ADT Chemo CRPC治疗进展
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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
Results:
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Patient characteristics
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Treatment effect by metastatic status: FFS
2015-07-18, Beijing
<br /><br />E3805<br />CHAARTED: ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer
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
Zoledronic acid: Failure-free survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Zoledronic acid: Survival
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
• 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
• 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
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？
2015-07-18, Beijing
Docetaxel: Survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Docetaxel: Survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Slide 1
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
Consistency of treatment effect
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Consistency of treatment effect
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
百度文库
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
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
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Zoledronic acid + docetaxel: Survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
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
2015-07-18, Beijing
Accrual
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Accrual
Presented By Nicholas James at 2015 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
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
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
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
OS by extent of metastatic disease at start of ADT
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
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
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
• 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
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Study Endpoints
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Docetaxel: Failure-free survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
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
Results:
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Patient characteristics
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Treatment effect by metastatic status: FFS
2015-07-18, Beijing
<br /><br />E3805<br />CHAARTED: ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer
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
Zoledronic acid: Failure-free survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Zoledronic acid: Survival
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
• 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
• 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
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？
2015-07-18, Beijing
Docetaxel: Survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Docetaxel: Survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Slide 1
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
Consistency of treatment effect
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Consistency of treatment effect
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
百度文库
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
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
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Zoledronic acid + docetaxel: Survival
Presented By Nicholas James at 2015 ASCO Annual Meeting
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
2015-07-18, Beijing
Accrual
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Accrual
Presented By Nicholas James at 2015 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
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
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
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
OS by extent of metastatic disease at start of ADT
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
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
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
• 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
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
2015-07-18, Beijing
Study Endpoints
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
Presented By Nicholas James at 2015 ASCO Annual Meeting
2015-07-18, Beijing
Docetaxel: Failure-free survival
Presented By Nicholas James at 2015 ASCO Annual Meeting