Intraperitoneal Therapy for Ovarian Cancer (eBook)

Prof. Alberts is Director of the Arizona Cancer Center in Tucson, AZ. He led a workshop on intraperitoneal chemotherapy in January 2006 at the Gynecologic Oncology Group meeting with 400 oncologists and nurses present. He also published the results of the first ever phase III trial comparing IV to IP chemotherapy in the New England Journal of Medicine.

Intraperitoneal Therapy for Ovarian Cancer 2
Acknowledgment 4
Contents 5
1: Introduction 7
References 11
2: Current Chemotherapy of Ovarian Cancer 13
2.1 Trials that Define Primary Treatment 13
2.2 Optimal Integration of Taxanes 15
2.3 Integration of a Third Cytotoxic Agent 16
2.4 New Approaches Targeting the Mitotic Apparatus 17
2.5 Development of Alternative Cytotoxic Agents 18
2.6 Biologic Principles with an Impact on Primary Therapy 18
2.7 Targeting Angiogenesis 21
2.8 Chemotherapy Resistance 21
2.9 Synthetic Lethal Strategies 23
2.10 Discussion 24
References 25
3: Principles of Intraperitoneal Chemotherapy 32
3.1 Introduction 32
3.2 Rationale for the Delivery of Antineoplastic Agents by the IntraperitonealRoute as a Treatment for Intraperitoneal Malignan 32
3.2.1 Anatomic Location of the Cancer 32
3.2.2 General Physiology of the Peritoneal Cavity Relevant for Intraperitoneal Antineoplastic Drug Delivery 33
3.2.3 Evidence of Concentration-Dependent Biological Activity of an Antineoplastic Agent 34
3.3 Limitations of Intraperitoneal Antineoplastic Drug Delivery 35
3.3.1 Local Toxicity of Antineoplastic Agents 35
3.3.2 Adequacy of Drug Distribution 35
3.3.3 Limited Direct Penetration of Antineoplastic Agents into Tumor Masses 36
3.3.4 Importance of Drug Delivery by Capillary Flow 36
3.3.5 Other Relevant Issues Defining the Use of Intraperitoneal Chemotherapy 37
3.4 Conclusion 37
References 38
4: Intraperitoneal Chemotherapy:Phase III Trials 41
4.1 Introduction 41
4.2 SWOG 8501/GOG 0104/EST 3885 42
4.3 GOG 0114/SWOG 9227/ECOG-GO 114 44
4.4 GOG 0172 46
4.5 Future Phase III IP Trials 51
4.6 Conclusion 52
References 53
5: Criteria for Using Intraperitoneal (IP) Chemotherapy for Advanced Ovarian Cancer 55
5.1 Frontline Therapy 55
5.1.1 Impact of the Size of Residual Disease 55
5.1.2 Impact of Chemical Debulking Prior to IP Therapy 56
5.1.3 Impact of Disease Stage 57
5.2 Consolidation Therapy 57
5.2.1 Consolidation Therapy for Patients with no Residual Disease 57
5.2.2 Consolidation Therapy for Patients with Minimal Residual Disease 58
5.2.3 Impact of Retroperitoneal Disease 58
5.2.4 Impact of Stage IV Disease 59
5.2.5 Presence of Adhesions 60
5.3 Conclusions 60
References 61
6: Selection and Placement of Intraperitoneal Catheters for IP Chemotherapy for Ovarian Cancer 63
6.1Introduction 63
6.2Background on IP Catheters 65
6.3 Peritoneal Catheter Placement at Primary Surgery for Presumed Ovarian Cancer 68
6.4 Radical Surgical Procedures 68
6.5 Choice of Device and Catheter 69
6.6 Technique for Placement at Laparotomy 70
6.7 Prevention of Catheter Failures 71
6.8 Prevention of Adhesions 75
6.9 Delayed Insertion of Peritoneal Catheter 75
6.10 Interventional Radiology Placement 76
6.11 Removal of the Catheter 77
6.12 Conclusions 77
References 78
7: Selection of Drugs for Intraperitoneal Chemotherapy for Ovarian Cancer 81
7.1 Introduction 81
7.2 Pharmacologic Principles of Intraperitoneal Therapy 82
7.3 Relative Clearances and First Pass Metabolism 82
7.4 Tumor Penetration 83
7.5 Intraperitoneal Drug Distribution 85
7.6 Principles for the Selection of Drugs for Intraperitoneal Administration 85
7.7 Pharmacokinetics of Intraperitoneally Administered Cisplatin, Carboplatin, and Paclitaxel 86
7.8 Neutralizing Agents 88
7.9 Strategies for Improving Drug Penetration 89
References 90
8: Administration Guidelines for Intraperitoneal Chemotherapy for Ovarian Cancer 93
8.1 Introduction 93
8.2 Selection of Patients for IP Chemotherapy 93
8.3 Positioning the Patient 94
8.4 Premedications Before IP Therapy 94
8.5 Accessing the IP Port 95
8.6 Delivery of IP Therapy 95
8.7 Trouble-Shooting Problems with IP Administration 96
8.8 Long-Term Tolerability of IP Chemotherapy 97
8.9 Summary 98
References 98
9: Novel Drugs for Intraperitoneal Therapy for Ovarian Cancer 99
9.1 Introduction 99
9.2 Therapeutic IP Approaches: The Next Generation Carboplatin 101
9.2.1 Oxaliplatin 101
9.2.2 Floxuridine (FUDR) 102
9.2.3 Topotecan 103
9.2.4 Irinotecan 103
9.2.5 Gemcitabine 103
9.3 Other Methods to Potentiate IP Cisplatin 104
9.4 Radioimmunotherapy 104
9.5 Immune Modulation and Antibodies 105
9.6 Bevacizumab 106
9.7 Discussion 107
References 107
10: Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy: An Ongoing Research Effort 113
10.1 Introduction 113
10.2 A Comprehensive Approach for Ovarian Cancer Treatment 114
10.3 Selection Criteria for a Comprehensive Treatment Plan 115
10.4 Quantitative Prognostic Indicators 115
10.5 Surgical Techniques Used to Achieve a Complete Cytoreduction in Selected Patients 117
10.5.1 Patient Preparation for Surgery 118
10.6 Anterior Parietal Peritonectomy and Complete Abdominal Exploration 118
10.7 Right and Left Subphrenic Peritonectomies 120
10.8 Greater and Lesser Omentectomy 121
10.9 Pelvic Peritonectomy with Rectosigmoid Colon Resection 121
10.10 Rationale for Heated Intraoperative Intraperitoneal Chemotherapy and Early Postoperative Intraperitoneal Chemotherapy 122
10.10.1 Technique for Heated Intraoperative Intraperitoneal Chemotherapy 124
10.10.2 Technique for Early Perioperative Intraperitoneal Chemotherapy 125
10.10.3 Modifications of Surgical Practice with Cytoreduction and Multiagent Perioperative Chemotherapy 125
10.11 Results of Comprehensive Treatment in Advanced Primary and Recurrent Ovarian Cancer 126
10.12 Morbidity and Mortality 128
10.13 The Peritoneum as a First Line of Defense Against Carcinomatosis 128
10.14 Comparison of Ovarian and Appendiceal Cancer 128
10.15 Conclusions 129
References 129
11: Health-Related Quality of Life and Patient-Reported Outcomes 132
11.1 Introduction 132
11.2 Measuring Patient-Reported Outcomes (PRO) 135
11.3 Quality of Life and Patient-Reported Outcomes of Intraperitoneal Therapy 143
11.4 Conclusion 146
References 146
Index 153