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: Loïc Lebellec, Sébastien Aubert, Fahed Zaïri, Thomas Ryckewaert, Bruno Chauffert, Nicolas Penel
• Journal: Critical reviews in oncology/hematology (Crit Rev Oncol Hematol) Vol. 95 Issue 1 Pg. 125-31 (Jul 2015) ISSN: 1879-0461 [Electronic] Netherlands
• PMID: 25682222 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Vascular Endothelial Growth Factor A
• Imatinib Mesylate
• EGFR protein, human
• ErbB Receptors
• Proto-Oncogene Proteins c-kit
• Receptors, Platelet-Derived Growth Factor

Topics

• Antineoplastic Agents (therapeutic use)
• Bone Neoplasms (drug therapy, metabolism, pathology)
• Bone and Bones (drug effects, metabolism, pathology)
• Chordoma (drug therapy, metabolism, pathology)
• ErbB Receptors (metabolism)
• Humans
• Imatinib Mesylate (therapeutic use)
• Molecular Targeted Therapy (methods)
• Neoplasm Metastasis (drug therapy, pathology)
• Protein Kinase Inhibitors (therapeutic use)
• Proto-Oncogene Proteins c-kit (metabolism)
• Receptors, Platelet-Derived Growth Factor (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)