Mechanisms of action of low-dose metronomic chemotherapy

Abstract

Evidence from a growing body of preclinical and clinical studies points to the efficacy of continuously administrating anticancer chemotherapeutic drugs in low doses. This relatively new treatment strategy concept is called low-dose metronomic (LDM) chemotherapy. The therapeutic efficacy of LDM has been assessed for reducing the tumor load during the acute phase and in delaying relapse during the maintenance phase. The major benefits found in using LDM include the lack of major toxicities or complications as compared to conventional chemotherapy regimens and improved quality of life. Traditional therapeutic modalities in oncology aim toward more specific tumor targets at the tumor microenvironment, whereas LDM chemotherapy acts on a broad spectrum of mechanisms, some of which are still not clear. We will discuss in this chapter several possible LDM chemotherapy anticancer mechanisms of action. Initially, LDM was considered an antiangiogenic treatment strategy; however, in the last decade additional preclinical studies uncovered other possible mechanisms including enhancing the antitumor immune response, substantially increasing the efficacy of targeted drugs by various mechanisms, targeting a subset of chemotherapy-resistant tumor cells, and blunting host response effects found following conventional therapy. While LDM chemotherapy is currently undergoing phase III clinical evaluation, its mechanisms of action are only partially understood. Elucidating LDM's mechanisms of action will give physicians an additional major weapon to deploy in the comprehensive management of cancer.