乳腺癌的内分泌治疗法研讨(ppt 34页)

AG 500mg
Anastrozole (Arimdex) vs
Megestrol Acetate in Advanced Breast Cancer
Phase III Trials
Survival Data Anastrozole / MA
60 50 40 30 20 10
0
Median time to death(months)
高选择性芳香化酶抑制剂
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) %
40%
P=0.03
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
1990‘s 新一代的芳香化酶抑制剂
30%
20%
10%
0% Femara 0.5mg
Femara 2.5mg
AG 500mg
Femara > AG
Median Duration of Clinical Benefit (months)
25
21个月
P=0.03
20 14个月
15
10
5
0 Femara 0.5mg Femara 2.5mg
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
Tamoxifen Adjuvant Therapy
Early Breast Cancer Triallists report on 55 trials in 37,000
women.
458 Tamoxifen
Letrozole
Tamoxifen
Progression
Survival Follow-up
Letrozole > Tamoxifen Response Rate (%)
50
P<0.001
45
40
35
P<0.001
30
25
20
Letrozole
Generation
Nonsteroidal Inhibitors
Steroidal Inactivators
First
Aminoglutethimide Testolactone
Second
Fadrozole
Formestane
Third
Anastrozole Letrozole
Exemestane
乳癌内分泌治疗药物
乙烯雌酚 MPA MA
雌激素 孕激素
TAM 抗雌激素
Droloxifene Toremifene
AG
Zoladex
芳香化酶抑制 (失活) 剂
兰他隆
Exemestane Arimidex
肾上腺皮质激 素类
Femara (Letrozole)
三苯氧胺 TAM （Tamoxifen,他莫昔芬）
Pregnenolone
Cortisol
Progesterone Aldosterone
Androstenedione
Testosterone
Aromatase Inactivators
and
Aromatase Inhibitors
Estrone
Estradiol
Anti-Aromatase Agents by Generation
P < 0.05
2 year survival rate (%)
Arimidex MA
Femara® ( letrozole ) vs
Tamoxifen
as First0-Li2ne5Therapy
Cross-Over Design
916 MBC
458 Letrozole
Progression
CrossOver
34
Recurrence Mortality
0
<50
50-59
>60
patient age (years)
8
Tamoxifen Adjuvant Therapy for Breast Cancer (IV)
no. of cases
Incidence in >20,000 patient follow-up years
Lancet 1998; 351: 1451
5
Tamoxifen Adjuvant Therapy for Breast Cancer (I)
Reductions in risk in ER+ patients
60 51
50
% reduction
40
30 22
20 11
10
34 17
28
Recurrence
Mortality
0 1 year
2 yrs
5 yrs of therapy
6
Tamoxifen Adjuvant Therapy for Breast Cancer (II)
Risk reduction by ER status (5yrs therapy)
50 50
40
37
30
20
10
6
28
21 Recurrence Mortality
% reduction
0
-3
-10
ER poor
ER unknown
ER +ve
7
Tamoxifen Adjuvant Therapy for Breast Cancer (III)
% reduction
Risk reduction by age, (ER+)
60
54
50
45
40
32
30
20
10
37 11
Peripheral tissues
Aromatase
Aromatase
= Estrogen = Androstenedione
Receptor
Tumor
Postmenopausal women
Anti-Aromatase Agents: Mechanism of Action
Cholesterol
157 160
wenku.baidu.com
140
120
100
91
80
60
40
20
0 contralat. b.c.
42 9
Endometrial cancer
Placebo Tamoxifen
9
The Role of Aromatase in Estrogen Biosynthesis and Tumor Growth
Adrenal gland