课件：乳腺癌的内分泌治疗进展.ppt

* AstraZeneca has developed a biodegradable, sustained-release depot formulation of goserelin (‘Zoladex’ 3.6mg), which releases the drug continuously over a period of at least 28 days, following subcutaneous administration * Following initial administration of ‘Zoladex’ 3.6mg depot, all the LHRH receptors on the surface of the pituitary cell become occupied by goserelin (Figure A) This results in a transient increase in serum LH, but the occupied LHRH receptors form clusters and gradually disappear into the cell, leading to a profound suppression of LH and, subsequently, of oestradiol New receptors are constantly resynthesised but, once again, they become occupied by the goserelin, which is continually released from the ‘Zoladex’ 3.6mg depot Hence, on chronic administration of ‘Zoladex’ 3.6mg, the continuous presence of goserelin prevents a sufficiently large amount of LHRH receptors from being stimulated by the pituitary gland to produce a normal amount of LH and, therefore, the production of oestrogens is suppressed to postmenopausal levels, essentially producing a ‘medical castration’ (Figure B) Reference Furr BJA. Hormone Res 1989; 32 (Suppl1): 86–92. * 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 * Diagrammatic representation of the hypothalamic-pituitary-ovarian axis. The triangle represents the hypothalamus; the ovoid, the pituitary; and t