DEVELOPPEMENT THERAPEUTIQUE ET PHARMACOLOGIE CLINIQUE EN ONCOLOGIE PEDIATRIQUE

Clinical pharmacology studies of drugs for childhood malignancies aim at optimizing the use of available drugs and developing effective new agents. Clinical pharmacology data (in the areas of pharmacokinetics, pharmacogenetics, and pharmacodynamics) on inter- and intraindividual variations in drug disposition and drug effects in children can be used to design optimal dosage schedules associated with less toxicity and greater efficacy. This approach has been successful with high-dose methotrexate, busulfan conditioning of bone marrow transplant recipients, 6-mercaptopurine maintenance treatment for acute lymphoblastic leukemia, and carboplatin. Another goal is to develop effective new anticancer agents and treatment strategies for childhood malignancies. Current efforts are focusing on new drugs with novel mechanisms of action, cytokines with effects on immune function and hematopoiesis, drugs capable of reversing tumor resistance, and drugs that protect healthy tissues. Clinical pharmacology studies should follow strict methodological rules and should identify characteristics that are specific to children. They are of interest to clinicians, basic research investigators, and pharmaceutical companies. Together with immunotherapy and gene therapy, clinical pharmacology is one of the areas that can be expected to provide significant advances in the treatment of childhood cancer over the next ten years.