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ADT Chemo CRPC治疗进展
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
E3805 – CHAARTED Treatment
HV: visceral metastases and/or 4 or more bone metastases
2015-07-18, Beijing
Primary endpoint: Overall survival
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Causes of Death
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Hematologic Toxicity (%)
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Conclusion
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Docetaxel: Survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Zoledronic acid + docetaxel: Failure-free survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Treatment effect by metastatic status: FFS
2015-07-18, Beijing
Therapy beyond progression
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Chemotherapy Doses Given
2015-07-18, Beijing
Consistency of treatment effect
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Consistency of treatment effect
ADT + Docetaxel benefited all subgroups
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Secondary Endpoints
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Zoledronic acid: Failure-free survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Zoledronic acid: Survival
• Charles Brenton Huggins (1901-1997) • 1941年,内分泌治疗转移 性前列腺癌 • 1966年诺贝尔医学奖
2015-07-18, Beijing
2015-07-18, Beijing
ADT的种类
• 抑制雄激素的分泌
– 睾丸:手术/药物去势----CRPC – 肾上腺
2015-07-18, Beijing
Patient characteristics
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Patient characteristics
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
• AR拮抗剂:比卡鲁胺,氟他胺。比卡鲁胺150mg vs 去势 • CAB:生存优势< 5%,不广泛推荐
2015-07-18, Beijing
ADT的种类
• 抑制肾上腺类固醇生成
酮康唑,氨鲁米特,皮质激素 阿比特龙
CYP17(类固醇17-α-羟化酶)选择性抑制剂,抑制雄激素合成, 酮康唑效力的10-30倍
2015-07-18, Beijing
Inclusion criteria
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Inclusion criteria
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
晚期前列腺癌-------ADT/Chemo/CRPC治疗进展
北京大学第一医院 北京大学泌尿外科研究所 宋 毅
2015-07-18, Beijing
晚期前列腺癌的治疗方法
• • • • • ADT 化疗 免疫治疗 核素治疗 靶向治疗?
2015-07-18, Beijing
2015-07-18, Beijing
OS by extent of metastatic disease at start of ADT
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
TAK700
• 恩杂鲁胺 恩杂鲁胺:新型 :新型AR拮抗剂
阻断AR向细胞核内转运与DNA结合
2015-07-18, Beijing
ADT的一些问题
• Flare-up • CAB • AR拮抗剂单药治疗 • iADT = intermittent castration • 即刻 or 延迟ADT (asymptomatic) • 联合化疗:是否需要组合拳?
• 阻断雄激素受体的作用
– 受体拮抗剂
2015-07-18, Beijing
2015-07-18, Beijing
ADT的种类
• 手术去势
睾酮去势水平:< 50 ng/dL(1.7 nmol/L);< 20 ng/dL 12hr内达到去势
• 雌激素:己烯雌酚(DES),二线 • 药物去势
LHRH agonists:2 - 4周,10% - 15%达不到去势,疗效相当 (Andrew Schally 1971年发现) LHRH antagonists :abarelix ,degarelix,3天
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Early Chemo+ADT: A debate in one slide – a need for randomized phase 3 trial
2015-07-18, Beijing
Outcome measures
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Outcome measures
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Outcome measures
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Outcome measures
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Docetaxel: Survival
Presented By Nicholas James at 2015 ASCijing
Docetaxel: Survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Non-Hematologic Toxicity (%)
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Accrual
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing