Metronomic Chemotherapy, 1

At the end of the 1990s, researchers began to investigate the antiangiogenic activity of frequent administration of low-dose chemotherapeutic drugs, as a mechanism potentially contributing to their antineoplastic activity in vivo. During the past decade, a number of studies have shown that such metronomic chemotherapy has preclinical and clinical activity that may be ascribed to various mechanisms of action, including the inhibition of angiogenesis and the induction of an increase in the immunological response. Numerous phase I and phase II clinical trials have investigated the use of metronomic chemotherapy in different tumors and phase III clinical trials are currently ongoing. This book analyzes all aspects of this new therapeutic approach and its possible future development. After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug and on the potential role of combination agents such as tyrosine kinase inhibitors and monoclonal antibodies are discussed. Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacodynamics, pharmacogenetics, pharmacoeconomics and adverse drug reactions. The book closes by describing the role of this therapy in the veterinarian clinic.