title: Metronomic chemotherapy and immunotherapy in cancer treatment.
abstract: Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan; Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: wenfangcheng@yahoo.com.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
mesh_terms: D059250:Administration, Metronomic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome; D019139:Tumor Escape / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007155:Immunologic Factors
keywords: Cancer therapy; Immunotherapy; Metronomic chemotherapy