title: BIBF 1120/ nintedanib : a new triple angiokinase inhibitor-directed therapy in patients with non-small cell lung cancer.
abstract: BACKGROUND
  Several new targeted agents with anti-angiogenic properties have been developed recently, including vandetanib, sunitinib, sorafenib, bevacizumab and others. Tumor development, progression, metastasis are strongly linked to angiogenesis. Targeted agents like bevacizumab, a monoclonal antibody which targets VEGF, have been fully developed in several solid tumors. These new agents strongly advocate that targeting angiogenesis is one of the best approaches for cancer therapy.
  
  
  METHODS
  Those agents that target additional pro-angiogenic intracellular signaling pathways beyond VEGF signaling have also the potential to contribute to anticancer therapies. The authors present here nintedanib (BIBF 1120), a triple angiokinase inhibitor. It targets not only VEGFRs, but also FGFR and PDGFR. All the available clinical information regarding Phase I - II trials and the toxicity and efficacy of BIBF 1120 both as single agent and in combination with cytotoxic agents in non-small cell lung cancer (NSCLC) is reviewed and discussed here.
  
  
  CONCLUSIONS
  Up till now, Phase I and II trials with nintedanib showed an improvement for survival of advanced NSCLC patients. Tolerability profile seems to be acceptable in these clinical trials. However, Phase III trials are mandatory to translate these findings into clinical practice. The research for predictive biomarkers could improve the success of these anti-angiogenic agents.
authors.affiliation: Antwerp University Hospital, Oncology Department, Phase I - Early Clinical Trials Unit, Edegem, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bronte
authors.forename: Edgardo S
authors.initials: ES
authors.lastname: Santos
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Papadimitriou
authors.forename: Lucio
authors.initials: L
authors.lastname: Buffoni
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Meerbeeck
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C530716:nintedanib