title: METRO1: A Phase I Study of Metronomic Chemotherapy in Adults with Advanced Refractory Solid Tumors.
abstract: BACKGROUND
  The present monocentric and prospective phase 1 study evaluated the safety of a metronomic chemotherapy in refractory tumors.
  
  
  METHODS
  Patients with advanced solid cancer refractory to standard therapy received a combination of low-dose vinorelbine, cyclophosphamide and interferon-alpha. A dose escalation model with 3 levels was planned. The primary end-point was safety and tolerability, secondary end-points were treatment continuation rate at 4 months, progression-free survival (PFS), overall survival (OS), radiological assessment (MRI) of anti-angiogenic effect.
  
  
  RESULTS
  Thirty patients were enrolled. No dose-limiting toxicity was observed. All but two adverse events were toxicities of grade 1-2. Treatment continuation rate at 4 months was 6.67% (2 out of 30 patients). Median PFS and OS were 1.6 and 6.1 months. Exploratory MRI analyses related to anti-angiogenic effect did not show any relevant modification.
  
  
  CONCLUSIONS
  This combination of metronomic chemotherapy is well-tolerated and deserves to be deeply explored in refractory solid tumors.
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France Aix-Marseille Université, Marseille, France launays@ipc.unicancer.fr.
authors.forename: Simon
authors.initials: S
authors.lastname: Launay
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France Aix-Marseille Université, Marseille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Sabatier
authors.affiliation: Department of Radiology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Brunelle
authors.affiliation: Department of Clinical Research and Innovation, Methodology and Biostatistics Unit, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Tarpin
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Viret
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Gwanaelle
authors.initials: G
authors.lastname: Gravis
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Cappiello
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Provansal
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Extra
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France Aix-Marseille Université, Marseille, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France Aix-Marseille Université, Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.affiliation: Department of Oncology, Institut Paoli-Calmettes, Marseille, France Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France Aix-Marseille Université, Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Goncalves
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D020533:Angiogenesis Inhibitors
keywords: DCE-MRI; Phase I; angiogenesis; metronomic chemotherapy