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
– 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
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
Fudan University Shanghai Cancer Center
《Basic Clinical Oncology》 Fudan University Cancer Center
Bi Yun Wang (Associate Professor, Dept. of Medical Oncology)
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
Anthracycline
• Effective in many tumors: LS, BC, STS… • Side effects:
– Bone marrow suppression – Cardiac toxicity
• Doxorubicin Epirubicin Pegylated liposome doxorubicin
Taxane
• Effective in many tumors: BC, LU, STS… • Side effects
– Bone marrow suppression – Hypersensitivity, Neuropathy
• Paclitaxel Docetaxel Albumin bound paclitaxel
– 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,
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
Outபைடு நூலகம்ines
• 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
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
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
• 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
• Experimental animal tumor models • Human cancer cell lines
– Clinical trials
• Phase I, Phase II, Phase III
Phase I Trial
• Objectives
Describe pharmacokinetics and toxicity
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
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;
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
• Cytotoxic drug
– MTD (maximally tolerated dose) – RTD (Recommended dose) – DLT (dose-limiting toxicity)
Phase II Trial
• Evaluate the potential efficacy of a new treatment
Platinum
• Effective in many tumors: LU, BC, CRC… • Side effects
– Bone marrow suppression – Neuropathy, Renal function impairment