课件：乳腺癌的内分泌治疗进展(复旦大学肿瘤医院).ppt

* When ‘Zoladex’ 3.6mg was administered chronically to female volunteers (n=7), its action on the pituitary gland resulted in a reduction in LH and oestradiol levels The reduction in LH production achieves suppression of oestradiol to levels comparable to those seen in postmenopausal women * ZEBRA = ‘Zoladex’ 3.6mg Early Breast Cancer Research Association The CMF regimen was: cyclophosphamide (500mg/m2, given i.v. on days 1 and 8, or 100mg/m2, given orally on days 1 to 14) methotrexate (40mg/m2, given i.v. on days 1 and 8) 5-fluorouracil (600mg/m2, given i.v. on days 1 and 8) Of those patients who received CMF, 83% had i.v. and 17% had oral cyclophosphamide * * Aromatization is, in fact, the terminal step in estrogen biosynthesis, and the drugs that affect aromatase are either inactivators of the enzyme or competitive inhibitors. It is this terminal step that is a target of specific therapies such as modern antiaromatase agents, also known as aromatase inhibitors. * In postmenopausal women, the adrenal gland secretes androgens that undergo aromatization predominantly in peripheral tissues such as muscle and adipose tissue. Another important site of conversion of androgens into estrogens has been recognized. Indeed tumor cells themselves are important reservoirs of aromatase activity. As newer hormonal therapies are being developed, it is therefore necessary that these agents be sufficiently selective and specific in targeting both the peripheral sites as well as the intratumoral sites of estrogen synthesis. * The development of these agents, in both the laboratory and the clinic, has represented a continuous evolution in the hormonal treatment of breast cancer. The first reports introduced the first-generation compounds, such as aminoglutethimide, which was associated with significant toxicity. Subsequently, second- and third-generation compounds have been developed. These compounds, including anastrozole, exemestane, and Femara? (letrozole) have shown exqui