title: Metronomic chemotherapy from rationale to clinical studies: a dream or reality?
abstract: Metronomic chemotherapy (MC) refers to the close administration of a chemotherapeutic drug for a long time with no extended drug-free breaks. It was developed to overcome drug resistance, partly by shifting the therapeutic target from tumor cells to the tumor vasculature, with less toxicity. Because of this peculiar way of administration, MC can be viewed as a form of long-term 'maintenance' treatment, and can be integrated with standard and conventional chemotherapy in a "chemo-switching" strategy. Additional mechanisms are involved in its antitumor activity, such as activation of immunity, induction of tumor dormancy, chemotherapy-driven dependency of cancer cells, and the '4D effect'. In this paper we report the most important studies that have analyzed these processes. In fact, a number of preclinical and clinical studies in solid tumors as well as in multiple myeloma, have been reported regarding several chemotherapy drugs which have been proposed with a metronomic schedule: vinorelbine, cyclophosphamide, capecitabine, methotrexate, bevacizumab, etoposide, gemcitabine, sorafenib, everolimus and temozolomide. The results of these studies have been sometimes conflicting, highlighting the need to develop reliable tools for patient selection and stratification. However, a more precise evaluation of MC strategies with the ongoing randomized phase II/III clinical is fundamental, because of the strict correlation of this approach with translational research and target therapy. Moreover, because of the low toxicity of MC, these studies will also help to better evaluate the clinical benefit of this treatment, with a special focus on elderly and low performance status patients.
authors: Medical Oncology Unit, Hospital Moscati, Taranto, Italy.
authors: Antonio
authors: A
authors: Gnoni
authors: Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy.
authors: Nicola
authors: N
authors: Silvestris
authors: Medical Oncology Unit, Hospital Moscati, Taranto, Italy.
authors: Antonella
authors: A
authors: Licchetta
authors: Medical Oncology Unit, University Campus Biomedico, Roma, Italy.
authors: Daniele
authors: D
authors: Santini
authors: Department of Medical Oncoloy, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
authors: Mario
authors: M
authors: Scartozzi
authors: Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors: Roberto
authors: R
authors: Ria
authors: Medical Oncology Unit, Hospital Moscati, Taranto, Italy.
authors: Salvatore
authors: S
authors: Pisconti
authors: Medical Oncology Unit, Hospital of Treviglio, Treviglio, Italy.
authors: Fausto
authors: F
authors: Petrelli
authors: Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors: Angelo
authors: A
authors: Vacca
authors: Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy. Electronic address: vitolorusso@me.com.
authors: Vito
authors: V
authors: Lorusso
mesh_terms: D059250:Administration, Metronomic; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007109:Immunity / Q000187:drug effects; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: Angiogenesis; Bevacizumab; Chemo-switching; Cyclophosphamide; Immunity; Maintenance; Metronomic chemotherapy; Toxicity