乳腺癌辅助内分泌治疗相关试验.ppt
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1、乳腺癌的内分泌治疗,乳癌内分泌治疗历史,1896年 卵巢切除术治疗复发转移乳癌 1922年 放疗卵巢去势 1939年 雄性激素 1944年 人工合成雌激素 1951年 孕激素 1953年 肾上腺切除和下丘脑切除 1973年 三苯氧胺 1981年 芳香化酶抑制剂 1990s 新一代的芳香化酶抑制剂,乳癌内分泌治疗药物,三苯氧胺 TAM (Tamoxifen,他莫昔芬),目前最常用的非甾体类抗雌激素药 复发转移乳癌的解救治疗 乳癌术后预防复发转移的辅助治疗 高危健康妇女预防乳癌,TrialsFE,5,Tamoxifen Adjuvant Therapy,Early Breast Cancer Tr
2、iallists report on 55 trials in 37,000 women.,Lancet 1998; 351: 1451,TrialsFE,6,Tamoxifen Adjuvant Therapy for Breast Cancer (I),TrialsFE,7,Tamoxifen Adjuvant Therapy for Breast Cancer (II),TrialsFE,8,Tamoxifen Adjuvant Therapy for Breast Cancer (III),TrialsFE,9,Tamoxifen Adjuvant Therapy for Breast
3、 Cancer (IV),Aromatase,Aromatase,The Role of Aromatase in Estrogen Biosynthesis and Tumor Growth,Adrenal gland,Peripheral tissues,Postmenopausal women,Tumor,= Estrogen = Androstenedione,Receptor,Estrone,Estradiol,Testosterone,Aromatase Inactivators and Aromatase Inhibitors,Androstenedione,Anti-Aroma
4、tase Agents: Mechanism of Action,Cholesterol,Cortisol,Progesterone,Aldosterone,Pregnenolone,Generation First Second Third,Anti-Aromatase Agents by Generation,Nonsteroidal Inhibitors Aminoglutethimide Fadrozole Anastrozole Letrozole,Steroidal Inactivators Testolactone Formestane Exemestane,高选择性芳香化酶抑制
5、剂,选择性抑制芳香化酶 作用强度更强 不良反应更轻,Femara (Letrozole) vs Aminoglutethimide (AG),Phase III Trial,Femara AG Clinical Benefit (CR+PR+SD=6 个月) %,P=0.03,Femara AG Median Duration of Clinical Benefit (months),P=0.03,14个月,21个月,AdexProdFE,Anastrozole (Arimdex) vs Megestrol Acetate in Advanced Breast Cancer Phase III
6、 Trials,Survival Data Anastrozole / MA,Median time to death(months),2 year survival rate (%),P 0.05,Femara ( letrozole ) vs Tamoxifen as First-Line Therapy,0 2 5,Cross-Over Design 916 MBC,458 Letrozole,458 Tamoxifen,Progression,Cross-Over,Progression,Survival Follow-up,Letrozole,Tamoxifen,Letrozole
7、Tamoxifen Response Rate (%),P0.001,P0.001,TTP: Kaplan-Meier Curve,Femara ( letrozole ) vs Tamoxifen as Pre-Operative Therapy,0 2 4,Design,Double-blind, double-dummy, randomized, parallel group, multicenter (55 centers in 16 countries), phase IIb/III trial,Femara (letrozole) 2.5 mg o.d.,Tamoxifen 20
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- 乳腺癌 辅助 内分泌 治疗 相关 试验
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