Cancer Chemotherapy: an Introduction

This book is intended as an introduction to the drug treatment of cancer. It is almost ten years since the last edition was written. In the intervening time, there have been numerous developments in cancer chemotherapy and in order to cover these the majority of the text has been completely revised and rewritten. In addition, two new chapters have been introduced, one on the safe handling of cytotoxic drugs and the other on biological response modifiers. In order to incorporate this new information without any undue increase in the length of the text the chapters on a combined approach to treatment have been omitted. This is not because interdisciplinary collaboration is no longer considered important but is a reflection of the fact that, in most centres, it has become the norm in cancer management and its central role in successful treatment no longer needs to be stressed quite so strongly. The four chapters in the last edition which dealt with the team approach to cancer therapy have been replaced by a single chapter on the place of chemotherapy in the overall treatment of cancer. Unfortunately, despite all the innovations of the last decade, it has become increasingly clear that much of the promise offered by drug treatment during the 1960s and 1970s has not been fulfilled.

Section 1 The Principles of Cytotoxic Drug Therapy.- 1 Principles of Tumour Growth.- Mitosis.- Nucleic Acids.- Duplication of DNA.- The Cell Cycle.- Kinetic Implications of the Cell Cycle.- Cell Loss.- Resting Cells.- Natural History of Tumour Growth.- Cell Numbers and Tumour Growth.- 2 The Effects of Cytotoxic Drugs on Normal Tissues.- Bone Marrow.- Gastrointestinal Tract.- Direct Effects on the Gastrointestinal Epithelium.- Nausea and Vomiting.- The Skin.- The Unborn Child.- Male Fertility.- Female Fertility.- Carcinogenicity.- 3 The Pharmacology of Cytotoxic Drugs.- Drug Dosage.- Alkylating Agents.- Mode of Action.- The Nitrogen Mustards.- Aziridines.- Dimethanesulphonates.- Nitrosoureas.- Expoxides.- Antimetabolites.- Mode of Action.- The Vinca Alkaloids.- Mode of Action.- Antimitotic Antibiotics.- Anthracycline Antibiotics.- Non-anthracycline Antibiotics.- Miscellaneous Compounds.- Non-classical Alkylating Agents.- Anthracenediones.- Epipodophyllotoxins.- Hydroxyurea (Hydrea).- Amsacrine (Amsidene, AMSA).- Enzyme Therapy.- 4 The Rationale of Cytotoxic Drug Therapy.- Tumour Regression and Cure.- Single Agent Continuous Therapy.- Fractional Cell Kill.- Combination Chemotherapy.- Intermittent Chemotherapy.- Scheduling of Therapy.- Tumour Growth Fraction.- Drug Access.- Drug Resistance.- Timing of Cytotoxic Therapy.- Adjuvant Therapy.- Neo-adjuvant Therapy.- Choice of Drugs for Combination Therapy.- Cytotoxic Drugs and the Cell Cycle.- Alternating Non-cross Resistant Regimes.- Drug Dose.- Reduced Toxicity.- Continuous Infusion Chemotherapy.- 5 The Management of the Side Effects of Cytotoxic Drugs.- Routine Precautions.- Bone Marrow Toxicity.- Leucopenia.- Thrombocytopenia.- Anaemia.- Nausea and Vomiting.- Alopecia.- Drug Extravasation.- Antagonism of Cytotoxic Action.- Leucovorin.- Mesna.- 6 The Safe Handling of Cytotoxic Drugs.- Precautions During the Preparation of Injectable.- Precautions for of Administration Cytotoxic Drugs.- 7 Resistance to Cytotoxic Drugs.- General Factors.- Timing of Drug Administration.- Anatomical Isolation.- Drug Antagonism.- Antibody Formation.- Cellular Factors Causing Drug Resistance.- Alterations to the Cell Membrane.- Increased Drug Deactivation.- Loss of Drug Activation Process.- Increased Production of Target Molecule.- Change in Enzyme Specificity.- Production of Non-essential Competitors.- Alternative Biochemical Pathways.- Repair of Cytotoxic Damage.- Prevention of Drug Resistance.- Cross Resistance.- 8 Alternative Methods of Cytotoxic Drug Administration.- Central Venous Access.- Intra-arterial Therapy.- Head and Neck Cancer.- Hepatic Metastases.- Malignant Melanoma and Soft Tissue Sarcomas.- A Note on Terminology.- Intrapleural Therapy.- Intraperitoneal Therapy.- Control of Ascites.- Control of Tumour.- Intravesical Therapy.- Intrathecal Therapy.- Topical Therapy.- 9 The Development and Assessment of New Cytotoxic Drugs.- Preclinical Testing.- Clinical Evaluation.- Phase I Studies.- Phase II Studies.- Phase III Studies.- Criteria of Assessment.- Cure.- Survival.- Response.- Palliation.- Conclusion.- Section 2 Biological Response Modifiers.- 10 Biological Response Modifiers.- Monoclonal Antibodies.- Lymphokines.- Interferons.- Interleukin-2.- Tumour Necrosis Factor.- Oncogenes.- Growth Factors.- Section 3 The Principles of Endocrine Therapy.- 11 The Development and Rationale of Endocrine Therapy.- The Cellular Basis for Hormonal Sensitivity in Breast Cancer.- Clinical Correlations of Oestrogen Receptor Status.- Carcinoma of the Prostate.- Endometrial Carcinoma.- Renal Cell Carcinoma.- Carcinoma of the Thyroid Gland.- Glucocorticoids and Cancer Therapy.- 12 The Clinical Pharmacology of Endocrine Drugs.- Anti-oestrogens.- Tamoxifen.- Inhibitors of Steroid Synthesis.- Aminoglutethimide.- Oestrogens.- Androgens.- Anti-androgens.- Cyproterone Acetate (Androcur, Cyprostat).- Flutamide.- LHRH Analogues.- The Progestins.- The Glucocorticoids.- Section 4 The Clinical Role of Chemotherapy.- 13 The Place of Chemotheraphy in Cancer Treatment.- Advantages and Limitations of Available Treatment Modalities.- The Objectives of Cancer Treatment.- 14 Childhood Cancer.- Wilms’ Tumour.- Neuroblastoma.- Central Nervous System (CNS) Tumours.- Rhabdomyosarcoma.- Ewing’s Sarcoma.- Retinoblastoma.- 15 Haematological Cancers.- Acute Lymphoblastic Leukaemia.- Acute Myeloid Leukaemia.- Chronic Myeloid Leukaemia.- Chronic Lymphoid Leukaemia.- B-cell CLL.- Hairy-cell leukaemia.- Hodgkin’s Disease.- Non-Hodgkin’s Lymphoma.- Polycythaemia Vera.- Multiple Myeloma.- 16 Solid Tumours.- Lung Cancer.- Small Cell Lung Cancer.- Non-small Cell Lung Cancer.- Carcinoma of the Breast.- Early Breast Cancer.- Advanced Breast Cancer.- Gastrointestinal Cancer.- Genitourinary Cancer.- Carcinoma of the Prostate.- Carcinoma of the Kidney.- Carcinoma of the Bladder.- Testicular Cancer.- Gynaecological Cancer.- Carcinoma of the Cervix.- Carcinoma of the Endometrium.- Carcinoma of the Ovary.- Choriocarcinoma.- Head and Neck Cancer.- Malignant Melanoma.- Brain Tumours.- Osteogenic Sarcoma.- Soft Tissue Sarcomas.