title: Molecular targeted therapies in advanced or metastatic chordoma patients: facts and hypotheses.
abstract: Chordomas, derived from undifferentiated notochordal remnants, represent less than 4% of bone primary tumors. Despite surgery followed by radiotherapy, local and metastatic relapses are frequent. In case of locally advanced or metastatic chordomas, medical treatment is frequently discussed. While chemotherapy is ineffective, it would appear that some molecular targeted therapies, in particular imatinib, could slow down the tumor growth in case-reports, retrospective series, and phase I or II trials. Nineteen publications, between January 1990 and September 2014, have been found describing the activity of these targeted therapies. A systematic analysis of these publications shows that the best objective response with targeted therapies was stabilization in 52 to 69% of chordomas. Given the indolent course of advanced chordoma and because of the absence of randomized trial, the level of evidence to treat chordomas with molecular therapy is low (level III), whatever the drug. Furthermore, we could not draw firm conclusion on the activity of imatinib. Other putative targets have also been described. Therefore, further clinical trials are expected, especially with these targets. Nevertheless, it seems essential, in those future studies, to consider the naturally slow course of the disease.
authors: Medical Oncology Department, Centre Oscar Lambret, Lille, France.
authors: Loïc
authors: L
authors: Lebellec
authors: Department of Pathology, University Hospital, CHRU & Lille II University, Lille, France.
authors: Sébastien
authors: S
authors: Aubert
authors: Department of Neurosurgery, Department of Pathology, University Hospital, CHRU & Lille II University, Lille, France.
authors: Fahed
authors: F
authors: Zaïri
authors: Medical Oncology Department, Centre Oscar Lambret, Lille, France.
authors: Thomas
authors: T
authors: Ryckewaert
authors: Department of Medical Oncology, Amiens University Hospital, Amiens University, Amiens, France.
authors: Bruno
authors: B
authors: Chauffert
authors: Medical Oncology Department, Centre Oscar Lambret, Lille, France; Research Unit (EA2694), Medical School University, Lille-Nord de France University, Lille, France. Electronic address: scientifique@o-lambret.fr.
authors: Nicolas
authors: N
authors: Penel
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002817:Chordoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068877:Imatinib Mesylate; C512478:EGFR protein, human; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor
keywords: Chordomas; Imatinib; Molecular targeted therapies; Review