title: Rapid response of brain metastases to alectinib in a patient with non-small-cell lung cancer resistant to crizotinib.
abstract: Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor. Alectinib is a highly selective, next-generation ALK inhibitor, and both preclinical and clinical studies have indicated that alectinib is also effective in crizotinib-resistant tumors. A recent in vitro study demonstrated significant antitumor activity of alectinib for brain metastases using mouse models of ALK-positive non-small-cell lung cancer. In this paper, we report a first case alectinib was highly effective against brain metastases refractory to crizotinib. Further investigation of alectinib in this setting would be particularly valuable.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ajimizu
authors.forename: Young Hak
authors.initials: YH
authors.lastname: Kim
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D002227:Carbazoles / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010880:Piperidines / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C582670:alectinib