The Role of Pharmacology in Pediatric Oncology (Developments in Oncology, 44)

The dramatic improvement made in recent years in the treatment of child­ hood malignancies has been in large part the result of advances in the field of pharmacology. Chemotherapy is the major therapeutic modality used to treat childhood cancer. Rational administration of antineoplastic chemo­ therapy to the child with cancer requires the pediatric oncologist to have a thorough understanding of the fundamental principles of clinical pharmaco­ logy, an intimate knowledge of the specific agents being used, and an aware­ ness of the unique biologic and physiologic features of children. In mid 1985, a distinguished group of pediatric oncologists and clinical pharmacologists convened in a unique workshop to review the subject of pharmacology in pediatric oncology. A goal of this workshop was to pro­ duce a book which would review this topic and present it in a format useful for the clinician. In this book basic principles of pharmacology, mechanisms of drug resis­ tance, new methods of drug delivery, guidelines for studying new agents in children, new biological response modifiers and the pharmacology of the most commonly used chemotherapeutic agents in children are reviewed in depth. Particular emphasis is given to discussing those topics which unique­ ly apply to the use of antineoplastic agents in children with cancer. The Editors VII Contents Preface . v Contents Vll List of Major Contributors Xl Principles of Antineoplastic Therapy in Children 1. Clinical pharmacokinetics for the pediatric oncologist ................ . Front Matter....Pages I-XII Front Matter....Pages 1-1 Clinical Pharmacokinetics for the Pediatric Oncologist....Pages 3-13 The pharmacology of antineoplastic agents in children....Pages 15-27 Clinical pharmacology of anticancer drugs in children: differences and similarities between children and adults....Pages 29-71 Front Matter....Pages 73-73 Drug resistance in medical and pediatric oncology....Pages 75-87 Genetic reasons for pharmacologic treatment failure: gene amplification....Pages 89-95 New approaches to overcome drug resistance....Pages 97-112 Front Matter....Pages 113-113 New methods of administering old drugs: IV infusion of mercaptopurine....Pages 115-123 Regional therapy: an overview....Pages 125-135 Pharmacologic approaches to the treatment of central nervous system malignancy....Pages 137-156 Front Matter....Pages 157-157 Phase I and II trials in pediatric cancer patients: a rationale....Pages 159-170 Guidelines for conduct of Phase I studies in children....Pages 171-176 Front Matter....Pages 177-177 Factors affecting the clinical pharmacology of antileukemic drugs....Pages 179-184 Potentiation of 6-mercaptopurine after time and dose-dependent pretreatment with methotrexate in malignant human T- and B-lymphoblasts....Pages 185-191 The effect of methotrexate on purine and pyrimidine deoxyribonucleoside triphosphate pools and on cell viability and cell-phase distribution in malignant human T- and B-lymphoblasts....Pages 193-200 7-Hydroxy-methotrexate production after methotrexate therapy....Pages 201-204 Front Matter....Pages 205-205 An overview of adverse late effects of cancer chemotherapy in children....Pages 207-215 Focusing on late effects in long-term survivors of childhood leukemia and lymphomas....Pages 217-233 Front Matter....Pages 235-235 Purging procedures: a critical step in autologous bone marrow transplantation....Pages 237-253 ‘High dose’ cisplatinum: a phase II study....Pages 255-261 Front Matter....Pages 263-263 Induction of differentiation: a possible therapeutic approach to the treatment of hematologic malignancy....Pages 265-273 Front Matter....Pages 263-263 The development of 9-substituted purines as immunomodulators....Pages 275-284 Immunopharmacologic profile of an L-Arginine hypoxanthine derivative: PCF/01....Pages 285-293 Antineoplastic drugs modulating c-myc expression in K562, induce erythroid differentiation and modify, with IFN, susceptibility to NK cell mediated lysis....Pages 295-301 In vivo treatment with recombinant interleukin-2 (IL-2) stimulates the differentiation of natural killer (NK) precursor cells....Pages 303-307 Immunopharmacology studies related to in vitro infection with HTLV-I....Pages 309-319 Back Matter....Pages 321-322