title: Frequent central nervous system failure after clinical benefit with epidermal growth factor receptor tyrosine kinase inhibitors in Korean patients with nonsmall-cell lung cancer.
abstract: BACKGROUND
  We investigated the risk of central nervous system (CNS) failure after clinical benefit with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in Korean patients with nonsmall-cell lung cancer (NSCLC) METHODS: We retrospectively evaluated the pattern of disease progression of 287 advanced NSCLC patients who were treated with gefitinib or erlotinib. Patients whose best tumor response was complete response, partial response, or stable disease (> or =90 days) were classified into the group receiving clinical benefit with these drugs.
  
  
  RESULTS
  The clinical benefit group had a higher incidence of CNS failure as an initial progression, compared with the non-clinical benefit group (26% vs 4%; P < .001). Isolated CNS failure was also more frequent in the clinical benefit group than in the non-clinical benefit group (13% vs 1%; P < .001). In a multivariate analysis, clinical benefit with EGFR-TKIs significantly increased the risk of isolated CNS failure, with an adjusted hazard ratio of 10.9 (95% confidence interval [CI], 1.4-29.1, P = .01). In patients with isolated CNS failure, the median time from initial intracranial failure to extracranial failure was 9.9 months (95% CI, 1.9-21.9 months) and to death was 12.9 months (95% CI, 3.3-22.5 months).
  
  
  CONCLUSIONS
  The CNS was frequently the initial failure site after clinical benefit with EGFR-TKIs in Korean NSCLC patients. Patients with isolated CNS failure showed durable extracranial control after cranial progression. A role for close surveillance of the CNS during EGFR-TKI treatment or prophylactic measures appears worthy of further study in these patients.
authors.affiliation: Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Se Kyu
authors.initials: SK
authors.lastname: Kim
authors.forename: Joon
authors.initials: J
authors.lastname: Chang
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Moon
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Park
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D016543:Central Nervous System Neoplasms / Q000556:secondary*; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D015994:Incidence; D007723:Korea; D008297:Male; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib