title: Lessons from the Fourth Metronomic and Anti-angiogenic Therapy Meeting, 24-25 June 2014, Milan.
abstract: The Fourth Metronomic and Anti-angiogenic Therapy Meeting was held in Milan 24-25 June 2014. The meeting was a true translational meeting where researchers and clinicians shared their results, experiences, and insights in order to continue gathering useful evidence on metronomic approaches. Several speakers emphasised that exact mechanisms of action, best timing, and optimal dosage are still not well understood and that the field would learn a lot from ancillary studies performed during the clinical trials of metronomic chemotherapies. From the pre-clinical side, new research findings indicate additional possible mechanisms of actions of metronomic schedule on the immune and blood vessel compartments of the tumour micro-environment. New clinical results of metronomic chemotherapy were presented in particular in paediatric cancers [especially neuroblastoma and central nervous system (CNS) tumours], in angiosarcoma (together with beta-blockers), in hepatocellular carcinoma, in prostate cancer, and in breast cancer. The use of repurposed drugs such as metformin, celecoxib, or valproic acid in the metronomic regimen was reported and highlighted the potential of other candidate drugs to be repurposed. The clinical experiences from low- and middle-income countries with affordable regimens gave very encouraging results which will allow more patients to be effectively treated in economies where new drugs are not accessible. Looking at the impact of metronomic approaches that have been shown to be effective, it was admitted that those approaches were rarely used in clinical practice, in part because of the absence of commercial interest for companies. However, performing well-designed clinical trials of metronomic and repurposing approaches demonstrating substantial improvement, especially in populations with the greatest unmet needs, may be an easier solution than addressing the financial issue. Metronomics should always be seen as a chance to come up with new innovative affordable approaches and not as a cheap rescue strategy.
authors.affiliation: Anticancer Fund, Strombeek-Bever B1853, Belgium.
authors.forename: Gauthier
authors.initials: G
authors.lastname: Bouche
authors.affiliation: Metronomics Global Health Initiative; Aix Marseille Université, Inserm, CRO2 UMR_S 911; & Paediatric Haematology and Oncology Department, Children's Hospital of La Timone, Marseille 13005, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.affiliation: Tata Memorial Centre, Mumbai 400012, India.
authors.forename: Shripad
authors.initials: S
authors.lastname: Banavali
authors.affiliation: Department of Paediatric Oncology, University of Cologne D50924, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Azienda Ospedaliera Spedali Civili, Brescia 25123, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.affiliation: Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, via Roma 55, Pisa 56126, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Bocci
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine University Hospital S. Orsola-Malpighi Bologna, 40138, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Brandi
authors.affiliation: Molecular Medicine Programme, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Cavallaro
authors.affiliation: Medical Oncology Department, Brindisi 72100, Italy.
authors.forename: Saviero
authors.initials: S
authors.lastname: Cinieri
authors.affiliation: Division of Medical Senology, European Institute of Oncology, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.affiliation: Division of Experimental Therapeutics, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, via Roma 55, Pisa 56126, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Di Desidero
authors.affiliation: Cancer Institute 'I. Chiricuta', Cluj-Napoca 400015, Romania.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Eniu
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Unit, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto M4N 3M5, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Kerbel
authors.affiliation: Nature Reviews Clinical Oncology, London N1 9XW, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hutchinson
authors.affiliation: Department of Mathematics and Statistics, Southern Illinois University, Edwardsville, IL 62026, USA.
authors.forename: Urszula
authors.initials: U
authors.lastname: Ledzewicz
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Munzone
authors.affiliation: Tumour Biology and Targeting Programme, Children's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Randwick 2031, Australia; Metronomics Global Health Initiative, Marseille 13005, France; & Centre for Research in Oncobiology and Oncopharmacology, INSERM UMR911, Marseille 13005, France.
authors.forename: Eddy
authors.initials: E
authors.lastname: Pasquier
authors.affiliation: Jefa Sección Oncología Experimental, Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, 2000, Argentina.
authors.forename: O
authors.initials: O
authors.lastname: Graciela Scharovsky
authors.affiliation: Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Shaked
authors.affiliation: Department of Pediatric Oncology, Masaryk University School of Medicine and University Hospital, Brno, Cernopolni 9 Brno 613 00, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Stěrba
authors.affiliation: INSERM U1040, Université de Montpellier 1, UFR Médecine, Montpellier 34295, France & Institute for Regenerative Medicine and Biotherapy (IRMB), CHU Montpellier, Montpellier 34295, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Villalba
authors.affiliation: Laboratory of Haematology-Oncology, European Institute of Oncology, Milan 20141, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
keywords: adult; anti-angiogenesis; cancer; child; drug repurposing; metronomic chemotherapy; pharmacoeconomics