂量下服用3天后，加用每日1毫克地塞米松，该联合用药持续至疾病进展。在首批研究的23例患者中，26%出现部分缓解，另有13%先前进展的疾病病情稳定。在单独使用曲洛司坦治疗期间，硫酸脱氢表雄酮、雄烯二酮、17-羟孕烯醇酮、孕酮、睾酮和雌二醇显著升高。同时，雌酮浓度显著下降。加用地塞米松后，升高的类固醇浓度回落至基线水平，而雌酮仍低于基线水平，睾酮也显著降低。单独使用曲洛司坦时，皮质醇或促肾上腺皮质激素浓度无变化，但加用地塞米松后，多数患者皮质醇水平检测不到，不过促肾上腺皮质激素仍可检测到。治疗的任何阶段，δ5:δ4类固醇的比例均无变化，但雄烯二酮:雌酮的比例显著升高。我们得出结论，在体内长期使用时，很难证明曲洛司坦能抑制3β-羟类固醇脱氢酶，但它可能会抑制芳香化酶。
