Dowsett M, Murray R M, Pitt P, Jeffcoate S L
Ann Clin Biochem. 1986 May;23 ( Pt 3):277-84. doi: 10.1177/000456328602300306.
Only 13% of postmenopausal advanced breast cancer patients responded to endocrine treatment with aminoglutethimide plus danazol whilst 33% responded to aminoglutethimide alone, despite a similar suppression of serum oestradiol levels in the two groups. The patients on aminoglutethimide and danazol showed a marked suppression of sex hormone binding-globulin binding capacity and a consequent rise in percent-free oestradiol. This led to the concentration of free oestradiol being less well suppressed than that of total oestradiol and in some patients free oestradiol concentrations were higher on treatment than before. Patients on aminoglutethimide alone showed no change in the binding of oestradiol and the percentage suppression of the free oestradiol concentration was similar to that of total oestradiol. The opposing effects of danazol and aminoglutethimide on the concentration of the free, biologically active fraction of oestradiol in the circulation may explain the poor therapeutic efficacy of this combination in breast cancer patients.
绝经后晚期乳腺癌患者中，仅13%对氨鲁米特加达那唑的内分泌治疗有反应，而单独使用氨鲁米特时33%有反应，尽管两组血清雌二醇水平受到相似程度的抑制。接受氨鲁米特和达那唑治疗的患者性激素结合球蛋白结合能力受到显著抑制，随之游离雌二醇百分比升高。这导致游离雌二醇浓度的抑制程度不如总雌二醇，而且在一些患者中，治疗期间游离雌二醇浓度高于治疗前。单独使用氨鲁米特的患者雌二醇结合情况无变化，游离雌二醇浓度的抑制百分比与总雌二醇相似。达那唑和氨鲁米特对循环中游离的、具有生物活性的雌二醇浓度产生的相反作用，可能解释了该联合用药对乳腺癌患者治疗效果不佳的原因。
