title: Metronomic chemotherapy for cancer treatment: a decade of clinical studies.
abstract: OBJECTIVE
  Over the past few years, more and more new selective molecules directed against specific cellular targets have become available for cancer therapy, leading to impressive improvements. In this evolving scenario, a new way of delivering older cytotoxic drugs has also been developing. Many studies demonstrated that several cytotoxic drugs have antiangiogenic properties if administered frequently and at lower doses compared with standard schedules containing maximal tolerated doses (MTD). Such a new strategy, named metronomic chemotherapy, focuses on a different target: the slowly proliferating tumour endothelial cells. About 10 years ago, metronomic chemotherapy was firstly enunciated and hereafter many clinical experiences were published related to almost any cancer disease. This review analyses available studies dealing with metronomic chemotherapy and its combination with several targeted agents in solid tumours.
  
  
  METHODS
  A computerized literature search of MEDLINE was performed using the following search terms: metronomic OR "continuous low dose" AND chemotherapy AND cancer OR solid tumours.
  
  
  RESULTS
  Satisfactory results have been achieved in diverse tumour types, such as breast and prostate cancer or paediatric sarcomas. Moreover, many studies have reported that metronomic chemotherapy determined minimal toxicity compared to MTD chemotherapy. Overall, published series on metronomic schedules are very heterogeneous often reporting on retrospective data, while only very few studies were randomized trials. These limitations still prevent to draw definitive conclusions in diverse tumour types.
  
  
  CONCLUSIONS
  Large well-designed studies are eagerly awaited for confirming the promises of metronomic schedules and their combinations with targeted molecules.
authors.affiliation: Department of Oncology, Faculty of Medicine and Psychology, Sapienza University, Sant' Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy. adriana.romiti@tin.it
authors.forename: Adriana
authors.initials: A
authors.lastname: Romiti
authors.forename: M Christina
authors.initials: MC
authors.lastname: Cox
authors.forename: Ida
authors.initials: I
authors.lastname: Sarcina
authors.forename: Roberta
authors.initials: R
authors.lastname: Di Rocco
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Antonio
authors.forename: Viola
authors.initials: V
authors.lastname: Barucca
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
mesh_terms: D059250:Administration, Metronomic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D019317:Evidence-Based Medicine; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents