[표지]

목차

인사말 / 손숙미 3

환영사 / 이진수 4

프로그램 5

NCI Drug Development Program : Overview and Future Directions(NCI 항암제 개발의 현 주소 : 의사결정과정 및 FDA와의 협력 등) / James H. Doroshow 6

[저자소개] 8

History of NCI's Drug Development Program: 1955 to Present 10

Why was NCI in the Cancer Drug Development Business in 1955? 11

Anticancer Drugs Discovered & Developed by NCI from Preclinical Stage 11

NCI U.S. Clinical Trials Treatment Sites 12

Cooperative Group Trials 12

NCI-sponsored Clinical Trials Contributing to FDA-approved Indications for New Agents 13

Cancer Therapeutics Development : Role of NCI 13

Scope of NCI's Drug Development Program 14

Organization of the Division of Cancer Treatment & Diagnosis 15

Drug Development Program: NCI & NIH 15

Decentralized NCI Drug Development 16

NCI Experimental Therapeutics Program 16

2009 and Beyond: Moving Toward One NCI Pipeline-A Centralized Decision Body to Support Discovery and Development Activities 17

A Unified Approach to NCI Experimental Therapeutics-One Pipeline-Multiple Inputs 18

Standard Drug Development Timeline 19

Most Drugs Fail in Late Stages of Development-Particularly in Oncology 19

Current Stages of Therapeutics Development 20

Match the Technology to the Task 20

Modeling an Efficient Cancer Drug Development Paradigm for the Future 21

Efficiently Assessing Target Effects and Early Evidence of Clinical Benefit 21

Is Response Rate Even the Question? 22

Randomized Discontinuation Design 22

What Type of Patients to Enroll? 23

Why Focus On A "Specified Tumor Type"? 23

Hierarchical Clustering: Colon and Rectal Cancer Cluster Separately: By Disease & Stage 24

Why Focus On A "Specified Tumor Type"? 24

Broad Disease Screening in Phase II Trials: Back to the Future 25

"Broad" Phase II Trial of Doxorubicin 25

Broad Phase II Trial Considerations 26

Target Inhibition as the Endpoint of a Phase II Trial: Proof of Concept Study of Oral Topotecan in Advanced Solid Neoplasms Expressing HIF-1α 26

Pilot Study of Oral Topotecan in Advanced Solid Neoplasms Expressing HIF-1α 27

What Is the Definition of "A Drug"? 27

Minimum Data Sets Necessary to Demonstrate Safety and Efficacy 28

NCI Cooperative Group Date Mgt/Monitoring 28

Streamlined Data Collection: Current Practice 29

Streamlined Data Collection - Adverse Events 29

NCI Cooperative Group Program: On-Site Audits & Patient Case Review Categories 30

VIEW (Virtual Imaging Evaluation Workspace) 30

Clinical Trial Endpoints: Independent Central Radiologic Review 31

NCI Cooperative Group Program: How Much Data Is Enough? 31

Evolution of the Oncologic Drug Development Paradigm: Shortening the Timeline 32

Models of Cancer Drug Development: Present and Future 32

Accelerating NCI's Timeline to Personalized Medicine in Cancer Treatment 33

Introduction to Preclinical Discovery and Development of New Cancer Therapeutics at the NCI(NCI 전임상시험 프로그램(DTP) 소개 : Validation 과정을 중심으로) / Joseph E. Tomaszewski 34

[저자소개] 36

Order of Presentation 38

Mission Statement / Functional Statement of DCTD 39

From Bench to Bedside: The Concept 39

Therapeutics Development Timeline 40

NCI Experimental Therapeutics (NExT) Program for Drug Discovery and Development 40

FBC Goals 41

Functional Biology Space Concept 42

The Cancer Genome Atlas (TCGA) 42

NCI Experimental Therapeutics (NExT) Program for Drug Discovery and Development 43

NCI Chemical Biology Consortium (CBC) 44

NExT CBC Stage Gates 45

Lead Optimization 46

Enabling Lead Development Chemistry in CBC 46

Multiple Entry Points into the NExT/CBC Discovery/Development Pipeline 47

CBC Early Discovery Activities: Tdp1 Pilot with Pommier Laboratory 47

NCI Experimental Therapeutics (NExT) Program for Drug Discovery and Development 48

Drug Development Programs at the NCI & NIH 48

Decentralized NCI Drug Development 49

DTP Organizational Structure 49

DTP Comprehensive Pharmaceutical Services For Small Molecules 50

DTP GMP Manufacture of Bio-Pharmaceuticals 50

Preclinical Pharmacology and Toxicology 51

Drug Development Example Incorporating PK/PD Paradigm 51

Indenoisoquinolines 52

Study Design: New Top1 Inhibitors 52

Efficacy (A375) of New Top1 Inhibitors 53

γ-H2AX Dose Response to Topotecan in a Responsive Mouse Xenograft Model A375 (Human melanoma) at +4 Hrs After Single Dose 53

γ-H2AX Dose Response to NSC 724998 in Mouse Xenograft Model A375 (Human melanoma) at +2 Hrs After Single Dose 54

Dose/Response of γ-H2AX to Topo1 Inhibitors 54

Heat Map of PCR Expression(after in vivo administration of compounds to A375 xenografts) 55

Topotecan vs. New Top1 Inhibitors Human vs. Mouse Bone Marrow 55

New Top1 Inhibitor Eff/PK/PD Summary 56

Indenoisoquinoline Proof of Mechanism Randomized Phase I Trial 56

NCI Experimental Therapeutics (NExT) Program for Drug Discovery and Development 57

CTEP Clinical Development Program 57

CTEP Clinical Trials Treatment Program: Scope(2008) 58

Phase O Clinical Trials : Why Change the Paradigm? 58

Can The Pharmaceutical Industry Reduce Attrition Rates? 59

Exploratory IND & Phase O 59

Novel Approaches to Early Phase Personalized Trials 60

ABT-888 (PARP Inhibitor) NCI Phase O Clinical Trial Study Design 60

Phase O Pharmacodynamic Data: PBMC vs. Tumor 61

NCI's First Phase O - Timelines and What We Have Achieved 61

Drug Development and Approval Continues with NCI's Assistance 62

Critical Requirements for the Development of Personalized Cancer Treatment: Phase I-III Transition 62

Global Trend of Patent Application & Registration in Cancer Therapeutics and Patent Strategy(항암제와 관련한 글로벌 특허 출원·등록 동향 및 R&D 단계에서의 특허 출원 전략 / Myoung-jin Lee 64

[저자소개] 66

Contents 68

I. Global trend of patent application & registration in cancer therapeutics 69

Patent applications in cancer therapeutics(global trend, 1990~2007) 69

Patent applications in cancer therapeutics(KIPO, 1990~2007) 70

Recent global trend of patent applications in cancer therapeutics(2003~2007) 70

Patent applications in cancer therapeutics(KIPO, 2000~2007) 71

Patent applications v. patent registration in cancer therapeutics(KIPO, 2000~2007) 71

Patent applications related to antibody and gene therapy in cancer therapeutics(1990~2007) 72

Patent applications related to antibody and gene therapy in cancer therapeutics(2003~2007) 72

Top 10 applicants related to cancer in KIPO(Publication Date: 2006. 01. 01~2009. 09. 01) 73

Patent applications of major pharmaceutical companies in cancer therapeutics 73

Novatis 74

Genentech 74

II. Patent strategy 75

1. When planning of new drug development 76

2. When filing patent applications 77

3. Exercise of patent rights 83

Role of NCI's Cancer Therapy Evaluation Program in Anti-cancer Drug Development(NCI 항암신약 임상시험 프로그램(CTEP) 개관 / Edward L. Trimble 90

[저자소개] 92

NCI Divisions 94

Division of Cancer Treatment and Diagnosis 95

Cancer Therapy Evaluation Program(CTEP) 96

CTEP scientific process 96

CTEP Branches 97

CTEP partnership 97

CTEP government partnership 98

Sources of anti-cancer agents 98

Outreach process 99

Priorities for NCI review 99

NCI decision & negotiation 100

Key elements of CRADA 100

Key elements of CRADA: II 101

Process for anti-cancer agent in CRADA 101

Process for anti-cancer agents in CRADAs: II 102

Review of agent-specific data 102

Phase O trials 103

Phase I studies 103

Phase II trials 104

Discovering effective New Treatments for Children with Cancer 104

Definitive phase III trials 105

Specialized consortia: cont'd 105

Cooperative Groups 106

Cooperative groups: II 106

Cooperative groups: III 107

Oncology groups: IV 107

Clinical trials harmonization 108

Help tor investigators 108

CTEP portfolio of new anti-cancer agents 109

Examples of targeted novel agents under CTEP IND 109

Examples of targeted/novel agents under CTEP IND 110

CTEP Solicitations in Planned for 2009-2010: I 110

CTEP solicitations in planned for 2009-2010: II 111

Organ Dysfunction Group Study Agents: 1999-2009 111

Collaboration Among NCI, Industry and Research Community in The Clinical Development of Bevacizumab (Avastin) 112

Angiogenesis (formation of blood vessels) as the target of cancer therapy 112

Bevacizumab (Avastin) - A humanized monoclonal antibody against VEGF 113

Collaborative Research and Development Agreement(CRADA) for bevacizumab 113

Bevacizumab in 1997 114

Goals of the CTEP development plan for bevacizumab 114

1998 First CTEP-sponsored Bevacizumab Trial 115

Rationale for targeting VEGF in Renal Cell Cancer 115

Randomized Phase II trial in RCC (clear cell) -- Bevacizumab at two doses vs Placebo 116

Role of VEGF targeting agents in current standards of care for patients with advanced RCC 117

Examples of trials leading to FDA approval for expanded indications 117

FDA approval based of CTEP-sponsored Avastin trials 118

Clinical trials to explore activity in multiple tumors types and clinical settings 119

CTEP-sponsored trials - Exploring activities in expanded clinical indications 119

Trials for combination of targeted agents 120

Why combining targeted agents 120

Industry-NCI/CTEP-Investigator Agreements 121

Selected Clinical Trials with bevacizumab+investigational targeted agents 121

Selected CTEP-sponsored Trials - combinations of novel/targeted agents 122

Preliminary data indicating increased efficacy 122

Multi-arm or multi-cohort phase II trials for novel combinations 123

Correlative and biomarker studies - ongoing tasks 123

Summary 124

CTEP-sponsored Group Trials supporting FDA-approved indications for new agents and diagnostics 124

Trials supporting FDA approvals 125

Why we need international collaboration: I 126

Why we need international collaboration: II 126

Why we need international collaboration: III 127

NCI International Partnerships in Early Phase Trials 127

NCI International Partnerships in Late Phase Trials 128

Acknowledgements 128

Contact information 129

Case Presentations of Drug Development in Korea(국내사례 발표)(내용없음) 130

[뒷표지] 131