title: Clinical impact of continued crizotinib administration after isolated central nervous system progression in patients with lung cancer positive for ALK rearrangement.
abstract: BACKGROUND
  Although crizotinib manifests marked antitumor activity in individuals with non-small-cell lung cancer positive for ALK abnormalities, all treated patients ultimately develop resistance to this drug. The central nervous system (CNS) is a frequent site of disease progression in such patients, with palliative radiotherapy usually being administered for the CNS metastasis. However, subsequent chemotherapy has not been optimized in these patients.
  
  
  METHODS
  We retrospectively evaluated the continuation of crizotinib treatment after radiotherapy for isolated CNS progression in ALK-rearrangement-positive non-small-cell lung cancer patients.
  
  
  RESULTS
  Among 21 ALK-rearrangement-positive patients treated with crizotinib, seven individuals resumed daily crizotinib administration after the completion of radiotherapy for isolated CNS failure. All these patients continued to receive crizotinib for at least 4 months after radiotherapy without disease progression. One patient experienced a recurrent isolated CNS failure during the second period of crizotinib administration but subsequently resumed crizotinib treatment again for at least 8.5 months after another application of radiotherapy.
  
  
  CONCLUSIONS
  Development of isolated CNS metastasis is emerging as a clinical concern for patients treated with crizotinib. Our data suggest that continued administration of crizotinib after radiotherapy for isolated CNS progression is a potential treatment option for such patients.
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Ohno-higashi, Osaka-Sayama, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D000077547:Crizotinib; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D016634:Radiosurgery; D011878:Radiotherapy; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases