TY - JOUR
T1 - Actualités pharmacologiques - Le crizotinib (Xalkori®)
AU - Vassal, G.
AU - Schleiermacher, G.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Crizotinib is a targeted therapy agent, which has been approved in adults for treatment of non-small lung cancer with an EML4-ALK translocation. It is a tyrosine kinase inhibitor, which targets the genes ALK, MET, ROS1 and RON. These genes are also altered in several pediatric malignancies: a translocation of ALK is observed in anaplastic large-cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMT), whereas activating mutations and amplifications of ALK are observed in neuroblastoma, and overexpression of ALK is observed in rhabdomyosarcoma. MET can be amplified in hepatoblastoma. The recommended dose of crizotinib in children has been determined in a phase I study which has also shown anti-tumor effects especially in ALCL. The AcSé program of the French National Cancer Institute is now evaluating the efficacy of crizotinib in adult and pediatric cancers presenting with an alteration of ALK, MET or ROS1. In order to guarantee children's safety and in order to enable a satisfactory evaluation of the indication of crizotinib in pediatric malignancies, this drug should only be prescribed within the framework of a clinical trial.
AB - Crizotinib is a targeted therapy agent, which has been approved in adults for treatment of non-small lung cancer with an EML4-ALK translocation. It is a tyrosine kinase inhibitor, which targets the genes ALK, MET, ROS1 and RON. These genes are also altered in several pediatric malignancies: a translocation of ALK is observed in anaplastic large-cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMT), whereas activating mutations and amplifications of ALK are observed in neuroblastoma, and overexpression of ALK is observed in rhabdomyosarcoma. MET can be amplified in hepatoblastoma. The recommended dose of crizotinib in children has been determined in a phase I study which has also shown anti-tumor effects especially in ALCL. The AcSé program of the French National Cancer Institute is now evaluating the efficacy of crizotinib in adult and pediatric cancers presenting with an alteration of ALK, MET or ROS1. In order to guarantee children's safety and in order to enable a satisfactory evaluation of the indication of crizotinib in pediatric malignancies, this drug should only be prescribed within the framework of a clinical trial.
KW - Crizotinib
KW - Genetic alteration
KW - Pediatric drug development
KW - Predictive marker
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85018836624&partnerID=8YFLogxK
U2 - 10.1016/j.oncohp.2014.01.004
DO - 10.1016/j.oncohp.2014.01.004
M3 - Article
AN - SCOPUS:85018836624
SN - 2213-4670
VL - 2
SP - 46
EP - 53
JO - Revue d'Oncologie Hematologie Pediatrique
JF - Revue d'Oncologie Hematologie Pediatrique
IS - 1
ER -