title: Cerebrospinal fluid concentration of erlotinib and its active metabolite OSI-420 in patients with central nervous system metastases of non-small cell lung cancer.
abstract: BACKGROUND
  Although there have been several reports in which central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) were improved by erlotinib, cerebrospinal fluid (CSF) penetration of erlotinib in such patients has not been reported. We investigated CSF concentrations of erlotinib and its active metabolite OSI-420.
  
  
  METHODS
  We administered 150 mg erlotinib daily to four patients with NSCLC who had CNS metastases, and we investigated plasma pharmacokinetics of erlotinib and OSI-420 on days 1 and 8. In addition, we measured the concentrations of erlotinib and OSI-420 in CSF just before administration of erlotinib on day 8.
  
  
  RESULTS
  In all cases except for one case, plasma pharmacokinetics data on day 8 were similar to those previously reported. The mean +/- SD CSF concentrations of erlotinib and OSI-420 were 54 +/- 30 ng/ml and 10.8 +/- 8.2 ng/ml, respectively. The mean +/- SD CSF penetration rates of erlotinib and OSI-420 were 5.1% +/- 1.9% and 5.8% +/- 3.6%, respectively. CSF concentrations of erlotinib exceeded median inhibitory concentration (IC50) of erlotinib in intact tumor cells with wild-type epidermal growth factor receptor gene.
  
  
  CONCLUSIONS
  The CSF penetrations of erlotinib and OSI-420 in patients with NSCLC who had CNS metastases were approximately 5.1% and 5.8%, respectively. This indicates that erlotinib can become a treatment option for CNS metastases of NSCLC.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Togashi
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Masago
authors.forename: Masahide
authors.initials: M
authors.lastname: Fukudo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Terada
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Irisa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sakamori
authors.forename: Young Hak
authors.initials: YH
authors.lastname: Kim
authors.forename: Tadashi
authors.initials: T
authors.lastname: Mio
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inui
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000230:Adenocarcinoma / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000494:pharmacology; D011799:Quinazolines / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000494:pharmacology; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: C487471:OSI-420; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors