肿瘤的基本临床治疗方法
合集下载
相关主题
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
History of drug discovery
• Beginning of modern chemotherapy
– First clinical trial of Nitrogen mustard in Lymphoma at Yale in 1942
– Select a single type and stage of tumor – Selection of patients: measurable tumor, good
performance status, normal organ function – Many common solid tumors have standard treatment,
• Combination therapy
– Improved response and toxicity
• Comparison of these two therapies
Principles of Combination Chemotherapy
• Active as single agent • Non-overlapping toxicity • Synergistic efficacy • Different patterns of resistance • Optimal dose and schedule • Drug dose individualized
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
Chemotherapeutic Agents
• Alkylating Agents • Platinum Compounds • Antimetabolites • Purine Analogs • Adenosine Analogs • Topoisomerase I Inhibitors • Antitumor Antibiotics • Plant Alkaloids
Trastuzumab
Pertuzumab
T-DM1
Antibody: Trastuzumab
PP P
HER2
PP P
PP P
Cytotoxic: DM1
Stable linker: MCC
Emtansine
Nucleus
Spector NL, Blackwell KL. J Clin Oncol 2009; Nelson MH, et al. Ann Pharmacother 2006;
Targeted Agents and New Directions in Drug Development
• Tyrosine Kinase and Multikinase Inhibitors • Differentiating Agents • Angiogenesis Inhibitors • Monoclonal Antibodies • Proteosome Inhibitors • Histone Deacetylase Inhibitors • Gene Therapy • Vaccines
Anthracycline
• Effective in many tumors: LS, BC, STS… • Side effects:
– Bone marrow suppression – Cardiac toxicity
• Doxorubicin Epirubicin Pegylated liposome doxorubicin
Lewis Phillips GD, et al. Cancer Res 2008.
26
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
• Experimental animal tumor models • Human cancer cell lines
– Clinical trials
• Phase I, Phase II, PhaseBiblioteka BaiduIII
Phase I Trial
• Objectives
Describe pharmacokinetics and toxicity
复旦大学上海医学院肿瘤学系
Self Introduction
• Graduated from FUSMC • Medical Oncologist in Cancer Hospital • Major: Systemic Therapy for Breast Cancer
Systemic Therapy
Platinum
• Effective in many tumors: LU, BC, CRC… • Side effects
– Bone marrow suppression – Neuropathy, Renal function impairment
• Cisplatin Carboplatin Oxaliplatin
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
Single-agent and combination therapy
• Single-agent therapy
– Control symptoms in palliative therapy
• Cytotoxic drug
– MTD (maximally tolerated dose) – RTD (Recommended dose) – DLT (dose-limiting toxicity)
Phase II Trial
• Evaluate the potential efficacy of a new treatment
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
– Regressions of lymphomas generated excitement for chemotherapy
– Results published in 1946
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
ethical approach used to test new novel therapy before standard therapy (dilemma)
Phase III Trial
• Pivotal studies
– Help to establish a new treatment of standard – Prospective, randomized studies comparing a new
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
Clinical Use of Systemic Therapy
• Advanced and Metastatic Disease • Adjuvant Therapy • Neoadjuvant Therapy
Taxane
• Effective in many tumors: BC, LU, STS… • Side effects
– Bone marrow suppression – Hypersensitivity, Neuropathy
• Paclitaxel Docetaxel Albumin bound paclitaxel
Fudan University Shanghai Cancer Center
《Basic Clinical Oncology》 Fudan University Cancer Center
Bi Yun Wang (Associate Professor, Dept. of Medical Oncology)
treatment against established therapy or placebo – Balance prognostic pretreatment characteristics – Statistical calculation of sample size – Results provide powerful data to support clinical
Target therapy agents
• Gleevic • Rituximab • Cetuximab • Herceptin
Herceptin
• Target therapy to Her-2 amplification
– Breast cancer – Gastric cancer
• Effective
practice or even change guideline
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
Introduction
• Systemic therapy
– Chemotherapy – Hormonal therapy – Target therapy
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
– Adjuvant/Neoadjuvant – Metastatic setting
• Few adverse events as monotherapy
Targeted Therapies for HER2+ Breast Cancer:
Trastuzumab, Pertuzumab, and T-DM1
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
New drug development and clinical trials
• New drug development
– Screening to exploit new therapeutic targets – Basic cancer research
History of drug discovery
• Beginning of modern chemotherapy
– First clinical trial of Nitrogen mustard in Lymphoma at Yale in 1942
– Select a single type and stage of tumor – Selection of patients: measurable tumor, good
performance status, normal organ function – Many common solid tumors have standard treatment,
• Combination therapy
– Improved response and toxicity
• Comparison of these two therapies
Principles of Combination Chemotherapy
• Active as single agent • Non-overlapping toxicity • Synergistic efficacy • Different patterns of resistance • Optimal dose and schedule • Drug dose individualized
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
Chemotherapeutic Agents
• Alkylating Agents • Platinum Compounds • Antimetabolites • Purine Analogs • Adenosine Analogs • Topoisomerase I Inhibitors • Antitumor Antibiotics • Plant Alkaloids
Trastuzumab
Pertuzumab
T-DM1
Antibody: Trastuzumab
PP P
HER2
PP P
PP P
Cytotoxic: DM1
Stable linker: MCC
Emtansine
Nucleus
Spector NL, Blackwell KL. J Clin Oncol 2009; Nelson MH, et al. Ann Pharmacother 2006;
Targeted Agents and New Directions in Drug Development
• Tyrosine Kinase and Multikinase Inhibitors • Differentiating Agents • Angiogenesis Inhibitors • Monoclonal Antibodies • Proteosome Inhibitors • Histone Deacetylase Inhibitors • Gene Therapy • Vaccines
Anthracycline
• Effective in many tumors: LS, BC, STS… • Side effects:
– Bone marrow suppression – Cardiac toxicity
• Doxorubicin Epirubicin Pegylated liposome doxorubicin
Lewis Phillips GD, et al. Cancer Res 2008.
26
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
• Experimental animal tumor models • Human cancer cell lines
– Clinical trials
• Phase I, Phase II, PhaseBiblioteka BaiduIII
Phase I Trial
• Objectives
Describe pharmacokinetics and toxicity
复旦大学上海医学院肿瘤学系
Self Introduction
• Graduated from FUSMC • Medical Oncologist in Cancer Hospital • Major: Systemic Therapy for Breast Cancer
Systemic Therapy
Platinum
• Effective in many tumors: LU, BC, CRC… • Side effects
– Bone marrow suppression – Neuropathy, Renal function impairment
• Cisplatin Carboplatin Oxaliplatin
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
Single-agent and combination therapy
• Single-agent therapy
– Control symptoms in palliative therapy
• Cytotoxic drug
– MTD (maximally tolerated dose) – RTD (Recommended dose) – DLT (dose-limiting toxicity)
Phase II Trial
• Evaluate the potential efficacy of a new treatment
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
– Regressions of lymphomas generated excitement for chemotherapy
– Results published in 1946
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
ethical approach used to test new novel therapy before standard therapy (dilemma)
Phase III Trial
• Pivotal studies
– Help to establish a new treatment of standard – Prospective, randomized studies comparing a new
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
Clinical Use of Systemic Therapy
• Advanced and Metastatic Disease • Adjuvant Therapy • Neoadjuvant Therapy
Taxane
• Effective in many tumors: BC, LU, STS… • Side effects
– Bone marrow suppression – Hypersensitivity, Neuropathy
• Paclitaxel Docetaxel Albumin bound paclitaxel
Fudan University Shanghai Cancer Center
《Basic Clinical Oncology》 Fudan University Cancer Center
Bi Yun Wang (Associate Professor, Dept. of Medical Oncology)
treatment against established therapy or placebo – Balance prognostic pretreatment characteristics – Statistical calculation of sample size – Results provide powerful data to support clinical
Target therapy agents
• Gleevic • Rituximab • Cetuximab • Herceptin
Herceptin
• Target therapy to Her-2 amplification
– Breast cancer – Gastric cancer
• Effective
practice or even change guideline
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
Introduction
• Systemic therapy
– Chemotherapy – Hormonal therapy – Target therapy
Outlines
• History of Drug Discovery • New drug development and clinical trials • Chemotherapy Development • Targeted Agents and New Directions in Drug
– Adjuvant/Neoadjuvant – Metastatic setting
• Few adverse events as monotherapy
Targeted Therapies for HER2+ Breast Cancer:
Trastuzumab, Pertuzumab, and T-DM1
Development • Clinical Uses of Systemic Therapy • Systemic Therapy Process
New drug development and clinical trials
• New drug development
– Screening to exploit new therapeutic targets – Basic cancer research