Metronomic chemotherapy in hematological malignancies

Abstract

Targeting tumor microenvironment and angiogenesis is a novel therapeutic strategy in hematological malignancies. The antiangiogenic effects of chemotherapeutic agents can be optimized when administered metronomically, by providing low doses of chemotherapeutic drugs on a continuous schedule without extended drug-free intervals. Metronomic chemotherapy preferentially targets endothelial cells of the growing tumor neovasculature instead of tumor cells themselves and therefore can be particularly effective against multidrug-resistant tumors. Metronomic therapy may further enhance immune response by modulating antitumor NK/T-cell functions. The past decade saw an increasing appreciation of the pathogenic roles that tumor angiogenesis plays in hematological malignancies including leukemias, lymphomas, and multiple myeloma. Experimentation with a variety of antiangiogenesis modalities has shown encouraging efficacy with metronomic chemotherapy in these disease categories, with generally low toxicity and cost. With the growing availability of the target-specific biological agents, some of which are specific for antiangiogenesis, it is conceivable that metronomic chemotherapy, either alone or in combination with biologics, has therapeutic potential in frontline and maintenance setting, in addition to its traditional role of salvage option for relapsed diseases in hematological malignancies.