Metronomic chemotherapy in non-small-cell lung cancer

Abstract

Metronomic chemotherapy is an alternative approach for the administration of systemic chemotherapy that consists of the administration of low doses of a cytotoxic regimen without any interruptions. Endothelial cells of the tumor blood vessels are rapidly proliferating cells that could be affected with the metronomic use of chemotherapy. Indeed, it is strongly believed that this strategy inhibits vascular angiogenesis and subsequently tumor growth mainly through modulating the cancer microenvironment with favorable toxicity profile. In addition, immune suppression is a reality among the vast majority of cancer patients. T regulatory cells (Tregs) are the main representative of suppressive cells, and their increased expression in cancer has been associated with worse prognosis and tumor progression. Low doses of chemotherapeutic agents have been proven capable to restore the normal immune system function through the elimination of immune suppressive cells. Numerous studies have investigated the efficacy of metronomic strategy in NSCLC patients with very promising results. Several chemotherapeutic agents, such as vinorelbine, gemcitabine, cyclophosphamide, and docetaxel, have been tested as monotherapy or in combination with other drugs. Whether other mechanisms, such as tumor dormancy, are also involved in the effectiveness of metronomic administration of chemotherapy or if it is superior to conventional chemotherapy remains questionable, and further investigation is required.