乳腺癌的内科治疗

CALGB 9344 trial (3170): AC→T 方案与AC方案的随
机对照研究：FDA 99年10月批准在LN+ 乳腺癌辅助化疗 Regimen
Group 1 AC×4 (ADR 60/75/90mg/m2)
Group 2 AC×4 → Paclitaxel 175mg/m2 × 4 (q3w) ER(+) TAM for 5yrs
Dose Density
A randomized trial
of alternating versus sequential therapy using single-agent doxorubicin and CMF that was conducted in Milan.

Over 400 women with >= 4 LN+ Regimen: 4 cycles of doxorubicin and 8 of CMF less dose-dense arm: 2 cycles of CMF followed by 1 cycle of doxorubicin (CCACCACCACCA), more dose-dense arm: all 4 cycles of doxorubicin followed
不良反应： CHF 2%
血栓 1-2%
MDS/AL 0.8%
内膜癌 1% 37th ASCO
Arm 2 TAM+CAF (1116)
Leabharlann Baidu
76%
84%
乳腺癌辅助化疗的临床研究
高剂量化疗和干细胞支持治疗—随机对照研究
Study Selection Pts MFT Results
CALGB-1ed trial >/=10N+
+/- TAM 结果无差别，paclitaxel 对无TAM 组有作用。 AC → Paclitaxel 组有5 例AL。
乳腺癌辅助化疗的临床研究 ---TAM/CAF vs TAM
SWOG Trial: 绝经后HR+, LN+
Regimen group 1 (n = 361) TAM alone 5yrs group 2 (n = 566) group 3 (n = 550) Results Arm 1 TAM (361) CAF followed by TAM CAF concurrently with TAM DFS 67% OS 79%
–
最佳的治疗应该联合各种治疗方式。
乳腺癌辅助化疗的适应症
NIH Consensus Development Conference 2000 4th 1. 大多数局限期乳癌，只要肿瘤直径 > 1 cm， 无论病人有无绝经，淋巴结有无转移，以及 激素受体状况，都应该接受辅助化疗。
2. 对于肿瘤 < 1cm， 淋巴结阴性病人，是否需
无治疗预计10年死亡率 70%（多个LN+） 30%（中危，LN-） 23 (70 57) 12 (30 18) 13(70 57) 7(30 23) 3(10 7) 4(70 66) 2(30 28) 1(10 9)
10%（肿瘤<1 cm，LN-） 5 (10 5)
乳腺癌的辅助治疗

内分泌 化疗 研究性治疗
提高剂量强度
B-25 doubled the dose and dose intensity

CTX from 1200 mg/m2 x 4 to 2400 mg/m2 x 2 then to 2400 mg/m2 x 4 Again, there was no apparent benefit Conclusion: If a 4-fold increase in dose and dose intensity for CTX does not improve outcome, it could nonetheless remain possible that dose escalations
含ADR方案优于无ADR方案


A randomized trial (Intergroup INT 0102)
Regimen high-risk group：肿瘤至少2 cm 或激素受体阴性，随机接受 CAF or CMF, 加或不加 tamoxifen 5 Y。 low-risk group: 肿瘤小于 2 cm ，ER/PR阳性或不明。不用辅助治疗。 Results: HR 死亡率：CAF组 8% ：CMF组 10% 加tamoxifen 7% ： 9%, 复发率： CAF组 15% ：CMF组18% 加tamoxifen 13% ： 15%, LRER+/死亡率： 4% 复发率： 11% 结论：研究表明含ADR的疗效有所提高且有一定临床意义(甚至十分低危 的病人)。
提高剂量强度
The NSABP conducted 2 studies：B-22 and B-25, patients with node-positive disease 4 doses of doxorubicin (60 mg/m2). B-22 2305 women were randomized to receive either standard doses of doxorubicin and cyclophosphamide (60/600 mg/m2 x 4) or intensified cyclophosphamide (1200 mg/m2 x 2) or intensified and increased cyclophosphamide (1200 mg/m2 x 4). Neither disease-free survival nor overall survival was improved with any of the higher or more intense doses. toxicity was significantly increased with the higher doses.
Taxol改善生存和总生存率，但是ADR剂量增加并未 提高效果， NIH 推荐：在ER(-)病人中继续观察疗效
乳腺癌辅助化疗的临床研究

NSABP B28 trial: LN+
Regimen:
group 1 AC × 4→ Paclitaxel 225mg/m2 × 4 (q3w)
group 2 AC × 4 only both group: TAM TAM > 50y < 50y all ER+和或PR+
by all 8 of CMF (AAAACCCCCCCC).

At 10-year follow-up, the latter remains significantly superior .
SWOG-led randomized trial (SWOG 9313/INT-0137)

This trial enrolled patients with 0-3 positive nodes and is closed but not yet reported. concurrent (less dose-dense) versus sequential (more dose-dense) doxorubicin and cyclophosphamide.
要化疗应个体化。
辅助化疗方案的选择

CMF, FAC, 和AC 是低危病人最常用的辅助化疗方案， Epi替代ADR在欧洲也常用。个别研究认为这些方案
很少或没有差别，但是一项包括6000例病人的综合分
析显示与CMF比，含有ADR方案优于不含ADR方案， 能使相对复发和死亡危险分别减少12% 和11%，绝对 复发和死亡危险分别减少3.2%和2.7%。

乳癌的内科治疗在减少复发，控制症状，提高生存质量，延长生
存等方面都已经取得了很大的进步。乳腺癌综合治疗在成人实体 瘤中最具有临床意义。
乳腺癌的辅助治疗
辅助化疗/内分泌治疗减少年复发和死亡率
Reduction in Reduction in annual odds annual odds of recurrence (%) of death(%) --------------------------------------------------------------------------------------50 TAM5y /none 45+/-8 32+/-10 50-59 TAM5y/none 37+/-6 11+/-8 60-69 TAM5y/none 54+/-5 33+/-6 < 40 poly-chemo/none 37+/-7 27+/-8 40-49 poly-chemo/none 35+/-5 27+/-5 50-59 poly-chemo/none 22+/-4 14+/-4 60-69 poly-chemo/none 18+/-4 8+/-4 pt age Therapy
beyond this level are beneficial. However, these studies do not support this
concept and suggest that outside of appropriate clinical trials, doses beyond 600 mg/m2 are not justifiable.
Italian trial Japanese trial PEGASE 01 >/= 4 N+ >/=10N+ >/=10N+
785
382 97 314
5.1yrs
4.3yr 4yrs 3.3yrs
No differ
No differ No differ increased DFS (17% vs 55%) 37th ASCO
乳腺癌新辅助化疗---每周泰素或 每3周泰素（+FAC)对照研究
MDACC phase III study: 病理CR率
Regimen
Group 1 Taxol 80mg/m2 qw×12→FAC ×4 →Surgery
Group 2 Taxol 225mg/m2 civ 24hrs q3w ×4→FAC ×4→Surgery Results LN- (n = 53) LN+ (n = 72) weekly 31% 31% every 3weeks 19% 11%
乳腺癌的内科治疗
乳腺癌的内科治疗

乳腺癌是女性最常见的肿瘤，女性肿瘤死因第二位。 美国85岁以 下女性每9人中1人患乳腺癌。 乳腺癌是一种全身性疾病， 在乳腺癌早期可能存在着微小转移灶，

除0或1期较早的病人以外，几乎各期病人都在一定时期需要内科
治疗。

内科治疗主要包括化疗和内分泌治疗，单克隆抗体等。
CALGB 9741

A critical trial, completed but not reported, in which 2005 patients were randomly assigned to treatment every third week (less dose-dense) or every other week (more dose-dense).
EBCTCG 1995 Lancet 1998
辅助化疗或内分泌治疗 10年减少死亡率绝对值
每年减少死亡率
-------------------------------------------------------------------------------------.50 .30 .10
----------------------------------------------------------------------------------------------------------
-Over 4400 patients


常用一线辅助化疗方案
FEC CEF120 ADR×4 →CMF ×3-4 AC: ADR 60mg/m2 IV d1 CTX 600mg//m2 IV d1
q3w×4
AC→T: AC ×4 Paclitaxol 175mg/m2 q3w×4
乳腺癌辅助化疗的临床研究