TITLE:
Crizotinib in non-small cell lung cancer
AUTHORS:
Nawfel Mellas, Fatimzahra Hijri, Zineb Benbrahim, Omar El Mesbahi, Nabil Ismaili
KEYWORDS:
NSCLC; Crizotinib; Metastatic NSCLC; ALK; Chemotherapy
JOURNAL NAME:
Modern Chemotherapy,
Vol.3 No.1,
January
24,
2014
ABSTRACT: Chemotherapy and
targeted therapy remain the cornerstone of
treatment of locally advanced and metastatic non-small cells lung cancer
(NSCLC). Given the intrinsic chemoresistance of tumor cells, new treatment
options have been developped. The knowledge of the molecular mechanisms of
tumor biology, and signal transduction pathways activating cancer cells led to
the identification of a new targeted therapy such as Crizotinib. The small
molecule Crizotinib is a selective inhibitor of the receptor tyrosine kinase
ALK (anaplastic lymphoma kinase) and its oncogenic variants (ALK fusion gene
and some mutations of ALK). Phases I and II trials showed the efficacy of
Crizotinib in the treatment of locally advanced and metastatic NSCLC expressing
ALK. Thereafter, randomized Phase III trial confirmed the significant
superiority of Crizotinib versus standard chemotherapy in terms of progression
free survival and objective response with good tolerance; therefore, it has
been approved by the Food and Drug Administration (FDA) as the standard
treatment for locally advanced and metastatic ALK-positive NSCLC.